Title

Title:The prevalence of Community-Associated Methicillin-Resistant Staphylococcus aureus in Jeddah population.

By:
Mohammed Saeed AbdohMaster Degree Thesis Presented toKing Abdul Aziz University
Medical Laboratory Technology College
Graduate Board
in Partial Fulfillment of the
Requirements for the Master Degree
of Medical Laboratory Technology
Table of Contents
TOC o “1-3” h z u 1.introduction: PAGEREF _Toc525512921 h 61.1.Staphylococcus aureus general description: PAGEREF _Toc525512922 h 81.2.History of S. aureus: PAGEREF _Toc525512923 h 81.3.S. aureus Economical burden: PAGEREF _Toc525512924 h 81.4.S. aureus genome: PAGEREF _Toc525512925 h 91.5.Pathogenesis and virulence factors: PAGEREF _Toc525512926 h 101.6.Antibiotic resistance: PAGEREF _Toc525512927 h 121.7.Methicillin-resistant Staphylococcus aureus (MRSA): PAGEREF _Toc525512928 h 151.7.1Emerging methicillin resistance: PAGEREF _Toc525512929 h 151.7.2Mechanism of Methicillin-resistance: PAGEREF _Toc525512930 h 171.7.3Staphylococcal cassette chromosome mec (SCCmec) elements: PAGEREF _Toc525512931 h 181.7.4Epidemiology of MRSA in hospital: PAGEREF _Toc525512932 h 191.7.5Risk factors associated with nosocomial MRSA: PAGEREF _Toc525512933 h 201.7.6Epidemiology of MRSA in the community: PAGEREF _Toc525512934 h 221.7.7 Treatment and control of MRSA: PAGEREF _Toc525512935 h 231.8The typing of MRSA: PAGEREF _Toc525512936 h 251.8.1Mechanism of genetic variability of bacterial genome: PAGEREF _Toc525512937 h 251.8.2Phenotyping methods: PAGEREF _Toc525512938 h 261.8.3Genotyping methods: PAGEREF _Toc525512939 h 271.8.4Antimicrobial susceptibility pattern: PAGEREF _Toc525512940 h 272.General Material and Methods: PAGEREF _Toc525512941 h 302.1.Chemical and Reagents: PAGEREF _Toc525512942 h 302.2.Preparation of buffers and solutions : PAGEREF _Toc525512943 h 302.3.Chelex preparation: PAGEREF _Toc525512944 h 302.4.TAE buffer preparation for gel electrophoresis: PAGEREF _Toc525512945 h 302.4.1.TAE buffer 50 X preparation: PAGEREF _Toc525512946 h 302.4.2.TAE buffer 1 X preparation: PAGEREF _Toc525512947 h 302.5.Culture Medium: PAGEREF _Toc525512948 h 312.6.Growth and storage of strains: PAGEREF _Toc525512949 h 312.6.1.Sources of standard staphylococci strains: PAGEREF _Toc525512950 h 312.6.2.Sources of Nasal swab isolates: PAGEREF _Toc525512951 h 312.6.3.Inclusion and exclusion criteria: PAGEREF _Toc525512952 h 312.6.4.Sample collection methods: PAGEREF _Toc525512953 h 322.7.Identification of MRSA from collected samples: PAGEREF _Toc525512954 h 322.7.1.Chromogenic Agar MRSA Screening: PAGEREF _Toc525512955 h 322.7.2.Subculture on Blood Agar and Glycerol: PAGEREF _Toc525512956 h 332.7.3.Latex slide agglutination Coagulase Screening Test: PAGEREF _Toc525512957 h 332.7.4.Extraction of chromosomal DNA from MRSA: PAGEREF _Toc525512958 h 332.7.4.1 Rapid Extraction of chromosomal DNA using the boiling method for conventional Polymerase Chain Reaction (PCR): PAGEREF _Toc525512959 h 332.7.4.2 Extraction of chromosomal DNA from MRSA for Sma I Multilplex PCR: PAGEREF _Toc525512960 h 342.8.Molecular typing of MRSA isolates: PAGEREF _Toc525512961 h 342.8.1.Polymerase Chain Reaction ( PCR): PAGEREF _Toc525512962 h 342.8.2. Detection of the mecA methicillin-resistance gene: PAGEREF _Toc525512963 h 362.8.3. Detection of coagulase (coa) gene: PAGEREF _Toc525512964 h 362.8.4. Detection of the Panton-Valentin leukocidin (lukS-PV) gene: PAGEREF _Toc525512965 h 362.8.5.Pulse field gel Electrophoresis : PAGEREF _Toc525512966 h 362.8.6.Sma I Multilplex PCR: PAGEREF _Toc525512967 h 373.Results PAGEREF _Toc525512968 h 374.Data Analysis PAGEREF _Toc525512969 h 375.Discussion PAGEREF _Toc525512970 h 376.Conclusion PAGEREF _Toc525512971 h 377.abstract PAGEREF _Toc525512972 h 378. PAGEREF _Toc525512973 h 37
List of Figures
TOC f f h z c “Figure” Figure 1-Staphylococcus aureus Drug Resistance and Epidemics. PAGEREF _Toc524055475 h 12Figure 2- The principle mechanism of penicillin resistance to ?-lactamases. PAGEREF _Toc524055476 h 13Figure 3: The proportion of isolates of Staphylococcus aureus from blood culture that are methicillin resistant, England and Wales (Johnson et al., 2005). PAGEREF _Toc524055477 h 18Figure 4: Number of deaths involving MRSA and S. aureus,Wales, deaths registered in 1993 to 2014 (Source: Office for National Statistics) PAGEREF _Toc524055478 h 20Figure 5: Age-standardized rates for deaths involving MRSA and S. aureus, Wales, deaths registered in 1993 to 2014 (Source: Office for National Statistics PAGEREF _Toc524055479 h 21
List of Tables
TOC h z c “Table” Table 1: The sequenced genomes of S.aureus PAGEREF _Toc524055492 h 16Table 2: SCCmec types (adapted from IWG-SCC (2009). PAGEREF _Toc524055493 h 19Table 3: Table 3: Components of PCR reaction Mixture PAGEREF _Toc524055494 h 34Table 4: PCR reaction Conditions PAGEREF _Toc524055495 h 34
Chapter One
introduction:Staphylococcus aureus (S.aurues) may cause several infections with considerable morbidity and mortality in healthy and immunocompromised hosts ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “ISSN” : “1678-9849 (Electronic)”, “PMID” : “23563822”, “abstract” : “INTRODUCTION: \t\t\t\t\tMethicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen commonly associated with nosocomial infections. However, it has also been associated with community-acquired skin and soft tissue infections (CA-MRSA). There are few data on the identification and prevalence of CA-MRSA infections in Brazil. \t\t\t\t\t\t\t\t\t\t\t\t\tMETHODS: \t\t\t\t\tThis is a cross-sectional study of 104 patients with community-acquired skin infections attending two health care centers in Porto Alegre, southern Brazil. MRSA isolates were characterized by molecular methods, including detection of the mecA gene by PCR, gene SCCmec typing, Panton-Valentine leukocidin (PVL) detection, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). \t\t\t\t\t\t\t\t\t\t\t\t\tRESULTS:\t\t\t\t\t From the 104 samples, 58 Staphylococcus aureus isolates were obtained, of which five (8.6%) had a CA-MRSA-resistant profile. All five isolates had the mecA gene and amplified to SCCmec type IV. Analysis of chromosomal DNA by PFGE revealed the presence of two clusters related to international clones (OSPC and USA 300), with a Dice similarity coefficient >80%. The study was complemented by MLST, which detected three different strains: ST30, ST8, and ST45, the latter not presenting any relation with the clones compared in PFGE. \t\t\t\t\t\t\t\t\t\t\t\t\tCONCLUSIONS: \t\t\t\t\tThe presence of CA-MRSA reveals an important change in the epidemiology of this pathogen and adds new elements to the knowledge of the molecular biology of infections by MRSA with SCCmec type IV in southern Brazil.”, “author” : { “dropping-particle” : “”, “family” : “Gelatti”, “given” : “Luciane Cristina”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Bonamigo”, “given” : “Renan Rangel”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Inoue”, “given” : “Fernanda Matsiko”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “do”, “family” : “Carmo”, “given” : “Mirian Silva”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Becker”, “given” : “Ana Paula”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Castrucci”, “given” : “Fernanda Marques da Silva”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pignatari”, “given” : “Antu00f4nio Carlos Campos”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “d' Azevedo”, “given” : “Pedro Alves”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Revista da Sociedade Brasileira de Medicina Tropical”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2013” }, “page” : “34-38”, “title” : “Community-acquired methicillin-resistant Staphylococcus aureus carrying SCCmec type IV in southern Brazil”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=3eedfa59-af13-44f2-8908-c1c3e25e8389” } , “mendeley” : { “formattedCitation” : “(Gelatti et al. 2013)”, “plainTextFormattedCitation” : “(Gelatti et al. 2013)”, “previouslyFormattedCitation” : “(Gelatti et al. 2013)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Gelatti et al. 2013). S.aureus causes far reaching human illness extending from soft skin diseases to deadly necrotizing pneumonia and sepsis ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1086/509506”, “ISBN” : “0022-1899 (Print)”, “ISSN” : “0022-1899”, “PMID” : “17109350”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) remains a major problem in hospitals, and it is now spreading in the community. A single toxin, Panton-Valentine leukocidin (PVL), has been linked by epidemiological studies to community-associated MRSA (CA-MRSA) disease. However, the role that PVL plays in the pathogenesis of CA-MRSA has not been tested directly. To that end, we used mouse infection models to compare the virulence of PVL-positive with that of PVL-negative CA-MRSA representing the leading disease-causing strains. Unexpectedly, strains lacking PVL were as virulent in mouse sepsis and abscess models as those containing the leukotoxin. Isogenic PVL-negative (lukS/F-PV knockout) strains of USA300 and USA400 were as lethal as wild-type strains in a sepsis model, and they caused comparable skin disease. Moreover, lysis of human neutrophils and pathogen survival after phagocytosis were similar between wild-type and mutant strains. Although the toxin may be a highly linked epidemiological marker for CA-MRSA strains, we conclude that PVL is not the major virulence determinant of CA-MRSA.”, “author” : { “dropping-particle” : “”, “family” : “Voyich”, “given” : “Jovanka M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Otto”, “given” : “Michael”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Mathema”, “given” : “Barun”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Braughton”, “given” : “Kevin R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Whitney”, “given” : “Adeline R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Welty”, “given” : “Diane”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Long”, “given” : “R Daniel”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dorward”, “given” : “David W”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gardner”, “given” : “Donald J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lina”, “given” : “Gu00e9rard”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kreiswirth”, “given” : “Barry N”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “DeLeo”, “given” : “Frank R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Journal of infectious diseases”, “id” : “ITEM-1”, “issue” : “12”, “issued” : { “date-parts” : “2006” }, “page” : “1761-70”, “title” : “Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease?”, “type” : “article-journal”, “volume” : “194” }, “uris” : “http://www.mendeley.com/documents/?uuid=d27c9303-f66d-4729-99f5-4c2537f21ccd” } , “mendeley” : { “formattedCitation” : “(Voyich et al. 2006)”, “plainTextFormattedCitation” : “(Voyich et al. 2006)”, “previouslyFormattedCitation” : “(Voyich et al. 2006)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Voyich et al. 2006). This superbug has ended up progressively to be safe from been affected by -lactam antibiotics, and methicillin-resistant S. aureus (MRSA) is a driving cause of hospital-acquired diseases ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1086/509506”, “ISBN” : “0022-1899 (Print)”, “ISSN” : “0022-1899”, “PMID” : “17109350”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) remains a major problem in hospitals, and it is now spreading in the community. A single toxin, Panton-Valentine leukocidin (PVL), has been linked by epidemiological studies to community-associated MRSA (CA-MRSA) disease. However, the role that PVL plays in the pathogenesis of CA-MRSA has not been tested directly. To that end, we used mouse infection models to compare the virulence of PVL-positive with that of PVL-negative CA-MRSA representing the leading disease-causing strains. Unexpectedly, strains lacking PVL were as virulent in mouse sepsis and abscess models as those containing the leukotoxin. Isogenic PVL-negative (lukS/F-PV knockout) strains of USA300 and USA400 were as lethal as wild-type strains in a sepsis model, and they caused comparable skin disease. Moreover, lysis of human neutrophils and pathogen survival after phagocytosis were similar between wild-type and mutant strains. Although the toxin may be a highly linked epidemiological marker for CA-MRSA strains, we conclude that PVL is not the major virulence determinant of CA-MRSA.”, “author” : { “dropping-particle” : “”, “family” : “Voyich”, “given” : “Jovanka M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Otto”, “given” : “Michael”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Mathema”, “given” : “Barun”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Braughton”, “given” : “Kevin R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Whitney”, “given” : “Adeline R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Welty”, “given” : “Diane”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Long”, “given” : “R Daniel”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dorward”, “given” : “David W”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gardner”, “given” : “Donald J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lina”, “given” : “Gu00e9rard”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kreiswirth”, “given” : “Barry N”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “DeLeo”, “given” : “Frank R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Journal of infectious diseases”, “id” : “ITEM-1”, “issue” : “12”, “issued” : { “date-parts” : “2006” }, “page” : “1761-70”, “title” : “Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease?”, “type” : “article-journal”, “volume” : “194” }, “uris” : “http://www.mendeley.com/documents/?uuid=d27c9303-f66d-4729-99f5-4c2537f21ccd” } , “mendeley” : { “formattedCitation” : “(Voyich et al. 2006)”, “plainTextFormattedCitation” : “(Voyich et al. 2006)”, “previouslyFormattedCitation” : “(Voyich et al. 2006)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Voyich et al. 2006).
MRSA, 1st recognized in the 1960s, was usually related with healthcare facilities and commonly related with serious nosocomial infection or hospital acquired infection ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “ISSN” : “1678-9849 (Electronic)”, “PMID” : “23563822”, “abstract” : “INTRODUCTION: \t\t\t\t\tMethicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen commonly associated with nosocomial infections. However, it has also been associated with community-acquired skin and soft tissue infections (CA-MRSA). There are few data on the identification and prevalence of CA-MRSA infections in Brazil. \t\t\t\t\t\t\t\t\t\t\t\t\tMETHODS: \t\t\t\t\tThis is a cross-sectional study of 104 patients with community-acquired skin infections attending two health care centers in Porto Alegre, southern Brazil. MRSA isolates were characterized by molecular methods, including detection of the mecA gene by PCR, gene SCCmec typing, Panton-Valentine leukocidin (PVL) detection, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). \t\t\t\t\t\t\t\t\t\t\t\t\tRESULTS:\t\t\t\t\t From the 104 samples, 58 Staphylococcus aureus isolates were obtained, of which five (8.6%) had a CA-MRSA-resistant profile. All five isolates had the mecA gene and amplified to SCCmec type IV. Analysis of chromosomal DNA by PFGE revealed the presence of two clusters related to international clones (OSPC and USA 300), with a Dice similarity coefficient >80%. The study was complemented by MLST, which detected three different strains: ST30, ST8, and ST45, the latter not presenting any relation with the clones compared in PFGE. \t\t\t\t\t\t\t\t\t\t\t\t\tCONCLUSIONS: \t\t\t\t\tThe presence of CA-MRSA reveals an important change in the epidemiology of this pathogen and adds new elements to the knowledge of the molecular biology of infections by MRSA with SCCmec type IV in southern Brazil.”, “author” : { “dropping-particle” : “”, “family” : “Gelatti”, “given” : “Luciane Cristina”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Bonamigo”, “given” : “Renan Rangel”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Inoue”, “given” : “Fernanda Matsiko”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “do”, “family” : “Carmo”, “given” : “Mirian Silva”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Becker”, “given” : “Ana Paula”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Castrucci”, “given” : “Fernanda Marques da Silva”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pignatari”, “given” : “Antu00f4nio Carlos Campos”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “d' Azevedo”, “given” : “Pedro Alves”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Revista da Sociedade Brasileira de Medicina Tropical”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2013” }, “page” : “34-38”, “title” : “Community-acquired methicillin-resistant Staphylococcus aureus carrying SCCmec type IV in southern Brazil”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=3eedfa59-af13-44f2-8908-c1c3e25e8389” } , “mendeley” : { “formattedCitation” : “(Gelatti et al. 2013)”, “plainTextFormattedCitation” : “(Gelatti et al. 2013)”, “previouslyFormattedCitation” : “(Gelatti et al. 2013)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Gelatti et al. 2013). Upon its prevalence which has reportedly increased in otherwise healthy patients without identified risk factors ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1155/2015/923941”, “ISSN” : “20900058”, “PMID” : “25653870”, “abstract” : “Purpose. To compare the clinical features of community-associated (CA) and healthcare-associated (HA) methicillin-resistant Staphylococcus aureus (MRSA) keratitis. Methods. Patients presenting with culture-proven MRSA keratitis between January 1, 2006, and December 31, 2010, at Chang Gung Memorial Hospital, Taiwan, were included in this study. The patients’ demographic and clinical information were reviewed retrospectively. Antibiotic susceptibility was verified using the disk diffusion method. Results. Information on 26 patients with MRSA keratitis was collected, including 12 cases of CA-MRSA and 14 cases of HA-MRSA. All MRSA isolates were susceptible to vancomycin; the only difference in drug susceptibility was that CA-MRSA isolates were more susceptible to trimethoprim/sulfamethoxazole than HA-MRSA P=.034. The most common risk factor for MRSA keratitis was ocular surface disease. No significant differences were observed between the 2 groups in terms of clinical features, treatments, and visual outcomes. Conclusion. In Taiwan, CA-MRSA rivals HA-MRSA as a critical cause of MRSA keratitis. Furthermore, CA-MRSA isolates are multidrug resistant. CA-MRSA and HA-MRSA keratitis are clinically indistinguishable, although larger studies are warranted to further evaluate this association.”, “author” : { “dropping-particle” : “”, “family” : “Hsiao”, “given” : “Ching Hsi”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ong”, “given” : “Sherine Jue”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chuang”, “given” : “Chih Chun”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ma”, “given” : “David H.K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Huang”, “given” : “Yhu Chering”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Ophthalmology”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2015” }, “title” : “A comparison of clinical features between community-associated and healthcare-associated methicillin-resistant staphylococcus aureus keratitis”, “type” : “article”, “volume” : “2015” }, “uris” : “http://www.mendeley.com/documents/?uuid=3b06be94-0ece-46dd-b39b-188613bacd54” } , “mendeley” : { “formattedCitation” : “(Hsiao et al. 2015)”, “plainTextFormattedCitation” : “(Hsiao et al. 2015)”, “previouslyFormattedCitation” : “(Hsiao et al. 2015)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Hsiao et al. 2015). Such infection is termed as community-associated MRSA (CA-MRSA), and they are clinically, microbiologically, dissimilar from hospital –acquired MRSA (HA-MRSA) ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1155/2015/923941”, “ISSN” : “20900058”, “PMID” : “25653870”, “abstract” : “Purpose. To compare the clinical features of community-associated (CA) and healthcare-associated (HA) methicillin-resistant Staphylococcus aureus (MRSA) keratitis. Methods. Patients presenting with culture-proven MRSA keratitis between January 1, 2006, and December 31, 2010, at Chang Gung Memorial Hospital, Taiwan, were included in this study. The patients’ demographic and clinical information were reviewed retrospectively. Antibiotic susceptibility was verified using the disk diffusion method. Results. Information on 26 patients with MRSA keratitis was collected, including 12 cases of CA-MRSA and 14 cases of HA-MRSA. All MRSA isolates were susceptible to vancomycin; the only difference in drug susceptibility was that CA-MRSA isolates were more susceptible to trimethoprim/sulfamethoxazole than HA-MRSA P=.034. The most common risk factor for MRSA keratitis was ocular surface disease. No significant differences were observed between the 2 groups in terms of clinical features, treatments, and visual outcomes. Conclusion. In Taiwan, CA-MRSA rivals HA-MRSA as a critical cause of MRSA keratitis. Furthermore, CA-MRSA isolates are multidrug resistant. CA-MRSA and HA-MRSA keratitis are clinically indistinguishable, although larger studies are warranted to further evaluate this association.”, “author” : { “dropping-particle” : “”, “family” : “Hsiao”, “given” : “Ching Hsi”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ong”, “given” : “Sherine Jue”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chuang”, “given” : “Chih Chun”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ma”, “given” : “David H.K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Huang”, “given” : “Yhu Chering”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Ophthalmology”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2015” }, “title” : “A comparison of clinical features between community-associated and healthcare-associated methicillin-resistant staphylococcus aureus keratitis”, “type” : “article”, “volume” : “2015” }, “uris” : “http://www.mendeley.com/documents/?uuid=3b06be94-0ece-46dd-b39b-188613bacd54” } , “mendeley” : { “formattedCitation” : “(Hsiao et al. 2015)”, “plainTextFormattedCitation” : “(Hsiao et al. 2015)”, “previouslyFormattedCitation” : “(Hsiao et al. 2015)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Hsiao et al. 2015). CA-MRSA strains primarily involve infection of the skin and soft tissues, and they occasionally cause severe infections ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1086/427148”, “ISBN” : “1537-6591; 1058-4838”, “ISSN” : “1058-4838”, “PMID” : “15614698”, “abstract” : “BACKGROUND: Recent worldwide reports of community-onset skin abscesses, outbreaks of furunculosis, and severe pneumonia associated with methicillin-resistant Staphylococcus aureus (MRSA) carrying Panton-Valentine leukocidin (PVL) genes and the staphylococcal cassette chromosome mec (SCCmec) type IV indicate that MRSA infections are evolving into a community-related problem. The majority of cases reported to date involve skin and soft-tissue infections, with severe pneumonia representing a relatively rare phenomenon. During a 2-month period in the winter of 2003-2004, four healthy adults presented to 1 of 2 Baltimore hospitals with severe necrotizing MRSA pneumonia in the absence of typical risk factors for MRSA infection. METHODS: Patients’ MRSA isolates were characterized by strain typing with use of pulsed-field gel electrophoresis and SCCmec typing with use of a multiplex polymerase chain reaction (PCR) assay and detection of PVL genes by PCR. RESULTS: All 4 patients’ MRSA isolates carried the PVL genes and the SCCmec type IV element and belonged to the USA300 pulsed-field type. These 3 findings are among the typical characteristics of community-onset MRSA strains. In addition, 2 of our patients had concomitant influenza A diagnosed, which likely contributed to the severity of their presentation. CONCLUSIONS: To our knowledge, these patients represent the first reported North American adults with severe community-onset MRSA pneumonia caused by strains carrying the PVL genes”, “author” : { “dropping-particle” : “”, “family” : “Francis”, “given” : “J. S.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Doherty”, “given” : “M. C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lopatin”, “given” : “U.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Johnston”, “given” : “C. P.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Sinha”, “given” : “G.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ross”, “given” : “T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Cai”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hansel”, “given” : “N. N.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Perl”, “given” : “T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ticehurst”, “given” : “J. R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Carroll”, “given” : “K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Thomas”, “given” : “D. L.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Nuermberger”, “given” : “E.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Bartlett”, “given” : “J. G.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Infectious Diseases”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2005” }, “page” : “100-107”, “title” : “Severe Community-Onset Pneumonia in Healthy Adults Caused by Methicillin-Resistant Staphylococcus aureus Carrying the Panton-Valentine Leukocidin Genes”, “type” : “article-journal”, “volume” : “40” }, “uris” : “http://www.mendeley.com/documents/?uuid=8bc41e17-5875-4585-9b58-6e66cd5c3f87” } , “mendeley” : { “formattedCitation” : “(Francis et al. 2005)”, “plainTextFormattedCitation” : “(Francis et al. 2005)”, “previouslyFormattedCitation” : “(Francis et al. 2005)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Francis et al. 2005).

Moreover, CA-MRSA strains have been dignified from HA-MRSA counterparts by molecular means. Hospital acquired strains carry a relatively large staphylococcal chromosomal cassette mec (SCCmec) belonging to type I, II, or III ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/cmr.00081-09”, “ISBN” : “0893-8512”, “ISSN” : “0893-8512”, “PMID” : “20610826”, “abstract” : “Staphylococcus aureus is an important cause of skin and soft-tissue infections (SSTIs), endovascular infections, pneumonia, septic arthritis, endocarditis, osteomyelitis, foreign-body infections, and sepsis. Methicillin-resistant S. aureus (MRSA) isolates were once confined largely to hospitals, other health care environments, and patients frequenting these facilities. Since the mid-1990s, however, there has been an explosion in the number of MRSA infections reported in populations lacking risk factors for exposure to the health care system. This increase in the incidence of MRSA infection has been associated with the recognition of new MRSA clones known as community-associated MRSA (CA-MRSA). CA-MRSA strains differ from the older, health care-associated MRSA strains; they infect a different group of patients, they cause different clinical syndromes, they differ in antimicrobial susceptibility patterns, they spread rapidly among healthy people in the community, and they frequently cause infections in health care environments as well. This review details what is known about the epidemiology of CA-MRSA strains and the clinical spectrum of infectious syndromes associated with them that ranges from a commensal state to severe, overwhelming infection. It also addresses the therapy of these infections and strategies for their prevention.”, “author” : { “dropping-particle” : “”, “family” : “David”, “given” : “M Z”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Daum”, “given” : “R S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Microbiology Reviews”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2010” }, “page” : “616-687”, “title” : “Community-Associated Methicillin-Resistant Staphylococcus aureus: Epidemiology and Clinical Consequences of an Emerging Epidemic”, “type” : “article-journal”, “volume” : “23” }, “uris” : “http://www.mendeley.com/documents/?uuid=adb944f5-bc4b-4e34-a91c-98f38e1bda6e” } , “mendeley” : { “formattedCitation” : “(David and Daum 2010)”, “plainTextFormattedCitation” : “(David and Daum 2010)”, “previouslyFormattedCitation” : “(David and Daum 2010)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(David and Daum 2010). These cassettes all contain the signature of mecA gene, which is unique feature among all MRSA isolates. Hospital acquired strains are often resistant to many of non -lactam antimicrobials agents and carry the genes for the Panton-Valentine leukocidin (PVL). In other hand, Community associated strains carry smaller SCCmec elements which are commonly type IV or type V besides carrying the mecA gene and are presumably more mobile ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/cmr.00081-09”, “ISBN” : “0893-8512”, “ISSN” : “0893-8512”, “PMID” : “20610826”, “abstract” : “Staphylococcus aureus is an important cause of skin and soft-tissue infections (SSTIs), endovascular infections, pneumonia, septic arthritis, endocarditis, osteomyelitis, foreign-body infections, and sepsis. Methicillin-resistant S. aureus (MRSA) isolates were once confined largely to hospitals, other health care environments, and patients frequenting these facilities. Since the mid-1990s, however, there has been an explosion in the number of MRSA infections reported in populations lacking risk factors for exposure to the health care system. This increase in the incidence of MRSA infection has been associated with the recognition of new MRSA clones known as community-associated MRSA (CA-MRSA). CA-MRSA strains differ from the older, health care-associated MRSA strains; they infect a different group of patients, they cause different clinical syndromes, they differ in antimicrobial susceptibility patterns, they spread rapidly among healthy people in the community, and they frequently cause infections in health care environments as well. This review details what is known about the epidemiology of CA-MRSA strains and the clinical spectrum of infectious syndromes associated with them that ranges from a commensal state to severe, overwhelming infection. It also addresses the therapy of these infections and strategies for their prevention.”, “author” : { “dropping-particle” : “”, “family” : “David”, “given” : “M Z”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Daum”, “given” : “R S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Microbiology Reviews”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2010” }, “page” : “616-687”, “title” : “Community-Associated Methicillin-Resistant Staphylococcus aureus: Epidemiology and Clinical Consequences of an Emerging Epidemic”, “type” : “article-journal”, “volume” : “23” }, “uris” : “http://www.mendeley.com/documents/?uuid=adb944f5-bc4b-4e34-a91c-98f38e1bda6e” } , “mendeley” : { “formattedCitation” : “(David and Daum 2010)”, “plainTextFormattedCitation” : “(David and Daum 2010)”, “previouslyFormattedCitation” : “(David and Daum 2010)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(David and Daum 2010). These isolates are resistant to fewer non -lactam antimicrobials agents and frequently carry PVL genes in most of their strains.

Furthermore, ?-lactam antibiotics are targeting penicillin-binding proteins (PBPs) preventing peptidoglycan synthesis and this inhibition is avoided in MRSA strains through the expression of an extra PBP, named PBP2A. This enzyme is encoded by the mecA gene located within the SCCmec mobile genetic element ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1038/s41598-017-06329-2”, “ISBN” : “4159801706”, “ISSN” : “20452322”, “PMID” : “28733674”, “abstract” : “u03b2-lactam antibiotics target penicillin-binding proteins (PBPs) preventing peptidoglycan synthesis and this inhibition is circumvented in methicillin resistant Staphylococcus aureus (MRSA) strains through the expression of an additional PBP, named PBP2A. This enzyme is encoded by the mecA gene located within the Staphylococcal Chromosome Cassette mec (SCCmec) mobile genetic element, of which there are 12 types described to date. Previous investigations aimed at analysing the synergistic activity of two u03b2-lactams, oxacillin and cefoxitin, found that SCCmec type IV community-acquired MRSA strains exhibited increased susceptibility to oxacillin in the presence of cefoxitin, while hospital-acquired MRSA strains were unaffected. However, it is not clear if these differences in u03b2-lactam resistance are indeed a consequence of the presence of the different SCCmec types. To address this question, we have exchanged the SCCmec type I in COL (HA-MRSA) for the SCCmec type IV from MW2 (CA-MRSA). This exchange did not decrease the resistance of COL against oxacillin and cefoxitin, as observed in MW2, indicating that genetic features residing outside of the SCCmec element are likely to be responsible for the discrepancy in oxacillin and cefoxitin synergy against these MRSA strains.”, “author” : { “dropping-particle” : “”, “family” : “Reichmann”, “given” : “Nathalie T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pinho”, “given” : “Mariana G.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Scientific Reports”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2017” }, “title” : “Role of SCCmec type in resistance to the synergistic activity of oxacillin and cefoxitin in MRSA”, “type” : “article-journal”, “volume” : “7” }, “uris” : “http://www.mendeley.com/documents/?uuid=80c0124b-516f-4cbc-bfd1-bc8e2a746a4a” } , “mendeley” : { “formattedCitation” : “(Reichmann and Pinho 2017)”, “plainTextFormattedCitation” : “(Reichmann and Pinho 2017)”, “previouslyFormattedCitation” : “(Reichmann and Pinho 2017)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Reichmann and Pinho 2017).
Patient treatment commonly includes the utilization of ?-lactams, antibiotics that anticipate cell wall synthesis by targeting the four S. aureus PBPs capable for the transpeptidation of the peptidoglycan ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1038/s41598-017-06329-2”, “ISBN” : “4159801706”, “ISSN” : “20452322”, “PMID” : “28733674”, “abstract” : “u03b2-lactam antibiotics target penicillin-binding proteins (PBPs) preventing peptidoglycan synthesis and this inhibition is circumvented in methicillin resistant Staphylococcus aureus (MRSA) strains through the expression of an additional PBP, named PBP2A. This enzyme is encoded by the mecA gene located within the Staphylococcal Chromosome Cassette mec (SCCmec) mobile genetic element, of which there are 12 types described to date. Previous investigations aimed at analysing the synergistic activity of two u03b2-lactams, oxacillin and cefoxitin, found that SCCmec type IV community-acquired MRSA strains exhibited increased susceptibility to oxacillin in the presence of cefoxitin, while hospital-acquired MRSA strains were unaffected. However, it is not clear if these differences in u03b2-lactam resistance are indeed a consequence of the presence of the different SCCmec types. To address this question, we have exchanged the SCCmec type I in COL (HA-MRSA) for the SCCmec type IV from MW2 (CA-MRSA). This exchange did not decrease the resistance of COL against oxacillin and cefoxitin, as observed in MW2, indicating that genetic features residing outside of the SCCmec element are likely to be responsible for the discrepancy in oxacillin and cefoxitin synergy against these MRSA strains.”, “author” : { “dropping-particle” : “”, “family” : “Reichmann”, “given” : “Nathalie T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pinho”, “given” : “Mariana G.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Scientific Reports”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2017” }, “title” : “Role of SCCmec type in resistance to the synergistic activity of oxacillin and cefoxitin in MRSA”, “type” : “article-journal”, “volume” : “7” }, “uris” : “http://www.mendeley.com/documents/?uuid=80c0124b-516f-4cbc-bfd1-bc8e2a746a4a” } , “mendeley” : { “formattedCitation” : “(Reichmann and Pinho 2017)”, “plainTextFormattedCitation” : “(Reichmann and Pinho 2017)”, “previouslyFormattedCitation” : “(Reichmann and Pinho 2017)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Reichmann and Pinho 2017). Moreover, the utilization of methicillin, an early semisynthetic ?-lactam, was shortly followed by the emergence of MRSA ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1038/s41598-017-06329-2”, “ISBN” : “4159801706”, “ISSN” : “20452322”, “PMID” : “28733674”, “abstract” : “u03b2-lactam antibiotics target penicillin-binding proteins (PBPs) preventing peptidoglycan synthesis and this inhibition is circumvented in methicillin resistant Staphylococcus aureus (MRSA) strains through the expression of an additional PBP, named PBP2A. This enzyme is encoded by the mecA gene located within the Staphylococcal Chromosome Cassette mec (SCCmec) mobile genetic element, of which there are 12 types described to date. Previous investigations aimed at analysing the synergistic activity of two u03b2-lactams, oxacillin and cefoxitin, found that SCCmec type IV community-acquired MRSA strains exhibited increased susceptibility to oxacillin in the presence of cefoxitin, while hospital-acquired MRSA strains were unaffected. However, it is not clear if these differences in u03b2-lactam resistance are indeed a consequence of the presence of the different SCCmec types. To address this question, we have exchanged the SCCmec type I in COL (HA-MRSA) for the SCCmec type IV from MW2 (CA-MRSA). This exchange did not decrease the resistance of COL against oxacillin and cefoxitin, as observed in MW2, indicating that genetic features residing outside of the SCCmec element are likely to be responsible for the discrepancy in oxacillin and cefoxitin synergy against these MRSA strains.”, “author” : { “dropping-particle” : “”, “family” : “Reichmann”, “given” : “Nathalie T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pinho”, “given” : “Mariana G.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Scientific Reports”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2017” }, “title” : “Role of SCCmec type in resistance to the synergistic activity of oxacillin and cefoxitin in MRSA”, “type” : “article-journal”, “volume” : “7” }, “uris” : “http://www.mendeley.com/documents/?uuid=80c0124b-516f-4cbc-bfd1-bc8e2a746a4a” } , “mendeley” : { “formattedCitation” : “(Reichmann and Pinho 2017)”, “plainTextFormattedCitation” : “(Reichmann and Pinho 2017)”, “previouslyFormattedCitation” : “(Reichmann and Pinho 2017)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Reichmann and Pinho 2017). Currently, MRSA strains express resistance to multiple antibiotics and that is including both hospital acquired and community associated strains, which tend to be more virulent ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1038/s41598-017-06329-2”, “ISBN” : “4159801706”, “ISSN” : “20452322”, “PMID” : “28733674”, “abstract” : “u03b2-lactam antibiotics target penicillin-binding proteins (PBPs) preventing peptidoglycan synthesis and this inhibition is circumvented in methicillin resistant Staphylococcus aureus (MRSA) strains through the expression of an additional PBP, named PBP2A. This enzyme is encoded by the mecA gene located within the Staphylococcal Chromosome Cassette mec (SCCmec) mobile genetic element, of which there are 12 types described to date. Previous investigations aimed at analysing the synergistic activity of two u03b2-lactams, oxacillin and cefoxitin, found that SCCmec type IV community-acquired MRSA strains exhibited increased susceptibility to oxacillin in the presence of cefoxitin, while hospital-acquired MRSA strains were unaffected. However, it is not clear if these differences in u03b2-lactam resistance are indeed a consequence of the presence of the different SCCmec types. To address this question, we have exchanged the SCCmec type I in COL (HA-MRSA) for the SCCmec type IV from MW2 (CA-MRSA). This exchange did not decrease the resistance of COL against oxacillin and cefoxitin, as observed in MW2, indicating that genetic features residing outside of the SCCmec element are likely to be responsible for the discrepancy in oxacillin and cefoxitin synergy against these MRSA strains.”, “author” : { “dropping-particle” : “”, “family” : “Reichmann”, “given” : “Nathalie T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pinho”, “given” : “Mariana G.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Scientific Reports”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2017” }, “title” : “Role of SCCmec type in resistance to the synergistic activity of oxacillin and cefoxitin in MRSA”, “type” : “article-journal”, “volume” : “7” }, “uris” : “http://www.mendeley.com/documents/?uuid=80c0124b-516f-4cbc-bfd1-bc8e2a746a4a” } , “mendeley” : { “formattedCitation” : “(Reichmann and Pinho 2017)”, “plainTextFormattedCitation” : “(Reichmann and Pinho 2017)”, “previouslyFormattedCitation” : “(Reichmann and Pinho 2017)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Reichmann and Pinho 2017).

In 1990s, MRSA caused severe infections in children who had no history of exposure to hospitals ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/cmr.00081-09”, “ISBN” : “0893-8512”, “ISSN” : “0893-8512”, “PMID” : “20610826”, “abstract” : “Staphylococcus aureus is an important cause of skin and soft-tissue infections (SSTIs), endovascular infections, pneumonia, septic arthritis, endocarditis, osteomyelitis, foreign-body infections, and sepsis. Methicillin-resistant S. aureus (MRSA) isolates were once confined largely to hospitals, other health care environments, and patients frequenting these facilities. Since the mid-1990s, however, there has been an explosion in the number of MRSA infections reported in populations lacking risk factors for exposure to the health care system. This increase in the incidence of MRSA infection has been associated with the recognition of new MRSA clones known as community-associated MRSA (CA-MRSA). CA-MRSA strains differ from the older, health care-associated MRSA strains; they infect a different group of patients, they cause different clinical syndromes, they differ in antimicrobial susceptibility patterns, they spread rapidly among healthy people in the community, and they frequently cause infections in health care environments as well. This review details what is known about the epidemiology of CA-MRSA strains and the clinical spectrum of infectious syndromes associated with them that ranges from a commensal state to severe, overwhelming infection. It also addresses the therapy of these infections and strategies for their prevention.”, “author” : { “dropping-particle” : “”, “family” : “David”, “given” : “M Z”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Daum”, “given” : “R S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Microbiology Reviews”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2010” }, “page” : “616-687”, “title” : “Community-Associated Methicillin-Resistant Staphylococcus aureus: Epidemiology and Clinical Consequences of an Emerging Epidemic”, “type” : “article-journal”, “volume” : “23” }, “uris” : “http://www.mendeley.com/documents/?uuid=adb944f5-bc4b-4e34-a91c-98f38e1bda6e” } , “mendeley” : { “formattedCitation” : “(David and Daum 2010)”, “plainTextFormattedCitation” : “(David and Daum 2010)”, “previouslyFormattedCitation” : “(David and Daum 2010)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(David and Daum 2010). Following that incident, increasing number of CA-MRSA outbreaks continued to grow and strike not only the community but also healthcare settings in different parts of the world each year ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/978-1-62703-664-1_2”, “ISBN” : “9781627036641”, “ISSN” : “1940-6029”, “PMID” : “24085688”, “abstract” : “Over the past decade, the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the landscape of S. aureus infections around the globe. Initially recognized for its ability to cause disease in young and healthy individuals without healthcare exposures as well as for its distinct genotype and phenotype, this original description no longer fully encompasses the diversity of CA-MRSA as it continues to expand its niche. Using four case studies, we highlight a wide range of the clinical presentations and challenges of CA-MRSA. Based on these cases we further explore the globally polygenetic background of CA-MRSA with a special emphasis on generally less characterized populations.”, “author” : { “dropping-particle” : “”, “family” : “Sowash”, “given” : “Madeleine G”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Uhlemann”, “given” : “Anne-Catrin”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Methods in molecular biology (Clifton, N.J.)”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2014” }, “page” : “25-69”, “title” : “Community-associated methicillin-resistant Staphylococcus aureus case studies.”, “type” : “article-journal”, “volume” : “1085” }, “uris” : “http://www.mendeley.com/documents/?uuid=8249c17d-cae7-4e5f-9c26-5bd672156375” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1111/j.1469-0691.2012.03914.x”, “ISBN” : “1469-0691 (Electronic) 1198-743X (Linking)”, “ISSN” : “14690691”, “PMID” : “22712729”, “abstract” : “Clin Microbiol Infect Abstract The economic impact of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) remains unclear. We developed an economic simulation model to quantify the costs associated with CA-MRSA infection from the societal and third-party payer perspectives. A single CA-MRSA case costs third-party payers 2277u20133200 and society 7070u201320 489, depending on patient age. In the United States (US), CA-MRSA imposes an annual burden of 478 million to 2.2 billion on third-party payers and 1.4u201313.8 billion on society, depending on the CA-MRSA definitions and incidences. The US jail system and Army may be experiencing annual total costs of 7u201311 million (6u201310 million direct medical costs) and 15u201336 million (14u201332 million direct costs), respectively. Hospitalization rates and mortality are important cost drivers. CA-MRSA confers a substantial economic burden on third-party payers and society, with CA-MRSA-attributable productivity losses being major contributors to the total societal economic burden. Although decreasing transmission and infection incidence would decrease costs, even if transmission were to continue at present levels, early identification and appropriate treatment of CA-MRSA infections before they progress could save considerable costs.”, “author” : { “dropping-particle” : “”, “family” : “Lee”, “given” : “B. Y.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Singh”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “David”, “given” : “M. Z.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Bartsch”, “given” : “S. M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Slayton”, “given” : “R. B.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Huang”, “given” : “S. S.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zimmer”, “given” : “S. M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Potter”, “given” : “M. A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Macal”, “given” : “C. M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lauderdale”, “given” : “D. S.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Miller”, “given” : “L. G.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Daum”, “given” : “R. S.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Microbiology and Infection”, “id” : “ITEM-2”, “issue” : “6”, “issued” : { “date-parts” : “2013” }, “page” : “528-536”, “title” : “The economic burden of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)”, “type” : “article-journal”, “volume” : “19” }, “uris” : “http://www.mendeley.com/documents/?uuid=f7930374-aaa6-4f52-9ca2-329095827ca2” } , “mendeley” : { “formattedCitation” : “(Lee et al. 2013; Sowash and Uhlemann 2014)”, “plainTextFormattedCitation” : “(Lee et al. 2013; Sowash and Uhlemann 2014)”, “previouslyFormattedCitation” : “(Lee et al. 2013; Sowash and Uhlemann 2014)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Lee et al. 2013; Sowash and Uhlemann 2014).

Different lineages of CA-MRSA are circulating epidemiological regions around the world. In general, five clonal lineages are known to cause most of the global CA-MRSA outbreaks ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/cmr.00081-09”, “ISBN” : “0893-8512”, “ISSN” : “0893-8512”, “PMID” : “20610826”, “abstract” : “Staphylococcus aureus is an important cause of skin and soft-tissue infections (SSTIs), endovascular infections, pneumonia, septic arthritis, endocarditis, osteomyelitis, foreign-body infections, and sepsis. Methicillin-resistant S. aureus (MRSA) isolates were once confined largely to hospitals, other health care environments, and patients frequenting these facilities. Since the mid-1990s, however, there has been an explosion in the number of MRSA infections reported in populations lacking risk factors for exposure to the health care system. This increase in the incidence of MRSA infection has been associated with the recognition of new MRSA clones known as community-associated MRSA (CA-MRSA). CA-MRSA strains differ from the older, health care-associated MRSA strains; they infect a different group of patients, they cause different clinical syndromes, they differ in antimicrobial susceptibility patterns, they spread rapidly among healthy people in the community, and they frequently cause infections in health care environments as well. This review details what is known about the epidemiology of CA-MRSA strains and the clinical spectrum of infectious syndromes associated with them that ranges from a commensal state to severe, overwhelming infection. It also addresses the therapy of these infections and strategies for their prevention.”, “author” : { “dropping-particle” : “”, “family” : “David”, “given” : “M Z”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Daum”, “given” : “R S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Microbiology Reviews”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2010” }, “page” : “616-687”, “title” : “Community-Associated Methicillin-Resistant Staphylococcus aureus: Epidemiology and Clinical Consequences of an Emerging Epidemic”, “type” : “article-journal”, “volume” : “23” }, “uris” : “http://www.mendeley.com/documents/?uuid=adb944f5-bc4b-4e34-a91c-98f38e1bda6e” } , “mendeley” : { “formattedCitation” : “(David and Daum 2010)”, “plainTextFormattedCitation” : “(David and Daum 2010)”, “previouslyFormattedCitation” : “(David and Daum 2010)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(David and Daum 2010), Sequence Type 1 (ST1) which is known to circulate north America, Europe and Australia; 2) ST59 that is dominating China, Taiwan and Vietnam; 3) ST30 which has control over Japan, United States and Malaysia in addition to some parts of the Middle East; 4) ST8/USA300 which is mainly restricted to north America and Europe; and 5) ST80 that dominates northern Africa, Europe and Kuwait ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S1473-3099(13)70136-1”, “ISSN” : “14733099”, “PMID” : “23827369”, “abstract” : “In Asia, most reports on the epidemiology of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) are from developed countries, with few data from resource-limited countries, not because of low actual prevalence, but probably because of scarce diagnostic facilities. The rate of MRSA in all community-associated S aureus infections in Asian countries ranges from 2??5% to 39%. Unlike the predominance of USA300-sequence type (ST) 8 staphylococcal cassette chromosome mec (SCC. mec) type IV in the USA, the molecular epidemiology of CA-MRSA in Asia is characterised by clonal heterogeneity, similar to that in Europe. The emergence of CA-MRSA is a threat in both community and hospital settings because such strains are now more prevalent than are health-care-associated MRSA (HA-MRSA) strains. Many epidemic clones are in circulation in Asia and with scarce data available, concern has arisen that CA-MRSA could have devastating results if it becomes epidemic in resource-poor regions. The epidemiology of CA-MRSA in Asia is closely linked with the health of both developing and developed countries. The present situation of CA-MRSA in Asia is important not only for local public health, but also to provide a better understanding of the successful epidemic clones of this global pathogen. ?? 2013 Elsevier Ltd.”, “author” : { “dropping-particle” : “”, “family” : “Chuang”, “given” : “Yu Yu”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Huang”, “given” : “Yhu Chering”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Lancet Infectious Diseases”, “id” : “ITEM-1”, “issue” : “8”, “issued” : { “date-parts” : “2013” }, “page” : “698-708”, “title” : “Molecular epidemiology of community-associated meticillin-resistant Staphylococcus aureus in Asia”, “type” : “article”, “volume” : “13” }, “uris” : “http://www.mendeley.com/documents/?uuid=48893d7a-3f45-4db2-8453-b368fe4f2bc9” } , “mendeley” : { “formattedCitation” : “(Chuang and Huang 2013)”, “plainTextFormattedCitation” : “(Chuang and Huang 2013)”, “previouslyFormattedCitation” : “(Chuang and Huang 2013)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Chuang and Huang 2013) However, data on the circulating CA-MRSA lineages in Saudi Arabia is severely lacking.
Several molecular techniques are available for CA-MRSA genotyping studies. For instance, whole genome sequencing (WGS) is considered one of the most effective technology to reveal the genetic characteristics of CA-MRSA including information about their virulence and epidemiological spread in an outbreak ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/978-1-62703-664-1_2”, “ISBN” : “9781627036641”, “ISSN” : “1940-6029”, “PMID” : “24085688”, “abstract” : “Over the past decade, the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the landscape of S. aureus infections around the globe. Initially recognized for its ability to cause disease in young and healthy individuals without healthcare exposures as well as for its distinct genotype and phenotype, this original description no longer fully encompasses the diversity of CA-MRSA as it continues to expand its niche. Using four case studies, we highlight a wide range of the clinical presentations and challenges of CA-MRSA. Based on these cases we further explore the globally polygenetic background of CA-MRSA with a special emphasis on generally less characterized populations.”, “author” : { “dropping-particle” : “”, “family” : “Sowash”, “given” : “Madeleine G”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Uhlemann”, “given” : “Anne-Catrin”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Methods in molecular biology (Clifton, N.J.)”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2014” }, “page” : “25-69”, “title” : “Community-associated methicillin-resistant Staphylococcus aureus case studies.”, “type” : “article-journal”, “volume” : “1085” }, “uris” : “http://www.mendeley.com/documents/?uuid=8249c17d-cae7-4e5f-9c26-5bd672156375” } , “mendeley” : { “formattedCitation” : “(Sowash and Uhlemann 2014)”, “plainTextFormattedCitation” : “(Sowash and Uhlemann 2014)”, “previouslyFormattedCitation” : “(Sowash and Uhlemann 2014)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Sowash and Uhlemann 2014). However, the major drawbacks of using WGS are the high cost and the need for an automated data interpretation system. On the other hand, pulse field gel electrophoresis (PFGE) is considered the gold standard for MRSA typing, and multilocus sequence typing (MLST) is one of the most commonly used methods for MRSA typing. Nonetheless, these techniques require special equipment and high level of experience to interpret the resultADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/978-1-62703-664-1_2”, “ISBN” : “9781627036641”, “ISSN” : “1940-6029”, “PMID” : “24085688”, “abstract” : “Over the past decade, the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the landscape of S. aureus infections around the globe. Initially recognized for its ability to cause disease in young and healthy individuals without healthcare exposures as well as for its distinct genotype and phenotype, this original description no longer fully encompasses the diversity of CA-MRSA as it continues to expand its niche. Using four case studies, we highlight a wide range of the clinical presentations and challenges of CA-MRSA. Based on these cases we further explore the globally polygenetic background of CA-MRSA with a special emphasis on generally less characterized populations.”, “author” : { “dropping-particle” : “”, “family” : “Sowash”, “given” : “Madeleine G”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Uhlemann”, “given” : “Anne-Catrin”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Methods in molecular biology (Clifton, N.J.)”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2014” }, “page” : “25-69”, “title” : “Community-associated methicillin-resistant Staphylococcus aureus case studies.”, “type” : “article-journal”, “volume” : “1085” }, “uris” : “http://www.mendeley.com/documents/?uuid=8249c17d-cae7-4e5f-9c26-5bd672156375” } , “mendeley” : { “formattedCitation” : “(Sowash and Uhlemann 2014)”, “plainTextFormattedCitation” : “(Sowash and Uhlemann 2014)”, “previouslyFormattedCitation” : “(Sowash and Uhlemann 2014)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Sowash and Uhlemann 2014). Recently, Al-Zahrani et.al. developed a simple SmaI restriction site-based multiplex PCR (SmaI-multiplex PCR) typing technique (SMT) to identify the single-nucleotide polymorphism (SNP) variations in and around SmaI-restriction sites ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/JCM.00857-11”, “ISBN” : “0095-1137”, “ISSN” : “00951137”, “PMID” : “21940477”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen, and morbidity and mortality rates associated with this pathogen have increased markedly in recent years. MRSA strains are generally resistant to several classes of antibiotics and are therefore difficult and costly to treat. A major issue is to identify the sources of MRSA infections and to monitor their epidemic spread. In this study, we report the development of a typing technique for S. aureus, based on single-nucleotide polymorphism (SNP) variations in and around SmaI-restriction sites (CCCGGG). An assessment of the SmaI restriction site-based multiplex PCR (SmaI-multiplex PCR) typing (SMT) with respect to pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) revealed a high level of concordance in the clustering of the test strains. The SmaI-multiplex PCR was found to be more discriminatory than MLST/staphylococcal cassette chromosome mec (SCCmec) typing but less discriminatory than PFGE. SMT can provide real-time information for the investigation of ongoing S. aureus hospital outbreaks. SMT meets the criteria of a practical typing method: it is simple, reproducible, and highly discriminatory and does not require expensive equipment or specialist expertise. Consequently, SmaI-multiplex PCR has the potential to be used in routine clinical microbiology laboratories.”, “author” : { “dropping-particle” : “”, “family” : “Al-Zahrani”, “given” : “Ibrahim A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hamson”, “given” : “Clare”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Edge”, “given” : “David”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Collins”, “given” : “Jennifer”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Perry”, “given” : “John D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Raza”, “given” : “Muhammad”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gould”, “given” : “Kate”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Harwood”, “given” : “Colin R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Clinical Microbiology”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2011” }, “title” : “SmaI restriction site-based multiplex PCR for typing of hospital- and community-acquired Staphylococcus aureus”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=3d3a7915-400b-311c-8ee5-2c745636d993” } , “mendeley” : { “formattedCitation” : “(Al-Zahrani et al. 2011)”, “plainTextFormattedCitation” : “(Al-Zahrani et al. 2011)”, “previouslyFormattedCitation” : “(Al-Zahrani et al. 2011)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Al-Zahrani et al. 2011). SMT proved to be highly reproducible with comparable result to MRSA pulse field gel electrophoresis typing but with significantly lower cost ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/JCM.00857-11”, “ISBN” : “0095-1137”, “ISSN” : “00951137”, “PMID” : “21940477”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen, and morbidity and mortality rates associated with this pathogen have increased markedly in recent years. MRSA strains are generally resistant to several classes of antibiotics and are therefore difficult and costly to treat. A major issue is to identify the sources of MRSA infections and to monitor their epidemic spread. In this study, we report the development of a typing technique for S. aureus, based on single-nucleotide polymorphism (SNP) variations in and around SmaI-restriction sites (CCCGGG). An assessment of the SmaI restriction site-based multiplex PCR (SmaI-multiplex PCR) typing (SMT) with respect to pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) revealed a high level of concordance in the clustering of the test strains. The SmaI-multiplex PCR was found to be more discriminatory than MLST/staphylococcal cassette chromosome mec (SCCmec) typing but less discriminatory than PFGE. SMT can provide real-time information for the investigation of ongoing S. aureus hospital outbreaks. SMT meets the criteria of a practical typing method: it is simple, reproducible, and highly discriminatory and does not require expensive equipment or specialist expertise. Consequently, SmaI-multiplex PCR has the potential to be used in routine clinical microbiology laboratories.”, “author” : { “dropping-particle” : “”, “family” : “Al-Zahrani”, “given” : “Ibrahim A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hamson”, “given” : “Clare”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Edge”, “given” : “David”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Collins”, “given” : “Jennifer”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Perry”, “given” : “John D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Raza”, “given” : “Muhammad”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gould”, “given” : “Kate”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Harwood”, “given” : “Colin R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Clinical Microbiology”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2011” }, “title” : “SmaI restriction site-based multiplex PCR for typing of hospital- and community-acquired Staphylococcus aureus”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=3d3a7915-400b-311c-8ee5-2c745636d993” } , “mendeley” : { “formattedCitation” : “(Al-Zahrani et al. 2011)”, “plainTextFormattedCitation” : “(Al-Zahrani et al. 2011)”, “previouslyFormattedCitation” : “(Al-Zahrani et al. 2011)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Al-Zahrani et al. 2011). Thus, the SMT technique can be utilized to genotype large number of isolated CA-MRSA strains with relatively low cost.

The main purpose of this research to investigate the prevalence of Staphylococcus aureus and CA-MRSA in nasal carriage of athletes group. Moreover, understand the global molecular epidemiology of CA-MRSA and in particular MRSA infections. All that due to the of nature of the pathogen to emerge and manipulate with its genomic structure on base of various factor.
Staphylococcus aureus general description:From the Greek staphyle (bunch of grapes) and kokkos (berry), Staphylococcus aureus have its name. it classified as gram positive bacteria under the genus of Staphylococcus and species of Staphylococcus aureus, which present under the microscopic examination as purple grape cluster arrangement’s CITATION cdc16 l 1033 (Centers for Disease Control and Prevention, 2011) . Notwithstanding the fact that S. aureus is a normal component of the microbiota of the nasal passages, skin and mucous membranes of humans and animals, it is the reason of several important diseases ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/jac/dki372”, “ISBN” : “0305-7453”, “ISSN” : “0305-7453”, “PMID” : “16293678”, “abstract” : “These evidence-based guidelines have been produced after a literature review of the laboratory diagnosis and susceptibility testing of methicillin-resistant Staphylococcus aureus (MRSA). We have considered the detection of MRSA in screening samples and the detection of reduced susceptibility to glycopeptides in S. aureus. Recommendations are given for the identification of S. aureus and for suitable methods of susceptibility testing and screening for MRSA and for S. aureus with reduced susceptibility to glycopeptides. These guidelines indicate what tests should be used but not when the tests are applicable, as aspects of this are dealt with in guidelines on control of MRSA. There are currently several developments in screening media and molecular methods. It is likely that some of our recommendations will require modification as the new methods become available.”, “author” : { “dropping-particle” : “”, “family” : “Brown”, “given” : “Derek F J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Edwards”, “given” : “David I”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hawkey”, “given” : “Peter M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Morrison”, “given” : “Donald”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ridgway”, “given” : “Geoffrey L”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Towner”, “given” : “Kevin J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Wren”, “given” : “Michael W D”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Journal of antimicrobial chemotherapy”, “id” : “ITEM-1”, “issue” : “6”, “issued” : { “date-parts” : “2005” }, “page” : “1000-18”, “title” : “Guidelines for the laboratory diagnosis and susceptibility testing of methicillin-resistant Staphylococcus aureus (MRSA).”, “type” : “article-journal”, “volume” : “56” }, “uris” : “http://www.mendeley.com/documents/?uuid=6eae11a8-fff8-4d16-b7be-d0f923e8fcaa” } , “mendeley” : { “formattedCitation” : “(Brown et al. 2005)”, “plainTextFormattedCitation” : “(Brown et al. 2005)”, “previouslyFormattedCitation” : “(Brown et al. 2005)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Brown et al. 2005). More than thirty percent of people carry it in their nasal cavity without any health care complicationCITATION cdc16 l 1033 (Centers for Disease Control and Prevention, 2011).

History of S. aureus:Pasteur and Koch were the first who discover and culture Staphylococcus but without carrying out any detailed studies for this explorer. While in 1880, Scottish surgeon Sir Alexander Ogston first described staphylococci in pus sample from a surgical abscess in a knee joint where the masses noticed as bunches of grapes. Moreover in 1884, German physician Friedrich Julius Rosenbach differentiated the bacteria by adding its species name aureus (=gold) based on its color. Rosenbach also reported that S. aureus caused some wound infections whereas S. epidermidis lived on the skin as a colonizer (Cookson et al., 2003).
S. aureus Economical burden:
S. aureus infection has been reported in 14 million outpatients through the United State of America. In other hand, (MRSA) infection consider as the major cause of death at the USA. Previously MRSA was linked to Nosocomial infection or hospital acquired infection (HAI), recently, the presence of CA-MRSA with high prevalence became the major cause of infection in skin and soft tissues and it is invading both community and healthcare facilities ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.4085/1062-6050-49.3.96”, “ISSN” : “10626050”, “PMID” : “25710853”, “abstract” : “CONTEXT:: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a leading cause of skin and soft tissue infection in the nonhospitalized community. Care of the athletes in athletic training rooms is specifically designed with equipment tailored to the health care needs of the athletes, yet recent studies indicate that CA-MRSA is still prevalent in athletic facilities and that cleaning methods may not be optimal. OBJECTIVE:: To investigate the prevalence of Staphylococcus aureus and CA-MRSA in and around whirlpools in the athletic training room. DESIGN:: Cross-sectional study. SETTING:: National Collegiate Athletic Association Division I university. PATIENTS OR OTHER PARTICIPANTS:: Student-athletes (n = 109) consisting of 46 men (42%) and 63 women (58%) representing 6 sports. MAIN OUTCOME MEASURE(S):: Presence of MRSA and Staphylococcus aureus in and around the whirlpool structures relative to sport and number of athletes using the whirlpools. RESULTS:: We identified Staphylococcus aureus in 22% (n = 52/240) of the samples and MRSA in 0.8% (n = 2/240). A statistically significant difference existed between the number of athletes using the whirlpool and the presence of Staphylococcus aureus in and around the whirlpools (F(2,238) = 2.445, P = .007). However, Staphylococcus aureus was identified regardless of whether multiple athletes used a whirlpool or no athletes used a whirlpool. We did not identify a relationship between the number of athletes who used a whirlpool and Staphylococcus aureus or MRSA density (P = .134). CONCLUSIONS:: Staphylococcus aureus and MRSA were identified in and around the whirlpools. Transmission of the bacteria can be reduced by following the cleaning and disinfecting protocols recommended by the Centers for Disease Control and Prevention. Athletic trainers should use disinfectants registered by the Environmental Protection Agency to sanitize all whirlpools between uses. “, “author” : { “dropping-particle” : “”, “family” : “Kahanov”, “given” : “Leamor”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kim”, “given” : “Young Kyun”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Eberman”, “given” : “Lindsey”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dannelly”, “given” : “Kathleen”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kaur”, “given” : “Haninder”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ramalinga”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Athletic Training”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2015” }, “page” : “432-437”, “title” : “Staphylococcus aureus and Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) in and around therapeutic whirlpools in college athletic training rooms”, “type” : “article-journal”, “volume” : “50” }, “uris” : “http://www.mendeley.com/documents/?uuid=e52162d4-617c-43d3-9e66-5b9847bef709” } , “mendeley” : { “formattedCitation” : “(Kahanov et al. 2015)”, “plainTextFormattedCitation” : “(Kahanov et al. 2015)”, “previouslyFormattedCitation” : “(Kahanov et al. 2015)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Kahanov et al. 2015).

MRSA is considered as a major cause of death in the United States ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.4085/1062-6050-49.3.96”, “ISSN” : “10626050”, “PMID” : “25710853”, “abstract” : “CONTEXT:: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a leading cause of skin and soft tissue infection in the nonhospitalized community. Care of the athletes in athletic training rooms is specifically designed with equipment tailored to the health care needs of the athletes, yet recent studies indicate that CA-MRSA is still prevalent in athletic facilities and that cleaning methods may not be optimal. OBJECTIVE:: To investigate the prevalence of Staphylococcus aureus and CA-MRSA in and around whirlpools in the athletic training room. DESIGN:: Cross-sectional study. SETTING:: National Collegiate Athletic Association Division I university. PATIENTS OR OTHER PARTICIPANTS:: Student-athletes (n = 109) consisting of 46 men (42%) and 63 women (58%) representing 6 sports. MAIN OUTCOME MEASURE(S):: Presence of MRSA and Staphylococcus aureus in and around the whirlpool structures relative to sport and number of athletes using the whirlpools. RESULTS:: We identified Staphylococcus aureus in 22% (n = 52/240) of the samples and MRSA in 0.8% (n = 2/240). A statistically significant difference existed between the number of athletes using the whirlpool and the presence of Staphylococcus aureus in and around the whirlpools (F(2,238) = 2.445, P = .007). However, Staphylococcus aureus was identified regardless of whether multiple athletes used a whirlpool or no athletes used a whirlpool. We did not identify a relationship between the number of athletes who used a whirlpool and Staphylococcus aureus or MRSA density (P = .134). CONCLUSIONS:: Staphylococcus aureus and MRSA were identified in and around the whirlpools. Transmission of the bacteria can be reduced by following the cleaning and disinfecting protocols recommended by the Centers for Disease Control and Prevention. Athletic trainers should use disinfectants registered by the Environmental Protection Agency to sanitize all whirlpools between uses. “, “author” : { “dropping-particle” : “”, “family” : “Kahanov”, “given” : “Leamor”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kim”, “given” : “Young Kyun”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Eberman”, “given” : “Lindsey”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dannelly”, “given” : “Kathleen”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kaur”, “given” : “Haninder”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ramalinga”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Athletic Training”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2015” }, “page” : “432-437”, “title” : “Staphylococcus aureus and Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) in and around therapeutic whirlpools in college athletic training rooms”, “type” : “article-journal”, “volume” : “50” }, “uris” : “http://www.mendeley.com/documents/?uuid=e52162d4-617c-43d3-9e66-5b9847bef709” } , “mendeley” : { “formattedCitation” : “(Kahanov et al. 2015)”, “plainTextFormattedCitation” : “(Kahanov et al. 2015)”, “previouslyFormattedCitation” : “(Kahanov et al. 2015)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Kahanov et al. 2015) with about 90,000 annual reported invasive cases and 20,000 annual deaths (Centers for Disease Control and Prevention, 2011). It is estimated that MRSA infections cost the US hospitals from 1.5 to 4.2 billion dollars annually ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.ijantimicag.2006.09.001”, “ISBN” : “0924-8579 (Print) 0924-8579 (Linking)”, “ISSN” : “09248579”, “PMID” : “17045462”, “abstract” : “For most countries badly affected by methicillin-resistant Staphylococcus aureus (MRSA) there have been many years of debate about its relative virulence compared with methicillin-susceptible S. aureus (MSSA) and whether it could be controlled. Now that it is endemic in the majority of hospitals around the world, it is clear that it is at least as virulent as MSSA and is an additional burden of healthcare-acquired infection. There is increasing evidence that, despite this endemicity, control efforts can be successful, although they are often perceived as expensive. In reality, there is a large body of consistent evidence that control is highly cost effective, particularly in the context of the huge societal costs of MRSA and the future ever-greater threats that it poses. ?? 2006 Elsevier B.V. and the International Society of Chemotherapy.”, “author” : { “dropping-particle” : “”, “family” : “Gould”, “given” : “I. M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “International Journal of Antimicrobial Agents”, “id” : “ITEM-1”, “issue” : “5”, “issued” : { “date-parts” : “2006” }, “page” : “379-384”, “title” : “Costs of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) and its control”, “type” : “article”, “volume” : “28” }, “uris” : “http://www.mendeley.com/documents/?uuid=363fd8ec-3836-431d-9d5e-4be9783347e3” } , “mendeley” : { “formattedCitation” : “(I. M. Gould 2006)”, “plainTextFormattedCitation” : “(I. M. Gould 2006)”, “previouslyFormattedCitation” : “(I. M. Gould 2006)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(I. M. Gould 2006). Therefore, it is clear that MRSA infections have a significant impact on population health and substantial economic burden.

S. aureus genome:The genome of S. aureus has been substantially studied and currently 18 Staphylococcal genomes (Table.1.1) have been effectively sequenced (nine are MRSA (four of which are vancomycin-intermediate resistant S. aureus (VISA)) and 9 are MSSA) and a in addition 28 genomes are presently being sequenced (some of them within the finishing stage). This has provided an exceptional glimpse into this so-known as “super genome” and has prompt an extensive gain in our understanding of the structure and functioning of S. aureus.

Staphylococcal genome is a closed circular molecule of double-stranded (ds) DNA of among 2.7 – 3.0 Mbp in length, encoding between 2509 to 2892 open reading frames (ORFs). it is composed of domain names called the middle genome and the accessory genome. The central genome is inherited from the ancestors and is extraordinarily conserved in all staphylococcal species. ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “ISSN” : “1044-7946”, “PMID” : “25942745”, “abstract” : “Staphylococcus aureus continues to be a serious health problem worldwide due to its intrinsic nature of virulence, ability to cause a wide array of infection, and its capacity to develop resistance to a number of antibiotics. The S aureus genome has continually evolved through both mutation and acquisition of exogenous genes, leading to the emergence of antibiotic-resistant strains with the ability for clonaldissemination across nations and continents. Methicillin-resistant S aureus (MRSA) is one of the most commonly identified antibioticresistant pathogens in the hospital and community settings with substantial mortality and morbidity. This review examines the accessory genome of 8 sequenced S aureus strains regarding the variety of virulence factors and mechanisms of antibiotic resistance. The remarkable nature of this organism to acquire and disseminate an array of mobile genetic elements (MBEs) through horizontal gene transfer illustrates the mechanisms for evolution and its fitness level in the face of constant environmental challenges. 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The middle incorporates approximately 75 % of S. aureus chromosome and it is surprisingly conserved among lines ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.tim.2004.06.004”, “ISBN” : “0966-842X (Print)\n0966-842X (Linking)”, “ISSN” : “0966842X”, “PMID” : “15276614”, “abstract” : “Staphylococcus aureus is a common cause of infection in both hospitals and the community, and it is becoming increasingly virulent and resistant to antibiotics. The recent sequencing of seven strains of S. aureus provides unprecedented information about its genome diversity. Subtle differences in core (stable) regions of the genome have been exploited by multi-locus sequence typing (MLST) to understand S. aureus population structure. Dramatic differences in the carriage and spread of accessory genes, including those involved in virulence and resistance, contribute to the emergence of new strains with healthcare implications. 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It includes all of the housekeeping genes which might be required for crucial cell functions, together with DNA replication, proteins synthesis and center metabolism and so forth. The genome includes an extensive diversity of genes encode capabilities that contribute to virulence, inclusive of pollutants, exoenzymes and pill biosynthetic cluster. The battery of virulence genes is fairly pressure variable ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “ISSN” : “1044-7946”, “PMID” : “25942745”, “abstract” : “Staphylococcus aureus continues to be a serious health problem worldwide due to its intrinsic nature of virulence, ability to cause a wide array of infection, and its capacity to develop resistance to a number of antibiotics. The S aureus genome has continually evolved through both mutation and acquisition of exogenous genes, leading to the emergence of antibiotic-resistant strains with the ability for clonaldissemination across nations and continents. Methicillin-resistant S aureus (MRSA) is one of the most commonly identified antibioticresistant pathogens in the hospital and community settings with substantial mortality and morbidity. This review examines the accessory genome of 8 sequenced S aureus strains regarding the variety of virulence factors and mechanisms of antibiotic resistance. The remarkable nature of this organism to acquire and disseminate an array of mobile genetic elements (MBEs) through horizontal gene transfer illustrates the mechanisms for evolution and its fitness level in the face of constant environmental challenges. The relative ease of transfer of genetic materials, especially antibiotic-resistant genes, across staphylococcal species indicates that there is a potential pandemic problem in the hospital and community environment.”, “author” : { “dropping-particle” : “”, “family” : “Shittu”, “given” : “a O”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Udo”, “given” : “E E”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lin”, “given” : “J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Wounds: A Compendium of Clinical Research & Practice”, “id” : “ITEM-1”, “issue” : “9”, “issued” : { “date-parts” : “2007” }, “page” : “237-244”, “title” : “Insights on virulence and antibiotic resistance: a review of the accessory genome of Staphylococcus aureus.”, “type” : “article-journal”, “volume” : “19” }, “uris” : “http://www.mendeley.com/documents/?uuid=a7cf0ca9-9d88-450b-bd7d-133501c1df13” } , “mendeley” : { “formattedCitation” : “(Shittu, Udo, and Lin 2007)”, “plainTextFormattedCitation” : “(Shittu, Udo, and Lin 2007)”, “previouslyFormattedCitation” : “(Shittu, Udo, and Lin 2007)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Shittu, Udo, and Lin 2007).

The second domain area, comprising of ~25% of the staphylococcal genome, is the accent genome. The accent genome usually consists of mobile genetics elements (MGEs) that encode variety of non-important components required for growth and survival. those factors include pathogenicity islands, bacteriophages, chromosomal cassettes, genomic islands, plasmids and transposons. a lot of these factors encode virulence and antibiotic-resistance determinants which are transferred horizontally between strains of medical significance ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.tim.2004.06.004”, “ISBN” : “0966-842X (Print)\n0966-842X (Linking)”, “ISSN” : “0966842X”, “PMID” : “15276614”, “abstract” : “Staphylococcus aureus is a common cause of infection in both hospitals and the community, and it is becoming increasingly virulent and resistant to antibiotics. The recent sequencing of seven strains of S. aureus provides unprecedented information about its genome diversity. Subtle differences in core (stable) regions of the genome have been exploited by multi-locus sequence typing (MLST) to understand S. aureus population structure. Dramatic differences in the carriage and spread of accessory genes, including those involved in virulence and resistance, contribute to the emergence of new strains with healthcare implications. Understanding the differences between S. aureus genomes and the controls that govern these changes is helping to improve our knowledge of S. aureus pathogenicity and to predict the evolution of super-superbugs.”, “author” : { “dropping-particle” : “”, “family” : “Lindsay”, “given” : “Jodi A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Holden”, “given” : “Matthew T G”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Trends in Microbiology”, “id” : “ITEM-1”, “issue” : “8”, “issued” : { “date-parts” : “2004” }, “page” : “378-385”, “title” : “Staphylococcus aureus: Superbug, super genome?”, “type” : “article”, “volume” : “12” }, “uris” : “http://www.mendeley.com/documents/?uuid=7b7014b0-166d-46db-85e4-ec64c47edbbb” }, { “id” : “ITEM-2”, “itemData” : { “ISSN” : “1044-7946”, “PMID” : “25942745”, “abstract” : “Staphylococcus aureus continues to be a serious health problem worldwide due to its intrinsic nature of virulence, ability to cause a wide array of infection, and its capacity to develop resistance to a number of antibiotics. The S aureus genome has continually evolved through both mutation and acquisition of exogenous genes, leading to the emergence of antibiotic-resistant strains with the ability for clonaldissemination across nations and continents. Methicillin-resistant S aureus (MRSA) is one of the most commonly identified antibioticresistant pathogens in the hospital and community settings with substantial mortality and morbidity. This review examines the accessory genome of 8 sequenced S aureus strains regarding the variety of virulence factors and mechanisms of antibiotic resistance. The remarkable nature of this organism to acquire and disseminate an array of mobile genetic elements (MBEs) through horizontal gene transfer illustrates the mechanisms for evolution and its fitness level in the face of constant environmental challenges. The relative ease of transfer of genetic materials, especially antibiotic-resistant genes, across staphylococcal species indicates that there is a potential pandemic problem in the hospital and community environment.”, “author” : { “dropping-particle” : “”, “family” : “Shittu”, “given” : “a O”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Udo”, “given” : “E E”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lin”, “given” : “J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Wounds: A Compendium of Clinical Research & Practice”, “id” : “ITEM-2”, “issue” : “9”, “issued” : { “date-parts” : “2007” }, “page” : “237-244”, “title” : “Insights on virulence and antibiotic resistance: a review of the accessory genome of Staphylococcus aureus.”, “type” : “article-journal”, “volume” : “19” }, “uris” : “http://www.mendeley.com/documents/?uuid=a7cf0ca9-9d88-450b-bd7d-133501c1df13” } , “mendeley” : { “formattedCitation” : “(Lindsay and Holden 2004; Shittu, Udo, and Lin 2007)”, “plainTextFormattedCitation” : “(Lindsay and Holden 2004; Shittu, Udo, and Lin 2007)”, “previouslyFormattedCitation” : “(Lindsay and Holden 2004; Shittu, Udo, and Lin 2007)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Lindsay and Holden 2004; Shittu, Udo, and Lin 2007).

There is initial evidence to suggest that a number of MGEs move among isolates at a high frequency while others move if simplest rarely. despite the fact that, the transfer mechanisms aren’t fully understood, valuable information has been acquired about how S. aureus causes infection from the characterization and identification of MGEs. several researches advise that undoubting virulence and antibiotic-resistance determinants are related to unique strains and types of infection ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.tim.2004.06.004”, “ISBN” : “0966-842X (Print)\n0966-842X (Linking)”, “ISSN” : “0966842X”, “PMID” : “15276614”, “abstract” : “Staphylococcus aureus is a common cause of infection in both hospitals and the community, and it is becoming increasingly virulent and resistant to antibiotics. The recent sequencing of seven strains of S. aureus provides unprecedented information about its genome diversity. Subtle differences in core (stable) regions of the genome have been exploited by multi-locus sequence typing (MLST) to understand S. aureus population structure. Dramatic differences in the carriage and spread of accessory genes, including those involved in virulence and resistance, contribute to the emergence of new strains with healthcare implications. Understanding the differences between S. aureus genomes and the controls that govern these changes is helping to improve our knowledge of S. aureus pathogenicity and to predict the evolution of super-superbugs.”, “author” : { “dropping-particle” : “”, “family” : “Lindsay”, “given” : “Jodi A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Holden”, “given” : “Matthew T G”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Trends in Microbiology”, “id” : “ITEM-1”, “issue” : “8”, “issued” : { “date-parts” : “2004” }, “page” : “378-385”, “title” : “Staphylococcus aureus: Superbug, super genome?”, “type” : “article”, “volume” : “12” }, “uris” : “http://www.mendeley.com/documents/?uuid=7b7014b0-166d-46db-85e4-ec64c47edbbb” } , “mendeley” : { “formattedCitation” : “(Lindsay and Holden 2004)”, “plainTextFormattedCitation” : “(Lindsay and Holden 2004)”, “previouslyFormattedCitation” : “(Lindsay and Holden 2004)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Lindsay and Holden 2004).

Pathogenesis and virulence factors:Due to the discrete phenotype and genotype it causes infections in young and healthy people without any exposure to the healthcare environments. S. aureus recall as important human pathogen and colonizer in approximately 30–50 % of mankind on mucosal surfaces and skin. However, under the right conditions this superbug is able to cause a wide range of infections ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1086/520289”, “ISBN” : “1058-4838”, “ISSN” : “1058-4838”, “PMID” : “9597249”, “abstract” : “Staphylococcus aureus is a virulent pathogen that is currently the most common cause of infections in hospitalized patients. S. aureus infection can involve any organ system. The success of S. aureus as a pathogen and its ability to cause such a wide range of infections are the result of its extensive virulence factors. The increase in the resistance of this virulent pathogen to antibacterial agents, coupled with its increasing prevalence as a nosocomial pathogen, is of major concern. The core resistance phenotype that seems to be most associated with the persistence of S. aureus in the hospital is methicillin resistance. Methicillin resistance in nosocomial S. aureus isolates has been increasing dramatically in United States hospitals and is also associated with resistance to other useful antistaphylococcal compounds. Possible ways to decrease the incidence of nosocomial S. aureus infections include instituting more effective infection control, decreasing nasal colonization, developing vaccines, and developing new or improved antimicrobials.”, “author” : { “dropping-particle” : “”, “family” : “Archer”, “given” : “G L”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Infectious Diseases”, “id” : “ITEM-1”, “issue” : “5”, “issued” : { “date-parts” : “1998” }, “page” : “1179-1181”, “title” : “Staphylococcus aureus: A well-armed pathogen”, “type” : “article-journal”, “volume” : “26” }, “uris” : “http://www.mendeley.com/documents/?uuid=5ef1aeb2-056b-4754-a20a-f1c3d84a47ef” } , “mendeley” : { “formattedCitation” : “(Archer 1998)”, “plainTextFormattedCitation” : “(Archer 1998)”, “previouslyFormattedCitation” : “(Archer 1998)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Archer 1998). The character of those infections depends on numerous consideration, along with the pathogenic characteristics of the strain, host susceptibility and the path of access into the host. similarly, S. aureus infections vary in seriousness and outcome from minor pores and skin infections which includes superficial lesions (furuncles, boils) and wound infections, to life-threatening infections including septicemia, osteomyelitis, acute endocarditis and necrotizing pneumonia ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “ISBN” : “1712-9532 (Print)\r1712-9532 (Linking)”, “ISSN” : “1712-9532”, “PMID” : “19352449”, “abstract” : “Skin and soft tissue infections (SSTIs) involve microbial invasion of the skin and underlying soft tissues. They have variable presentations, etiologies and severities. The challenge of SSTIs is to efficiently differentiate those cases that require immediate attention and intervention, whether medical or surgical, from those that are less severe. Approximately 7% to 10% of hospitalized patients are affected by SSTIs, and they are very common in the emergency care setting. The skin has an extremely diverse ecology of organisms that may produce infection. The clinical manifestations of SSTIs are the culmination of a two-step process involving invasion and the interaction of bacteria with host defences. The cardinal signs of SSTIs involve the features of inflammatory response, with other manifestations such as fever, rapid progression of lesions and bullae. The diagnosis of SSTIs is difficult because they may commonly masquerade as other clinical syndromes. To improve the management of SSTIs, the development of a severity stratification approach to determine site of care and appropriate empirical treatment is advantageous. The selection of antimicrobial therapy is predicated on knowledge of the potential pathogens, the instrument of entry, disease severity and clinical complications. For uncomplicated mild to moderate infections, the oral route suffices, whereas for complicated severe infections, intravenous administration of antibiotics is warranted. Recognition of the potential for resistant pathogens causing SSTIs can assist in guiding appropriate selection of antibiotic therapy.”, “author” : { “dropping-particle” : “”, “family” : “Ki”, “given” : “Vincent”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rotstein”, “given” : “Coleman”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie meu0301dicale”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “2008” }, “page” : “173-84”, “title” : “Bacterial skin and soft tissue infections in adults: A review of their epidemiology, pathogenesis, diagnosis, treatment and site of care.”, “type” : “article-journal”, “volume” : “19” }, “uris” : “http://www.mendeley.com/documents/?uuid=3a96b4f4-1f2c-44f2-92db-ab4f07a9bbf4” } , “mendeley” : { “formattedCitation” : “(Ki and Rotstein 2008)”, “plainTextFormattedCitation” : “(Ki and Rotstein 2008)”, “previouslyFormattedCitation” : “(Ki and Rotstein 2008)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Ki and Rotstein 2008).

The virulence elements of S. aureus can be divided specifically into 3 clusters: cell surface-associated factors consisting of cell surface-bound proteins (the MSCRAMMs microbial surface components recognizing adhesive matrix molecules) and different surface-components (polysaccharide capsule & cell wall peptidoglycan); extracellular enzymes which includes coagulase and staphylokinase, and toxins which include haemolysins, leukocidins and toxic shock syndrome toxin (TSST) ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S1286-4579(01)01414-9”, “ISBN” : “1286-4579 (Print)\n1286-4579 (Linking)”, “ISSN” : “12864579”, “PMID” : “11418332”, “abstract” : “Variable genetic elements including plasmids, transposons and prophages are involved in pathogenesis and antibiotic resistance, and are an important component of the staphylococcal genome. This review covers a set of newly described variable chromosomal elements, pathogenicity and resistance islands, carrying superantigen and resistance genes, especially toxic shock and methicillin resistance, respectively. u00a9 2001 u00c9ditions scientifiques et mu00e9dicales Elsevier SAS.”, “author” : { “dropping-particle” : “”, “family” : “Novick”, “given” : “Richard P.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Schlievert”, “given” : “Patrick”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ruzin”, “given” : “Alexey”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Microbes and Infection”, “id” : “ITEM-1”, “issue” : “7”, “issued” : { “date-parts” : “2001” }, “page” : “585-594”, “title” : “Pathogenicity and resistance islands of staphylococci”, “type” : “article”, “volume” : “3” }, “uris” : “http://www.mendeley.com/documents/?uuid=49ce59c3-1f1e-4aa8-b383-411856523734”, “http://www.mendeley.com/documents/?uuid=f126e165-1d02-4631-8869-58d0e0c27f2e” } , “mendeley” : { “formattedCitation” : “(Novick, Schlievert, and Ruzin 2001)”, “plainTextFormattedCitation” : “(Novick, Schlievert, and Ruzin 2001)”, “previouslyFormattedCitation” : “(Novick, Schlievert, and Ruzin 2001)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Novick, Schlievert, and Ruzin 2001).

most S. aureus strains produce a capsular polysaccharide that contributes in virulence of S. aureus. The capsule performs critical role in the adhesion of bacterial cells to each other and to host tissues and medical device. further, the capsule inhibits phagocytosis and restricts the potential of antibiotics to attain the bacterial cell surface. furthermore, other cell wall components (e.g. peptidoglycan and lipoteichoic acid) have a role in S. aureus pathogenicity: peptidoglycan, for example, has endotoxin activity that stimulates macrophages to release cytokines ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1172/JCI200318535”, “ISBN” : “0021-9738 (Print)”, “ISSN” : “00219738”, “PMID” : “12727914”, “abstract” : “In the early 1970s, physicians were finally forced to abandon their belief that, given the vast array of effec- tive antimicrobial agents, virtually all bacterial infec- tions were treatable. Their optimism was shaken by the emergence of resistance to multiple antibiotics among such pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. The evolution of increasingly antimicrobial- resistant bacterial species stems from a multitude of factors that includes the widespread and sometimes inappropriate use of antimicrobials, the extensive use of these agents as growth enhancers in animal feed, and, with the increase in regional and international travel, the relative ease with which antimicrobial-resist- ant bacteria cross geographic barriers.”, “author” : { “dropping-particle” : “”, “family” : “Lowy”, “given” : “Franklin D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Clinical Investigation”, “id” : “ITEM-1”, “issue” : “9”, “issued” : { “date-parts” : “2003” }, “page” : “1265-1273”, “title” : “Antimicrobial resistance: The example of Staphylococcus aureus”, “type” : “article”, “volume” : “111” }, “uris” : “http://www.mendeley.com/documents/?uuid=6ecd8d43-b13c-47dd-b2c9-c3c791b25bce”, “http://www.mendeley.com/documents/?uuid=30504972-a6aa-479c-9721-e431f8cc1a44” } , “mendeley” : { “formattedCitation” : “(Lowy 2003)”, “plainTextFormattedCitation” : “(Lowy 2003)”, “previouslyFormattedCitation” : “(Lowy 2003)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Lowy 2003). Lipoteichoic acid (LTA) is notion to plays an crucial function in septic shock and different adverse host responses ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s11908-005-0043-8”, “ISBN” : “1190800500”, “ISSN” : “15233847”, “PMID” : “16225779”, “abstract” : “Staphylococcus aureus is a major human pathogen responsible for a variety of toxin-mediated and suppurative diseases. About 50 staphylococcal virulence factors have been described to date. In this review, we examine the clinical implications of key staphylococcal virulence factors in toxin-mediated diseases, septic shock, and severe focal infections such as arthritis, infective endocarditis, pneumonia acquired during mechanical ventilation, and necrotizing pneumonia. Staphylococcal pathogenicity is sometimes due principally to a single virulence factor, as in toxic shock syndrome and necrotizing pneumonia. In contrast, several virulence factors are involved in other staphylococcal disease, such as septic shock. A better knowledge of the mechanism of action of each virulence factor involved in the different staphylococcal diseases could open the way to the use of specific inhibitors in the clinical setting.”, “author” : { “dropping-particle” : “”, “family” : “Ferry”, “given” : “Tristan”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Perpoint”, “given” : “Thomas”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Vandenesch”, “given” : “Franu00e7ois”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Etienne”, “given” : “Jerome”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Current Infectious Disease Reports”, “id” : “ITEM-1”, “issue” : “6”, “issued” : { “date-parts” : “2005” }, “page” : “420-428”, “title” : “Virulence determinants in Staphylococcus aureus and their involvement in clinical syndromes”, “type” : “article”, “volume” : “7” }, “uris” : “http://www.mendeley.com/documents/?uuid=cd1378d8-22a7-4ce8-8b5f-054d6942a21f”, “http://www.mendeley.com/documents/?uuid=1011d107-9fac-4e5a-9f18-1846b72baeb8” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1128/CMR.18.3.521-540.2005”, “ISBN” : “0893-8512”, “ISSN” : “08938512”, “PMID” : “16020688”, “abstract” : “The gram-positive bacterium Staphylococcus aureus is a major pathogen responsible for a variety of diseases ranging from minor skin infections to life-threatening conditions such as sepsis. Cell wall-associated and secreted proteins (e.g., protein A, hemolysins, and phenol-soluble modulin) and cell wall components (e.g., peptidoglycan and alanylated lipoteichoic acid) have been shown to be inflammatory, and these staphylococcal components may contribute to sepsis. On the host side, many host factors have been implicated in the innate detection of staphylococcal components. One class of pattern recognition molecules, Toll-like receptor 2, has been shown to function as the transmembrane component involved in the detection of staphylococcal lipoteichoic acid and phenol-soluble modulin and is involved in the synthesis of inflammatory cytokines by monocytes/macrophages in response to these components. Nod2 (nucleotide-binding oligomerization domain 2) is the intracellular sensor for muramyl dipeptide, the minimal bioactive structure of peptidoglycan, and it may contribute to the innate immune defense against S. aureus. The staphylococcal virulence factor protein A was recently shown to interact directly with tumor necrosis factor receptor 1 in airway epithelium and to reproduce the effects of tumor necrosis factor alpha. Finally, peptidoglycan recognition protein L is an amidase that inactivates the proinflammatory activities of peptidoglycan. However, peptidoglycan recognition protein L probably plays a minor role in the innate immune response to S. aureus. Thus, several innate immunity receptors may be implicated in host defense against S. aureus.”, “author” : { “dropping-particle” : “”, “family” : “Fournier”, “given” : “Bu00e9nu00e9dicte”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Philpott”, “given” : “Dana J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Microbiology Reviews”, “id” : “ITEM-2”, “issue” : “3”, “issued” : { “date-parts” : “2005” }, “page” : “521-540”, “title” : “Recognition of Staphylococcus aureus by the innate immune system”, “type” : “article”, “volume” : “18” }, “uris” : “http://www.mendeley.com/documents/?uuid=bb248344-60f3-493c-870f-a4f91d97c4bb”, “http://www.mendeley.com/documents/?uuid=b99d03f5-84b8-40c7-aa33-b727136dc220” } , “mendeley” : { “formattedCitation” : “(Ferry et al. 2005; Fournier and Philpott 2005)”, “plainTextFormattedCitation” : “(Ferry et al. 2005; Fournier and Philpott 2005)”, “previouslyFormattedCitation” : “(Ferry et al. 2005; Fournier and Philpott 2005)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Ferry et al. 2005; Fournier and Philpott 2005).

Staphylococcal surface proteins make a contribution to the spread and virulence of S. aureus, those proteins, which consist of protein A, fibronectin binding proteins, fibrinogen binding proteins and collagen binding proteins are recognized MSCRAMMs. those proteins carry out an extensive spectrum of features and lots of recent studies have proven that those surface proteins play crucial roles in the potential of these bacteria to colonize host tissues ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1086/533591”, “ISBN” : “10.1086/533591”, “ISSN” : “1537-6591”, “PMID” : “18462090”, “abstract” : “Staphylococcus aureus is a versatile pathogen capable of causing a wide range of human diseases. However, the role of different virulence factors in the development of staphylococcal infections remains incompletely understood. Some clonal types are well equipped to cause disease across the globe, whereas others are facile at causing disease among community members. In this review, general aspects of staphylococcal pathogenesis are addressed, with emphasis on methicillin-resistant strains. Although methicillin-resistant S. aureus (MRSA) strains are not necessarily more virulent than methicillin-sensitive S. aureus strains, some MRSA strains contain factors or genetic backgrounds that may enhance their virulence or may enable them to cause particular clinical syndromes. We examine these pathogenic factors.”, “author” : { “dropping-particle” : “”, “family” : “Gordon”, “given” : “Rachel J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lowy”, “given” : “Franklin D”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical infectious diseases : an official publication of the Infectious Diseases Society of America”, “id” : “ITEM-1”, “issue” : “Suppl 5”, “issued” : { “date-parts” : “2008” }, “page” : “S350-9”, “title” : “Pathogenesis of methicillin-resistant Staphylococcus aureus infection.”, “type” : “article-journal”, “volume” : “46 Suppl 5” }, “uris” : “http://www.mendeley.com/documents/?uuid=8364ffae-31fd-4384-be1b-e3fc1c2f3ee6”, “http://www.mendeley.com/documents/?uuid=ae349e25-b8fd-4355-9828-ce6daae6364d” } , “mendeley” : { “formattedCitation” : “(Gordon and Lowy 2008)”, “plainTextFormattedCitation” : “(Gordon and Lowy 2008)”, “previouslyFormattedCitation” : “(Gordon and Lowy 2008)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Gordon and Lowy 2008). Throughout infection, S. aureus secretes an extensive type of extracellular enzymes and toxins that make a contribution either without delay or circuitously to pathogenesis. maximum, if no longer all S. aureus strains produce haemolysins, coagulases, nucleases, protease, lipases, hyaluronidase and collegenases ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/JCM.02402-06”, “ISBN” : “0095-1137 (Print)\r0095-1137 (Linking)”, “ISSN” : “00951137”, “PMID” : “17428929”, “abstract” : “We analyzed a representative sample of methicillin-resistant Staphylococcus aureus (MRSA) from 11 European countries (referred to as the HARMONY collection) using three molecular typing methods used within the HARMONY group to examine their usefulness for large, multicenter MRSA surveillance networks that use these different laboratory methodologies. MRSA isolates were collected based on their prevalence in each center and their genetic diversity, assessed by pulsed-field gel electrophoresis (PFGE). PFGE groupings (< or = 3 bands difference between patterns) were compared to those made by sequencing of the variable repeats in the protein A gene spa and clonal designations based on multilocus sequence typing (MLST), combined with PCR analysis of the staphylococcal chromosome cassette containing the mec genes involved in methicillin resistance (SCCmec). A high level of discrimination was achieved using each of the three methodologies, with discriminatory indices between 89.5% and 91.9% with overlapping 95% confidence intervals. There was also a high level of concordance of groupings made using each method. MLST/SCCmec typing distinguished 10 groups containing at least two isolates, and these correspond to the majority of nosocomial MRSA clones described in the literature. PFGE and spa typing resolved 34 and 31 subtypes, respectively, within these 10 MRSA clones, with each subtype differing only slightly from the most common pattern using each method. The HARMONY group has found that the methods used in this study differ in their availability and affordability to European centers involved in MRSA surveillance. Here, we demonstrate that the integration of such technologies is achievable, although common protocols (such as we have developed for PFGE) may also be important, as is the use of centralized Internet sites to facilitate data analysis. PFGE and spa-typing data from analysis of MRSA isolates from the many centers that have access to the relevant equipment can be compared to reference patterns/sequences, and clonal designations can be made. In the majority of cases, these will correspond to those made by the (more expensive) method of choice-MLST/SCCmec typing-and these alternative methods can therefore be used as frontline typing systems for multicenter surveillance of MRSA.”, “author” : { “dropping-particle” : “”, “family” : “Cookson”, “given” : “Barry D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Robinson”, “given” : “D. Ashley”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Monk”, “given” : “Alastair B.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Murchan”, “given” : “Stephen”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Deplano”, “given” : “Ariane”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ryck”, “given” : “Rafau00ebl”, “non-dropping-particle” : “De”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Struelens”, “given” : “Marc J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Scheel”, “given” : “Christina”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Fussing”, “given” : “Vivian”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Salmenlinna”, “given” : “Saara”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Vuopio-Varkila”, “given” : “Jaana”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Cuny”, “given” : “Christina”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Witte”, “given” : “Wolfgang”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tassios”, “given” : “Panayotis T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Legakis”, “given” : “Nikolas J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Leeuwen”, “given” : “Willem”, “non-dropping-particle” : “Van”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Belkum”, “given” : “Alex”, “non-dropping-particle” : “Van”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Vindel”, “given” : “Anna”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Garaizar”, “given” : “Javier”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Haeggman”, “given” : “Sara”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Olsson-Liljequist”, “given” : “Barbro”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ransjo”, “given” : “Ulrika”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Muller-Premru”, “given” : “Manica”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hryniewicz”, “given” : “Waleria”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rossney”, “given” : “Angela”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “O’Connell”, “given” : “Brian”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Short”, “given” : “Benjamin D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Thomas”, “given” : “Jonathan”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “O’Hanlon”, “given” : “Simon”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Enright”, “given” : “Mark C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Clinical Microbiology”, “id” : “ITEM-1”, “issue” : “6”, “issued” : { “date-parts” : “2007” }, “page” : “1830-1837”, “title” : “Evaluation of molecular typing methods in characterizing a European collection of epidemic methicillin-resistant Staphylococcus aureus strains: The HARMONY collection”, “type” : “article-journal”, “volume” : “45” }, “uris” : “http://www.mendeley.com/documents/?uuid=8d0f61d7-987a-4c7b-b795-efbc06ea66bb” } , “mendeley” : { “formattedCitation” : “(Cookson et al. 2007)”, “plainTextFormattedCitation” : “(Cookson et al. 2007)”, “previouslyFormattedCitation” : “(Cookson et al. 2007)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Cookson et al. 2007). Coagulase is produced exclusively, among the staphylococci, through almost all strains of S. aureus (except for some strains of S. intermedius). Coagulase reacts with blood-prothrombin to form a staphylothrombin complex that could convert fibrinogen to fibrin. even though, coagulase covers the bacterium with fibrin to reduce its susceptibility to host defenses, its contribution to pathogenesis isn’t always clear ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1159/000333447”, “ISBN” : “1662-8128 (Electronic)\r1662-811X (Linking)”, “ISSN” : “1662811X”, “PMID” : “22222316”, “abstract” : “Clinical isolates of Staphylococcus aureus secrete coagulases, polypeptides that bind to and activate prothrombin, thereby converting fibrinogen to fibrin and promoting the clotting of plasma or blood. Two staphylococcal products, the canonical coagulase (Coa) as well as the recently identified von Willebrand factor binding protein (vWbp), promote similar modifications of the coagulation cascade during host infection. Staphylococcal binding to fibrinogen or fibrin is an important attribute of disease pathogenesis, which leads to the formation of abscesses and bacterial persistence in host tissues and also enables the pathogen to cause lethal sepsis. Circumstantial evidence suggests that the product of coagulase activity, staphylococci captured within a fibrin meshwork, enable this pathogen to disseminate as thromboembolic lesions and to resist opsonophagocytic clearance by host immune cells. In addition, the coagulation products of staphylococci appear to display discrete differences when compared to those of thrombin-mediated coagulation, the latter representing a key innate defense mechanism against many invading pathogens. Preclinical evidence suggests that inactivation or neutralization of coagulases may prevent the pathogenesis of staphylococcal infections, a strategy that could be used to combat the current epidemic of hospital-acquired infections with drug-resistant S. aureus isolates.”, “author” : { “dropping-particle” : “”, “family” : “McAdow”, “given” : “Molly”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Missiakas”, “given” : “Dominique M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Schneewind”, “given” : “Olaf”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Innate Immunity”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “2012” }, “page” : “141-148”, “title” : “Staphylococcus aureus secretes coagulase and von willebrand factor binding protein to modify the coagulation cascade and establish host infections”, “type” : “article”, “volume” : “4” }, “uris” : “http://www.mendeley.com/documents/?uuid=eff943eb-7790-4509-93fb-b9d3ebbbaf65” } , “mendeley” : { “formattedCitation” : “(McAdow, Missiakas, and Schneewind 2012)”, “plainTextFormattedCitation” : “(McAdow, Missiakas, and Schneewind 2012)”, “previouslyFormattedCitation” : “(McAdow, Missiakas, and Schneewind 2012)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(McAdow, Missiakas, and Schneewind 2012). In other hand, Staphylokinase (Sak) is a plasminogen activator secreted by way of the majority of S. aureus strains. It forms complexes with trace quantities of plasmin found in host plasma ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/infdis/jiv360”, “ISBN” : “1537-6613 (Electronic)\r0022-1899 (Linking)”, “ISSN” : “15376613”, “PMID” : “26136471”, “abstract” : “Staphylococcus aureus biofilms, a leading cause of persistent infections, are highly resistant to immune defenses and antimicrobial therapies. In the present study, we investigated the contribution of fibrin and staphylokinase (Sak) to biofilm formation. In both clinical S. aureus isolates and laboratory strains, high Sak-producing strains formed less biofilm than strains that lacked Sak, suggesting that Sak prevents biofilm formation. In addition, Sak induced detachment of mature biofilms. This effect depended on plasminogen activation by Sak. Host-derived fibrin, the main substrate cleaved by Sak-activated plasminogen, was a major component of biofilm matrix, and dissolution of this fibrin scaffold greatly increased susceptibility of biofilms to antibiotics and neutrophil phagocytosis. Sak also attenuated biofilm-associated catheter infections in mouse models. In conclusion, our results reveal a novel role for Sak-induced plasminogen activation that prevents S. aureus biofilm formation and induces detachment of existing biofilms through proteolytic cleavage of biofilm matrix components.”, “author” : { “dropping-particle” : “”, “family” : “Kwiecinski”, “given” : “Jakub”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Peetermans”, “given” : “Marijke”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Liesenborghs”, “given” : “Laurens”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Na”, “given” : “Manli”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Bju00f6rnsdottir”, “given” : “Halla”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zhu”, “given” : “Xuefeng”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Jacobsson”, “given” : “Gunnar”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Johansson”, “given” : “Bengt R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Geoghegan”, “given” : “Joan A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Foster”, “given” : “Timothy J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Josefsson”, “given” : “Elisabet”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Bylund”, “given” : “Johan”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Verhamme”, “given” : “Peter”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Jin”, “given” : “Tao”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Infectious Diseases”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2016” }, “page” : “139-148”, “title” : “Staphylokinase control of staphylococcus aureus biofilm formation and detachment through host plasminogen activation”, “type” : “article-journal”, “volume” : “213” }, “uris” : “http://www.mendeley.com/documents/?uuid=abbf9d52-7f42-4460-b7e4-b9f17ce69c26” } , “mendeley” : { “formattedCitation” : “(Kwiecinski et al. 2016)”, “plainTextFormattedCitation” : “(Kwiecinski et al. 2016)”, “previouslyFormattedCitation” : “(Kwiecinski et al. 2016)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Kwiecinski et al. 2016). Those complexes sooner or later cleave plasminogen to form active plasmin, a powerful wide spectrum protease focused on host proteins, including fibrin clots. Plasminogen activation via Sak promotes bacterial entry and in addition spread within the pores and skin but it decreases the severity of invasive bloodstream infections ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/infdis/jit288”, “ISBN” : “1537-6613 (Electronic)\r0022-1899 (Linking)”, “ISSN” : “00221899”, “PMID” : “23801604”, “abstract” : “Skin infections are frequently caused by Staphylococcus aureus and can lead to a fatal sepsis. The microbial mechanisms controlling the initiation and progression from mild skin infection to a severe disseminated infection remain poorly understood. Using a combination of clinical data and in vitro and ex vivo assays, we show that staphylokinase, secreted by S. aureus, promoted the establishment of skin infections in humans and increased bacterial penetration through skin barriers by activating plasminogen. However, when infection was established, the interaction between staphylokinase and plasminogen did not promote systemic dissemination but induced the opening and draining of abscesses and decreased disease severity in neutropenic mice. Also, increased staphylokinase production was associated with noninvasive S. aureus infections in patients. Our results point out the dual roles of staphylokinase in S. aureus skin infections as promoting the establishment of infections while decreasing disease severity.”, “author” : { “dropping-particle” : “”, “family” : “Kwiecinski”, “given” : “Jakub”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Jacobsson”, “given” : “Gunnar”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Karlsson”, “given” : “Maria”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zhu”, “given” : “Xuefeng”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Wang”, “given” : “Wanzhong”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Bremell”, “given” : “Tomas”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Josefsson”, “given” : “Elisabet”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Jin”, “given” : “Tao”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Infectious Diseases”, “id” : “ITEM-1”, “issue” : “6”, “issued” : { “date-parts” : “2013” }, “page” : “990-999”, “title” : “Staphylokinase promotes the establishment of staphylococcus aureus skin infections while decreasing disease severity”, “type” : “paper-conference”, “volume” : “208” }, “uris” : “http://www.mendeley.com/documents/?uuid=b6f4ab49-0733-4e30-9325-3c5e90608117” } , “mendeley” : { “formattedCitation” : “(Kwiecinski et al. 2013)”, “plainTextFormattedCitation” : “(Kwiecinski et al. 2013)”, “previouslyFormattedCitation” : “(Kwiecinski et al. 2013)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Kwiecinski et al. 2013).

Moreover, other enzymes secreted by S. aureus encompass proteases consisting of serine protease V8 and lipases that breakdown the bactericidal fatty acids produced by infected cells. Many S. aureus strains produce hyaluronidase that can degrade the hyaluronic acid, a component of the extracellular matrix of host tissues, and enables the bacterium to unfold thru host tissues. Hyaluronidase is typically referred because the spreading issue ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0378-1097(99)00669-2”, “ISBN” : “0378-1097 (Print) 0378-1097 (Linking)”, “ISSN” : “03781097”, “PMID” : “10675584”, “abstract” : “Bacterial hyaluronidases, enzymes capable of breaking down hyaluronate, are produced by a number of pathogenic Gram-positive bacteria that initiate infections at the skin or mucosal surfaces. Since reports of the hyaluronidases first appeared, there have been numerous suggestions as to the role of the enzyme in the disease process. Unlike some of the other more well studied virulence factors, much of the information on the role of hyaluronidase is speculative, with little or no data to substantiate proposed roles. Over the last 5 years, a number of these enzymes from Gram-positive organisms have been cloned, and the nucleotide sequence determined. Phylogenetic analysis, using the deduced amino acid sequences of the Gram-positive hyaluronidases, suggests a relatedness among some of the enzymes. Molecular advances may lead to a more thorough understanding of the role of hyaluronidases in bacterial physiology and pathogenesis. Copyright (C) 2000 Federation of European Microbiological Societies.”, “author” : { “dropping-particle” : “”, “family” : “Hynes”, “given” : “Wayne L.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Walton”, “given” : “Sheryl Lynne”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “FEMS Microbiology Letters”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “2000” }, “page” : “201-207”, “title” : “Hyaluronidases of Gram-positive bacteria”, “type” : “article”, “volume” : “183” }, “uris” : “http://www.mendeley.com/documents/?uuid=3775c83d-0c91-468c-ac9e-50b5a3186643” } , “mendeley” : { “formattedCitation” : “(Hynes and Walton 2000)”, “plainTextFormattedCitation” : “(Hynes and Walton 2000)”, “previouslyFormattedCitation” : “(Hynes and Walton 2000)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Hynes and Walton 2000). The DNA and RNA of host cells are degraded by nucleases. these enzymes nearly produced by all Staphylococcal strains and cleave the phosphodiester bonds of each single and double stranded DNA and RNA ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.3390/s140712437”, “ISBN” : “1424-8220”, “ISSN” : “14248220”, “PMID” : “25019631”, “abstract” : “Nucleolytic enzymes are associated with various diseases, and several methods have been developed for their detection. DNase expression is modulated in such diseases as acute myocardial infarction, transient myocardial ischemia, oral cancer, stomach cancer, and malignant lymphoma, and DNase I is used in cystic fibroma therapy. RNase is used to treat mesothelial cancer because of its antiproliferative, cytotoxic, and antineoplastic activities. Angiogenin, an angiogenic factor, is a member of the RNase A family. Angiogenin inhibitors are being developed as anticancer drugs. In this review, we describe fluorometric and electrochemical techniques for detecting DNase and RNase in disease. Oligonucleotides having fluorescence resonance energy transfer (FRET)-causing chromophores are non-fluorescent by themselves, yet become fluorescent upon cleavage by DNase or RNase. These oligonucleotides serve as a powerful tool to detect activities of these enzymes and provide a basis for drug discovery. In electrochemical techniques, ferrocenyl oligonucleotides with or without a ribonucleoside unit are used for the detection of RNase or DNase. This technique has been used to monitor blood or serum samples in several diseases associated with DNase and RNase and is unaffected by interferents in these sample types.”, “author” : { “dropping-particle” : “”, “family” : “Sato”, “given” : “Shinobu”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Takenaka”, “given” : “Shigeori”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Sensors (Switzerland)”, “id” : “ITEM-1”, “issue” : “7”, “issued” : { “date-parts” : “2014” }, “page” : “12437-12450”, “title” : “Highly sensitive nuclease assays based on chemically modified DNA or RNA”, “type” : “article”, “volume” : “14” }, “uris” : “http://www.mendeley.com/documents/?uuid=c4ddab66-8233-437c-8e9c-3df0fe9ea871” } , “mendeley” : { “formattedCitation” : “(Sato and Takenaka 2014)”, “plainTextFormattedCitation” : “(Sato and Takenaka 2014)”, “previouslyFormattedCitation” : “(Sato and Takenaka 2014)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Sato and Takenaka 2014). Finally, S. aureus strains can produce ?-lactamases that are liable for the resistance of ?-lactam antibiotics ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1186/s13104-017-2710-x”, “ISSN” : “1756-0500”, “PMID” : “28797299”, “abstract” : “Objective: Antimicrobial resistance is an increasing global health problem. Very little data on resistance patterns of pathogenic bacteria in low-income countries exist. The aim of this study was to measure the prevalence of antimicrobial drug resistant bacteria carried by in- and outpatients in the resource constraint setting of a secondary care hospital in Zambia. Nasal and rectal samples from 50 in- and 50 outpatients were collected. Patients were randomly selected and informed consent was obtained. Nasal samples were tested for the presence of methicillin-resistant Staphylococcus aureus (MRSA), and rectal samples for Gram-negative rods (family of Enterobacteriaceae) non-susceptible to gentamicin, ciprofloxacin and ceftriaxone. Additionally, E-tests were performed on ceftriaxone-resistant Enterobacteriaceae to detect extended-spectrum u03b2-lactamases (ESBLs).; Results: 14% of inpatients carried S. aureus, and 18% of outpatients. No MRSA was found. 90% of inpatients and 48% of outpatients carried one or more Enterobacteriaceae strains (75% Escherichia coli and Klebsiella pneumonia) resistant to gentamicin, ciprofloxacin and/or ceftriaxone (pu00a0<u00a00.001). Among inpatients gentamicin resistance was most prevalent (in 78%), whereas among outpatients ciprofloxacin resistance prevailed (in 38%). All ceftriaxone-resistant Enterobacteriaceae were ESBL-positive; these were present in 52% of inpatients versus 12% of outpatients (pu00a0<u00a00.001). We conclude it is feasible to perform basic microbiological procedures in the hospital laboratory in a low-income country and generate data on antimicrobial susceptibility. The high prevalence of antimicrobial drug resistant Enterobacteriaceae carried by in- and outpatients is worrisome. In order to slow down antimicrobial resistance, surveillance data on local susceptibility patterns of bacteria are a prerequisite to generate guidelines for antimicrobial therapy, to guide in individual patient treatment and to support implementation of infection control measures in a hospital.;”, “author” : { “dropping-particle” : “”, “family” : “Nagelkerke”, “given” : “Marjolijn M. B.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Sikwewa”, “given” : “Kapembwa”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Makowa”, “given” : “Dennis”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Vries”, “given” : “Irene”, “non-dropping-particle” : “de”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chisi”, “given” : “Simon”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dorigo-Zetsma”, “given” : “J. Wendelien”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “BMC Research Notes”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2017” }, “page” : “378”, “title” : “Prevalence of antimicrobial drug resistant bacteria carried by in- and outpatients attending a secondary care hospital in Zambia”, “type” : “article-journal”, “volume” : “10” }, “uris” : “http://www.mendeley.com/documents/?uuid=f11fc3e3-8871-4ec6-9313-cbb75b1614ac” } , “mendeley” : { “formattedCitation” : “(Nagelkerke et al. 2017)”, “plainTextFormattedCitation” : “(Nagelkerke et al. 2017)”, “previouslyFormattedCitation” : “(Nagelkerke et al. 2017)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Nagelkerke et al. 2017).

Antibiotic resistance:As the late 1940s, antibiotics resistance related to hospital acquired infections has arisen as a crucial issue worldwide. on this matter, it’s miles critical to differentiate among bacterial strains acquired in hospitals from the ones obtained in the community, since the earlier are more likely to exhibit an extra variety of antibiotic resistances than the latter ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1186/1744-8603-2-6”, “ISBN” : “1744-8603 (Electronic)\r1744-8603 (Linking)”, “ISSN” : “17448603”, “PMID” : “16603071”, “abstract” : “BACKGROUND: Antimicrobial resistance is an under-appreciated threat to public health in nations around the globe. With globalization booming, it is important to understand international patterns of resistance. If countries already experience similar patterns of resistance, it may be too late to worry about international spread. If large countries or groups of countries that are likely to leap ahead in their integration with the rest of the world–China being the standout case–have high and distinctive patterns of resistance, then a coordinated response could substantially help to control the spread of resistance. The literature to date provides only limited evidence on these issues. METHODS: We study the recent patterns of antibiotic resistance in three geographically separated, and culturally and economically distinct countries–China, Kuwait and the United States–to gauge the range and depth of this global health threat, and its potential for growth as globalization expands. Our primary measures are the prevalence of resistance of specific bacteria to specific antibiotics. We also propose and illustrate methods for aggregating specific “bug-drug” data. We use these aggregate measures to summarize the resistance pattern for each country and to study the extent of correlation between countries’ patterns of drug resistance. RESULTS: We find that China has the highest level of antibiotic resistance, followed by Kuwait and the U.S. In a study of resistance patterns of several most common bacteria in China in 1999 and 2001, the mean prevalence of resistance among hospital-acquired infections was as high as 41% (with a range from 23% to 77%) and that among community- acquired infections was 26% (with a range from 15% to 39%). China also has the most rapid growth rate of resistance (22% average growth in a study spanning 1994 to 2000). Kuwait is second (17% average growth in a period from 1999 to 2003), and the U.S. the lowest (6% from 1999 to 2002). Patterns of resistance across the three countries are not highly correlated; the most correlated were China and Kuwait, followed by Kuwait and the U.S., and the least correlated pair was China and the U.S. CONCLUSION: Antimicrobial resistance is a serious and growing problem in all three countries. To date, there is not strong international convergence in the countries’ resistance patterns. This finding may change with the greater international travel that will accompany globalization. Future research on the deu2026″, “author” : { “dropping-particle” : “”, “family” : “Zhang”, “given” : “Ruifang”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Eggleston”, “given” : “Karen”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rotimi”, “given” : “Vincent”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zeckhauser”, “given” : “Richard J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Globalization and Health”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2006” }, “title” : “Antibiotic resistance as a global threat: Evidence from China, Kuwait and the United States”, “type” : “article-journal”, “volume” : “2” }, “uris” : “http://www.mendeley.com/documents/?uuid=f9d44ff1-50cf-4469-aa63-68dc57c8c2fa” } , “mendeley” : { “formattedCitation” : “(Zhang et al. 2006)”, “plainTextFormattedCitation” : “(Zhang et al. 2006)”, “previouslyFormattedCitation” : “(Zhang et al. 2006)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Zhang et al. 2006). Penicillin resistant strains of S. aureus were first detected within the 1940s, quickly after this antibiotic became introduced into scientific practice ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1038/nrmicro2200”, “ISBN” : “1740-1526”, “ISSN” : “17401526”, “PMID” : “19680247”, “abstract” : “Staphylococcus aureus is notorious for its ability to become resistant to antibiotics. Infections that are caused by antibiotic-resistant strains often occur in epidemic waves that are initiated by one or a few successful clones. Methicillin-resistant S. aureus (MRSA) features prominently in these epidemics. Historically associated with hospitals and other health care settings, MRSA has now emerged as a widespread cause of community infections. Community or community-associated MRSA (CA-MRSA) can spread rapidly among healthy individuals. Outbreaks of CA-MRSA infections have been reported worldwide, and CA-MRSA strains are now epidemic in the United States. Here, we review the molecular epidemiology of the epidemic waves of penicillin- and methicillin-resistant strains of S. aureus that have occurred since 1940, with a focus on the clinical and molecular epidemiology of CA-MRSA.”, “author” : { “dropping-particle” : “”, “family” : “Chambers”, “given” : “Henry F.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “DeLeo”, “given” : “Frank R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Nature Reviews Microbiology”, “id” : “ITEM-1”, “issue” : “9”, “issued” : { “date-parts” : “2009” }, “page” : “629-641”, “title” : “Waves of resistance: Staphylococcus aureus in the antibiotic era”, “type” : “article”, “volume” : “7” }, “uris” : “http://www.mendeley.com/documents/?uuid=f1161e1c-7a17-4499-82e6-ad8a4cd67248” } , “mendeley” : { “formattedCitation” : “(Chambers and DeLeo 2009)”, “plainTextFormattedCitation” : “(Chambers and DeLeo 2009)”, “previouslyFormattedCitation” : “(Chambers and DeLeo 2009)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Chambers and DeLeo 2009). This resistance was due to the creation of ?- lactamases which inactivate the antibiotic through hydrolyzing the ?-lactam ring. the principle mechanism of penicillin resistance is through the blaZ-encodes ?-lactamases ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/s00203-002-0436-0”, “ISBN” : “0302-8933 (Print)\r0302-8933 (Linking)”, “ISSN” : “03028933”, “PMID” : “12189417”, “abstract” : “Methicillin resistance in staphylococci is due to an acquired penicillin-binding protein, PBP2′ (PBP2a). This additional PBP, encoded by mecA, confers an intrinsic resistance to all beta-lactams and their derivatives. Resistance levels in methicillin-resistant Staphylococcus aureus (MRSA) depend on efficient PBP2′ production and are modulated by chromosomal factors. Depending on the genetic background of the strain that acquired mecA, resistance levels range from phenotypically susceptible to highly resistant. Characteristic for most MRSA is the heterogeneous expression of resistance, which is due to the segregation of a more highly resistant subpopulation upon challenge with methicillin. Maximal expression of resistance by PBP2′ requires the efficient and correct synthesis of the peptidoglycan precursor. Genes involved in cell-wall precursor formation and turnover, regulation, transport, and signal transduction may determine the level of resistance that is expressed. At this stage, however, there is no information available on the functionality or efficacy of such factors in clinical isolates in relation to methicillin resistance levels.”, “author” : { “dropping-particle” : “”, “family” : “Berger-Bu00e4chi”, “given” : “Brigitte”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rohrer”, “given” : “Susanne”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Archives of Microbiology”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2002” }, “page” : “165-171”, “title” : “Factors influencing methicillin resistance in staphylococci”, “type” : “article”, “volume” : “178” }, “uris” : “http://www.mendeley.com/documents/?uuid=3cfcde37-906a-471b-8476-aa41857f53ae” } , “mendeley” : { “formattedCitation” : “(Berger-Bu00e4chi and Rohrer 2002)”, “plainTextFormattedCitation” : “(Berger-Bu00e4chi and Rohrer 2002)”, “previouslyFormattedCitation” : “(Berger-Bu00e4chi and Rohrer 2002)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Berger-Bächi and Rohrer 2002). The mechanism is illustrated in Figure 2.

Presently, 90% of S. aureus isolates are penicillin-resistant and resistance is mainly linked with hospitals. consequently, new generations of penicillins had been advanced. The advent of methicillin in the 1960s became observed hastily by way of the emergence of methicillin-resistant isolates. Methicillin-resistance is mediated by production of an altered penicillin binding protein (PBP2a) that has a low affinity for ?-lactam antibiotics ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0195-6701(98)90020-2”, “ISBN” : “0195-6701”, “ISSN” : “01956701”, “PMID” : “9777517”, “abstract” : “The resistance of bacteria to antibiotics, particularly those used for first-line therapy, is an increasing cause for concern. In the UK, the prevalence of resistance to methicillin and mupirocin in Staphylococcus aureus, and to penicillin and macrolides in Streptococcus pneumoniae, appear to be increasing. There has also been an increase in the number of hospitals where glycopeptide-resistant enterococci are known to have been isolated. The increases in methicillin-resistant S. aureus and glycopeptide-resistant enterococci are due, in part, to the inter-hospital spread of epidemic strains. Although new quinolones and streptogramins with activity against Gram-positive bacteria (including strains resistant to currently available agents) are under development, there is no reason to believe that resistance to these agents will not emerge. The control of resistance in Gram-positive bacteria will require a multi-faceted approach, including continued and improved surveillance, a reduction in the unnecessary use of antibiotics, and the application of other strategies such as vaccination.”, “author” : { “dropping-particle” : “”, “family” : “Johnson”, “given” : “A. P.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Hospital Infection”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “1998” }, “page” : “17-26”, “title” : “Antibiotic resistance among clinically important Gram-positive bacteria in the UK”, “type” : “article”, “volume” : “40” }, “uris” : “http://www.mendeley.com/documents/?uuid=cf7195ea-af89-4a9f-88ba-41ccd754ff6c” } , “mendeley” : { “formattedCitation” : “(A. P. Johnson 1998)”, “plainTextFormattedCitation” : “(A. P. Johnson 1998)”, “previouslyFormattedCitation” : “(A. P. Johnson 1998)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(A. P. Johnson 1998). The 1960s additionally saw an improvement of non-?-lactam antibiotics consisting of streptomycin chloramphenicol, erythromycin, and tetracycline. despite the fact that first of all effective against S. aureus, however resistance against them evolved swiftly. by means of 1976, resistance to kanamycin and gentamicin occurred and reported and, via the early of 1980s, multiresistant S. aureus strains were reportedly chargeable for nosocomial outbreaks in many countries ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/AAC.33.8.1335”, “ISBN” : “0066-4804 (Print)\r0066-4804 (Linking)”, “ISSN” : “00664804”, “PMID” : “2552907”, “abstract” : “Homologous genes encoding resistance to gentamicin, tobramycin, and kanamycin through the bifunctional acetylating AAC(6′) and phosphorylating APH(2″) aminoglycoside-modifying enzyme were identified in staphylococci isolated from patients in the United States. The mobility of gentamicin resistance (Gmr) genes found on a prototype conjugative plasmid (pGO1) was compared with that of genes cloned from chromosomal sites. Plasmid-encoded Gmr genes and flanking sequences were introduced onto a temperature-sensitive plasmid (pRN3208) from pGO1 by homologous recombination between insertion sequence-like elements present on both replicons. Growth of Staphylococcus aureus strains containing the temperature-sensitive recombinant (pGO161) at the nonpermissive temperature for plasmid replication (42 degrees C) revealed no translocation of Gmr from its plasmid location. A transposon (Tn551) resident on the same replicon did translocate. Chromosomal Gmr determinants were cloned, together with the gene for trimethoprim resistance (dfrA), from three geographically distinct S. epidermidis isolates; two were subcloned onto temperature-sensitive Escherichia coli-S. aureus shuttle plasmids as 7.2-kilobase BglII fragments. Growth of both recombination-deficient and-proficient S. aureus strains containing the cloned genes at 42 degrees C allowed detection of transposition of Gmr sequences and identification of insertion into random chromosomal sites. We have designated this 5-kilobase transposon from S. epidermidis as Tn4031.”, “author” : { “dropping-particle” : “”, “family” : “Thomas”, “given” : “W. D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Archer”, “given” : “G. L.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Antimicrobial Agents and Chemotherapy”, “id” : “ITEM-1”, “issue” : “8”, “issued” : { “date-parts” : “1989” }, “page” : “1335-1341”, “title” : “Mobility of gentamicin resistance genes from staphylococci isolated in the United States: Identification of Tn4031, a gentamicin resistance transposon from Staphylococcus epidermidis”, “type” : “article-journal”, “volume” : “33” }, “uris” : “http://www.mendeley.com/documents/?uuid=8df4d27a-67db-4234-8e87-1d0b4e2529e1” }, { “id” : “ITEM-2”, “itemData” : { “ISSN” : “1551-4056”, “PMID” : “28656013”, “abstract” : “The evolution of Staphylococcus aureus during the modern antibiotic era has been delineated by distinct strain emergence events, many of which include acquisition of antibiotic resistance. The relative high burden of methicillin-resistant S. aureus (MRSA) in healthcare and community settings is a major concern worldwide. Vancomycin, a glycopeptide antibiotic that inhibits cell wall biosynthesis, remains a drug of choice for treatment of severe MRSA infections. S. aureus strains exhibiting increased resistance to vancomycin, known as vancomycin intermediate-resistant S. aureus (VISA) (MIC = 4-8 u00b5g/mL), were discovered in the 1990s. The molecular basis of resistance in VISA is polygenic and involves stepwise mutations in genes encoding molecules predominantly involved in cell envelope biosynthesis. S. aureus isolates with complete resistance to vancomycin (MIC u2265 16 u00b5g/mL) are termed vancomycin-resistant S. aureus (VRSA)-they were first reported in the U.S. in 2002. Resistance in VRSA is conferred by the vanA gene and operon, which is present on a plasmid. Although treatment of VRSA infections is challenging, the total number of human VRSA infections to date is limited (14 in the U.S.). By comparison, the burden of VISA is relatively high and the molecular mechanisms of resistance are less well-defined. VISA are associated with persistent infections, vancomycin treatment failure, and poor clinical outcomes. Here, we review in brief progress made toward understanding the acquisition of antibiotic resistance in S. aureus, with an emphasis on the molecular mechanisms underlying vancomycin resistance.”, “author” : { “dropping-particle” : “”, “family” : “McGuinness”, “given” : “Will A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Malachowa”, “given” : “Natalia”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “DeLeo”, “given” : “Frank R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Yale journal of biology and medicine”, “id” : “ITEM-2”, “issue” : “2”, “issued” : { “date-parts” : “2017” }, “page” : “269-281”, “title” : “Vancomycin Resistance in Staphylococcus aureus .”, “type” : “article-journal”, “volume” : “90” }, “uris” : “http://www.mendeley.com/documents/?uuid=d55679b5-3d44-43ca-abc8-d098d72d6416” } , “mendeley” : { “formattedCitation” : “(McGuinness, Malachowa, and DeLeo 2017; Thomas and Archer 1989)”, “plainTextFormattedCitation” : “(McGuinness, Malachowa, and DeLeo 2017; Thomas and Archer 1989)”, “previouslyFormattedCitation” : “(McGuinness, Malachowa, and DeLeo 2017; Thomas and Archer 1989)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(McGuinness, Malachowa, and DeLeo 2017; Thomas and Archer 1989). A timeline illustrating emergence of antibiotic-resistant S. aureus following the introduction of key antibiotics is provided in figure 1.

Figure SEQ Figure * ARABIC 1-Staphylococcus aureus Drug Resistance and Epidemics.Vancomycin and teicoplanin are glycopeptide antibiotics were the first drug of choice for the treatment of serious nosocomial MRSA infections for the past fifteen years. Since the emergence of vancomycin-resistant enterococci, completely vancomycin resistant strains of S. aureus were anticipated. In 1996, the first vancomycin-intermediate resistant S. aureus (VISA) reported in Japan and this isolate, titled Mu50, had an minimum inhibitory concentration (MIC) for vancomycin of 8?g/ml ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/jac/40.1.135”, “ISBN” : “0305-7453 (Print)\r0305-7453 (Linking)”, “ISSN” : “03057453”, “PMID” : “13545234”, “abstract” : “Objective: To study markers of progression in a cohort of HIV-infected intravenous drug users (IDU). Design: A prospective epidemiologic study. Setting and patients. We studied progression of HIV infection among 126 IDU attending the Municipal Health Service in Amsterdam. Main outcome measures: Progression was defined as a decline of the CD4 cell count to 30 years relative hazard (RH), 7.7 95% confidence intervals (CI), 1.7-36.0, core antibody negativity RH, 5.3 (95% Cl, 1.6-17.6), CD4 cell count for CD4 cells 350-500 x 10(6)/l, RH, 1.38 (95% Cl, 0.37-5.16); for CD4 cells 200-350 x 10(6)/l, RH, 9.20 (95% Cl, 2.73-31.05) compared with a CD4 count > 500 x 10(6)/l. A lower rate of progression was associated with borrowing used injecting equipment. IDU who reported borrowing injecting equipment between 1980 and baseline 10-99 times or >99 times had a RH of 0.44 (95% Cl, 0.22-0.88) and 0.19 (95% Cl, 0.03-0.37), respectively, compared with IDU who had borrowed <10 times. p24 antigen positivity was more predictive than core antibody negativity in a model with time-dependent variables, the relative risk for p24 antigen-positive participants was 3.5 (95% Cl, 1.3-9.3). Additional analysis of progression to AIDS in a larger group of IDU showed comparable results with regard to the effect of borrowing on progression. Conclusions: Our observation that those IDU who reported borrowing injecting equipment most frequently appeared to have the lowest rate of progression, corrected for some sources of potential confounding, requires further epidemiologic confirmation and extended laboratory studies since other sources of bias might have been present. Baseline CD4 count, age and core antibody or p24 antigen were predictive of progression in IDU. We wish to emphasize that our results do not imply that borrowing should be encouraged, but may have implications for our understanding of HIV pathogenesis.”, “author” : { “dropping-particle” : “”, “family” : “Hiramatsu”, “given” : “K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hanaki”, “given” : “H.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ino”, “given” : “T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Yabuta”, “given” : “K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Oguri”, “given” : “T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tenover”, “given” : “F. C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Antimicrobial Chemotherapy”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “1997” }, “page” : “135-136”, “title” : “Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility 1”, “type” : “article”, “volume” : “40” }, “uris” : “http://www.mendeley.com/documents/?uuid=07357655-673a-471b-8bb5-c5ce18b2e43d” } , “mendeley” : { “formattedCitation” : “(K. Hiramatsu et al. 1997)”, “plainTextFormattedCitation” : “(K. Hiramatsu et al. 1997)”, “previouslyFormattedCitation” : “(K. Hiramatsu et al. 1997)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(K. Hiramatsu et al. 1997). Consequently, clinical cases from which VISA have been remoted were reported in 1997 in United States of America, then France and later within the United Kingdom. These types of suggested isolates have been vancomycin-intermediate S. aureus (VISA) and were called glycopeptide-intermediate S. aureus (GISA) ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S1473-3099(01)00091-3”, “ISBN” : “1473-3099 (Print)”, “ISSN” : “14733099”, “PMID” : “11871491”, “abstract” : “Vancomycin has been the most reliable therapeutic agent against infections caused by meticillin-resistant Staphylococcus aureus (MRSA). However, in 1996 the first MRSA to acquire resistance to vancomycin, was isolated from a Japanese patient. The patient had contracted a post-operative wound infection that was refractory to long-term vancomycin therapy. Subsequent isolation of several vancomycin resistant S aureus (VRSA) strains from USA, France, Korea, South Africa, and Brazil has confirmed that emergence of vancomycin resistance in S aureus is a global issue. A certain group of S aureus, designated hetero-VRSA, frequently generate VRSA upon exposure to vancomycin, and are associated with infections that are potentially refractory to vancomycin therapy. Presence of hetero-VRSA may be an important indicator of the insidious decline of the clinical effectiveness of vancomycin in the hospitals. Vancomycin resistance is acquired by mutation and thickening of cell wall due to accumulation of excess amounts of peptidoglycan. This seems to be a common resistance mechanism for all VRSA strains isolated in the world so far. u00a9 2001 Elsevier Science Ltd.”, “author” : { “dropping-particle” : “”, “family” : “Hiramatsu”, “given” : “Keiichi”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Lancet Infectious Diseases”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2001” }, “page” : “147-155”, “title” : “Vancomycin-resistant Staphylococcus aureus: A new model of antibiotic resistance”, “type” : “article”, “volume” : “1” }, “uris” : “http://www.mendeley.com/documents/?uuid=cb97acc1-8508-4e09-9879-ebffd070efb1” } , “mendeley” : { “formattedCitation” : “(Keiichi Hiramatsu 2001)”, “plainTextFormattedCitation” : “(Keiichi Hiramatsu 2001)”, “previouslyFormattedCitation” : “(Keiichi Hiramatsu 2001)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Keiichi Hiramatsu 2001).
The National Committee for Clinical laboratory standard (NCCLS) suggested the definition for vancomycin-resistant terms to avoid any confusion. S. aureus strains that have an (MIC) of 4 ?g/ml or below of vancomycin are defined as vancomycin-sensitive S. aureus (VSSA), while those have an MIC of between 8-16 ?g/ml as vancomycin-intermediate S. aureus (VISA), and those that have an MIC of 32 ?g/ml or more as vancomycin-resistant S. aureus (VRSA) ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/CMR.15.3.430-438.2002”, “ISBN” : “0893-8512 (Print)\r0893-8512 (Linking)”, “ISSN” : “08938512”, “PMID” : “11294734”, “abstract” : “Recent emergence of vancomycin resistance in methicillin-resistant Staphylococcus aureus (VRSA) has posed a new threat to hospital infection control and antibiotic chemotherapy. Relatively low-level resistance of VRSA compared to that of vancomycin-resistant enterococci (VRE), and prevalence of S. aureus clinical strains heterogeneously resistant to vancomycin (hetero-VRSA), challenge the value of routine antibiotic susceptibility tests as a tool for the prediction of clinical efficacy of vancomycin therapy. This review summarizes the history of emergence of glycopeptide resistance in staphylococci and considers the mechanism of resistance in these organisms. u00a9 1998 Harcourt Brace & Co. Ltd All rights reserved.”, “author” : { “dropping-particle” : “”, “family” : “Srinivasan”, “given” : “Arjun”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dick”, “given” : “James D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Perl”, “given” : “Trish M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Microbiology Reviews”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2002” }, “page” : “430-438”, “title” : “Vancomycin resistance in Staphylococci”, “type” : “article”, “volume” : “15” }, “uris” : “http://www.mendeley.com/documents/?uuid=a11991b9-9a7e-456b-98ed-ddbf96e2145a” } , “mendeley” : { “formattedCitation” : “(Srinivasan, Dick, and Perl 2002)”, “plainTextFormattedCitation” : “(Srinivasan, Dick, and Perl 2002)”, “previouslyFormattedCitation” : “(Srinivasan, Dick, and Perl 2002)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Srinivasan, Dick, and Perl 2002). However, the first fully vancomycin-resistant S. aureus (VRSA) isolate discovered in the year 2002, from a renal dialysis patient in Michigan, USA ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1001/jama.288.7.824”, “ISBN” : “0149-2195 (Print)\r0149-2195 (Linking)”, “ISSN” : “0149-2195”, “PMID” : “12139181”, “abstract” : “Staphylococcus aureus is a cause of hospital- and community-acquired infections. In 1996, the first clinical isolate of S. aureus with reduced susceptibility to vancomycin was reported from Japan. The vancomycin minimum inhibitory concentration (MIC) result reported for this isolate was in the intermediate range (vancomycin MIC=8 microg/mL) using interpretive criteria defined by the National Committee for Clinical Laboratory Standards. As of June 2002, eight patients with clinical infections caused by vancomycin-intermediate S. aureus (VISA) have been confirmed in the United States. This report describes the first documented case of infection caused by vancomycin-resistant S. aureus (VRSA) (vancomycin MIC > or = 32 microg/mL) in a patient in the United States. The emergence of VRSA underscores the need for programs to prevent the spread of antimicrobial-resistant microorganisms and control the use of antimicrobial drugs in health-care settings.”, “author” : { “dropping-particle” : “”, “family” : “Committee”, “given” : “National”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “States”, “given” : “United”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “April”, “given” : “Since”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Vrsa”, “given” : “The”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “MMWR. Morbidity and mortality weekly report”, “id” : “ITEM-1”, “issue” : “26”, “issued” : { “date-parts” : “2002” }, “page” : “565-7”, “title” : “Staphylococcus aureus resistant to vancomycin–United States, 2002.”, “type” : “article-journal”, “volume” : “51” }, “uris” : “http://www.mendeley.com/documents/?uuid=f519d308-a8ff-4ef9-84f1-707bfc083444” } , “mendeley” : { “formattedCitation” : “(Committee et al. 2002)”, “plainTextFormattedCitation” : “(Committee et al. 2002)”, “previouslyFormattedCitation” : “(Committee et al. 2002)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Committee et al. 2002) with MIC of >128 ?g/ml and carried the vancomycin-resistance gene, vanA ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1056/NEJMoa025025”, “ISBN” : “1533-4406 (Electronic)\r0028-4793 (Linking)”, “ISSN” : “1533-4406”, “PMID” : “12672861”, “abstract” : “Until recently, vancomycin was the only uniformly effective treatment for staphylococcal infections. In 1997, the first clinical isolate of Staphylococcus aureus with reduced susceptibility to vancomycin was reported,1 and as of June 2002, eight confirmed infections with such strains had been reported in patients in the United States.2-6 The minimal inhibitory concentrations (MICs) of vancomycin reported for these isolates are in the intermediate range (8 to 16 u03bcg per milliliter) according to interpretive criteria defined by the National Committee for Clinical Laboratory Standards.7 In June 2002, a clinical isolate of vancomycin-resistant S. aureus (VRSA) (MIC, >32 u03bcg per milliliter) was identified.8 In this report, we describe our investigation of this infection, describe the mechanism of resistance, and discuss the clinical significance and public health implications of this finding.”, “author” : { “dropping-particle” : “”, “family” : “Chang”, “given” : “Soju”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Sievert”, “given” : “Dawn M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hageman”, “given” : “Jeffrey C”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Boulton”, “given” : “Matthew L”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tenover”, “given” : “Fred C”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Downes”, “given” : “Frances Pouch”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Shah”, “given” : “Sandip”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rudrik”, “given” : “James T”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pupp”, “given” : “Guy R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Brown”, “given” : “William J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Cardo”, “given” : “Denise”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Fridkin”, “given” : “Scott K”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The New England journal of medicine”, “id” : “ITEM-1”, “issue” : “14”, “issued” : { “date-parts” : “2003” }, “page” : “1342-1347”, “title” : “Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene.”, “type” : “article-journal”, “volume” : “348” }, “uris” : “http://www.mendeley.com/documents/?uuid=921bd0aa-08b6-434f-89f0-58b2fe1517e7” } , “mendeley” : { “formattedCitation” : “(S. Chang et al. 2003)”, “plainTextFormattedCitation” : “(S. Chang et al. 2003)”, “previouslyFormattedCitation” : “(S. Chang et al. 2003)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(S. Chang et al. 2003).

Vancomycin acts on cell-wall peptidoglycan by using binding to the carboxyl-terminal D-alanyl-D-alanine residues of peptidoglycan precursor and preventing PBPs from accessing to their ordinary substrate. About 20 layers of peptidoglycan have to penetrate by vancomycin to reach the cytoplasmic membrane in which the transglycosylation and transpeptidation reactions of PBPs take region. Vancomycin-resistance is associated with a thickening of the mobile wall caused by excessive activation of peptidoglycan synthesis within the VISA lines Mu50 and Mu3. The vancomycin molecules are trapped by way of high ranges of free D-alanyl-D-alanine residues because of the a good deal-reduced ranges of pass-linking ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0928-8244(03)00370-5”, “ISBN” : “0928-8244 (Print)\r0928-8244 (Linking)”, “ISSN” : “09288244”, “PMID” : “15040388”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) emerged in the early 1960s after the acquisition of the methicillin resistance gene mecA, which is carried by the staphylococcal cassette chromosome mec (SCCmec). MRSA seemed to have arisen by multiple introductions of SCCmec into successful methicillin-susceptible S. aureus (MSSA) lineages. MRSA is one of the most common agents of nosocomial infections worldwide increasing the cost and mortality compared to MSSA infections. Little by little, MRSA has acquired resistance to all antibiotics available in clinical practice, which complicates treatment. This situation was further aggravated by the recent reports of vanA-mediated vancomycin-resistant S. aureus. As a reaction to the emergence and spread of multidrug-resistant MRSA worldwide, international surveillance systems such as the CEM/NET initiative have been created. The characterization of over 3000 MRSA isolates from different regions of the world evidenced the existence of only a few epidemic clones spread worldwide, namely the Iberian, Brazilian, Hungarian, New York/Japan, Pediatric and EMRSA-16 clones. It was found that in surveillance or evolutionary studies strains should be characterized by a combination of different typing methods, namely pulsed-field gel electrophoresis, multi-locus sequence typing and SCCmec typing. In recent years, community-acquired MRSA (CA-MRSA) has become a growing public health concern. However, although many authors reported the emergence of CA-MRSA isolates, a standard definition has not been created and the prevalence of MRSA among persons without risk factors seems to remain very low. CA-MRSA has distinct properties compared to epidemic nosocomial MRSA clones and its origin is still unclear. Certain authors suggest there is MRSA transmission from the hospital setting to the community, namely transfer of nosocomial MRSA minor clones or sporadic isolates showing a high degree of similarity with CA-MRSA; others believe CA-MRSA strains represent new acquisitions of SCCmec DNA in susceptible backgrounds. Many questions concerning this extraordinarily versatile and threatening pathogen remain unanswered, needing future investigation. u00a9 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.”, “author” : { “dropping-particle” : “”, “family” : “Aires De Sousa”, “given” : “Marta”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lencastre”, “given” : “Hermu00ednia”, “non-dropping-particle” : “De”, “parse-names” : false, “suffix” : “” } , “container-title” : “FEMS Immunology and Medical Microbiology”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “2004” }, “page” : “101-111”, “title” : “Bridges from hospitals to the laboratory: Genetic portraits of methicillin-resistant Staphylococcus aureus clones”, “type” : “article”, “volume” : “40” }, “uris” : “http://www.mendeley.com/documents/?uuid=392a68fe-2d46-4ebc-803d-9711a35e43fa” } , “mendeley” : { “formattedCitation” : “(Aires De Sousa and De Lencastre 2004)”, “plainTextFormattedCitation” : “(Aires De Sousa and De Lencastre 2004)”, “previouslyFormattedCitation” : “(Aires De Sousa and De Lencastre 2004)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Aires De Sousa and De Lencastre 2004).

In comparison, complete vancomycin-resistance in S. Aureus (VRSA) is encoded by means of three determinants, particularly VanA, VanB and VanD, generally related to vancomycin- resistant enterococci (VRE). Resistance is brought about through the replacement of the native D-alanyl-D-alanine (D-Ala-D-Ala) residue of the cross-linking wall peptide with a D-alanyl-D-lactate (D-Ala-D-Lac) residue, which has a totally low affinity to glycopeptides. It is noteworthy that the VanA induces high level of resistance and additionally confers resistance to teicoplanin. The vanA gene cluster is carried on a large resistance plasmid ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1078/1438-4221-00185”, “ISBN” : “1438-4221 (Print)\r1438-4221 (Linking)”, “ISSN” : “1438-4221 (Print) 1438-4221 (Linking)”, “PMID” : “12139425”, “abstract” : “The introduction and increasing use of antibiotics for antibacterial therapy has initiated a rapid development and expansion of antibiotic resistance in microorganisms, particularly in human pathogens. Additionally, a shift to an increase in number and severity of Gram-positive infections has been observed the last decades. Common to these pathogens is their tendency to accumulate multiple resistances under antibiotic pressure and selection. Methicillin-resistant Staphylococcus aureus (MRSA), that have acquired multiresistance to all classes of antibiotics, have become a serious nosocomial problem. Recently, the emergence of the first MRSA with reduced vancomycin susceptibility evoked the specter of a totally resistant S. aureus. Problems with multiresistance expand also to penicillin-resistant Streptococcus pneumoniae that are partially or totally resistant to multiple antibiotics, and to vancomycin-resistant Enterococcus ssp., completely resistant to all commonly used antibiotics. The rapid development of resistance is due to mutational events and/or gene transfer and acquisition of resistance determinants, allowing strains to survive antibiotic treatment.”, “author” : { “dropping-particle” : “”, “family” : “Berger-Bachi”, “given” : “B”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Int J Med Microbiol”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2002” }, “page” : “27-35”, “title” : “Resistance mechanisms of gram-positive bacteria”, “type” : “article-journal”, “volume” : “292” }, “uris” : “http://www.mendeley.com/documents/?uuid=75b88aca-e4e4-4501-8c54-5ee8f9bb92a7” } , “mendeley” : { “formattedCitation” : “(Berger-Bachi 2002)”, “plainTextFormattedCitation” : “(Berger-Bachi 2002)”, “previouslyFormattedCitation” : “(Berger-Bachi 2002)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Berger-Bachi 2002).

Figure SEQ Figure * ARABIC 2- The principle mechanism of penicillin resistance to ?-lactamases.a) Induction of staphylococcal ?-lactamase synthesis in the presence of the ?-lactam antibiotic penicillin. I. The DNA-binding protein BlaI binds to the operator region, thus repressing RNA transcription from both blaZ and blaR1-blaI. In the absence of penicillin, ?-lactamase is expressed at low levels. II. Binding of penicillin to the transmembrane sensor-transducer BlaR1 stimulates BlaR1 autocatalytic activation. III–IV. Active BlaR1 either directly or indirectly (via a second protein, BlaR2) cleaves BlaI into inactive fragments, allowing transcription of both blaZ and blaR1-blaI to commence. V–VII. ?-Lactamase, the extracellular enzyme encoded by blaZ (V), hydrolyzes the ?-lactam ring of penicillin (VI), thereby rendering it inactive (VII). (b) Mechanism of S. aureus resistance to methicillin. Synthesis of PBP2a proceeds in a fashion similar to that described for ?-lactamase. Exposure of MecR1 to a ?-lactam antibiotic induces MecR1 synthesis. MecR1 inactivates MecI, allowing synthesis of PBP2a. MecI and BlaI have coregulatory effects on the expression of PBP2a and ?-lactamase ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1172/JCI200318535”, “ISBN” : “0021-9738 (Print)”, “ISSN” : “00219738”, “PMID” : “12727914”, “abstract” : “In the early 1970s, physicians were finally forced to abandon their belief that, given the vast array of effec- tive antimicrobial agents, virtually all bacterial infec- tions were treatable. Their optimism was shaken by the emergence of resistance to multiple antibiotics among such pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. The evolution of increasingly antimicrobial- resistant bacterial species stems from a multitude of factors that includes the widespread and sometimes inappropriate use of antimicrobials, the extensive use of these agents as growth enhancers in animal feed, and, with the increase in regional and international travel, the relative ease with which antimicrobial-resist- ant bacteria cross geographic barriers.”, “author” : { “dropping-particle” : “”, “family” : “Lowy”, “given” : “Franklin D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Clinical Investigation”, “id” : “ITEM-1”, “issue” : “9”, “issued” : { “date-parts” : “2003” }, “page” : “1265-1273”, “title” : “Antimicrobial resistance: The example of Staphylococcus aureus”, “type” : “article”, “volume” : “111” }, “uris” : “http://www.mendeley.com/documents/?uuid=30504972-a6aa-479c-9721-e431f8cc1a44” } , “mendeley” : { “formattedCitation” : “(Lowy 2003)”, “plainTextFormattedCitation” : “(Lowy 2003)”, “previouslyFormattedCitation” : “(Lowy 2003)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Lowy 2003).

Methicillin-resistant Staphylococcus aureus (MRSA):Emerging methicillin resistance:Methicillin was introduced in 1959 to deal with infections because of penicillin-resistant Staphylococcus aureus. In 1961 there were reviews from the United Kingdom of S. aureus isolates that had received resistance to methicillin (methicillin-resistant S. aureus, MRSA) ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1136/bmj.1.5219.124-a”, “ISBN” : “0959-8138”, “ISSN” : “00071447”, “PMID” : “13697147”, “abstract” : “300 Multiple ChoicesThis is a pdf-only article and there is no markup to show you.full-text.pdf”, “author” : { “dropping-particle” : “”, “family” : “Jevons”, “given” : “M. Patricia”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “British Medical Journal”, “id” : “ITEM-1”, “issue” : “5219”, “issued” : { “date-parts” : “1961” }, “page” : “124-125”, “title” : “u201cCelbeninu201d -resistant Staphylococci”, “type” : “article”, “volume” : “1” }, “uris” : “http://www.mendeley.com/documents/?uuid=69b2b4bc-c177-436d-9170-9738c4df9180”, “http://www.mendeley.com/documents/?uuid=0db83e79-3d27-41cd-8f96-68fa4eaabf64” } , “mendeley” : { “formattedCitation” : “(Jevons 1961)”, “plainTextFormattedCitation” : “(Jevons 1961)”, “previouslyFormattedCitation” : “(Jevons 1961)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Jevons 1961).

Penicillin was the effective drug of choice to treat several types infection, within 10 years after penicillin was introduced to be used in treating patients, it became non effectual of treating S. aureus infections due to acquisition of plasmid- encoded beta lactamase ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1126/science.99.2579.452”, “ISBN” : “0036-8075 (Print)\r0036-8075 (Linking)”, “ISSN” : “0036-8075”, “PMID” : “17798398”, “abstract” : “A highly potent penicillin inactivator has been extracted from 7 strains of Staph. aureus (coagulase positive), all of which were naturally penicillin resistant. No such inhibitor was present in extracts of 7 penicillin sensitive strains of Staph. aureus.”, “author” : { “dropping-particle” : “”, “family” : “Kirby”, “given” : “W M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Science (New York, N.Y.)”, “id” : “ITEM-1”, “issue” : “2579”, “issued” : { “date-parts” : “1944” }, “page” : “452-3”, “title” : “Extraction of a Highly Potent Pencinllin Inactivator from Pencillin Resistant Staphylococci”, “type” : “article-journal”, “volume” : “99” }, “uris” : “http://www.mendeley.com/documents/?uuid=fc3440f5-f352-4202-85b1-ce3b71e52c5a” } , “mendeley” : { “formattedCitation” : “(Kirby 1944)”, “plainTextFormattedCitation” : “(Kirby 1944)”, “previouslyFormattedCitation” : “(Kirby 1944)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Kirby 1944) Penicillin-resistant S. aureus turn into pandemic during late 1950s and early 1960s ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “ISBN” : “0025-729X; 0025-729X”, “ISSN” : “0025729X”, “PMID” : “13253118”, “author” : { “dropping-particle” : “”, “family” : “ROUNTREE”, “given” : “P. M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “FREEMAN”, “given” : “B. M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Medical journal of Australia”, “id” : “ITEM-1”, “issue” : “5”, “issued” : { “date-parts” : “1955” }, “page” : “157-161”, “title” : “Infections caused by a particular phage type of Staphylococcus aureus”, “type” : “article-journal”, “volume” : “42” }, “uris” : “http://www.mendeley.com/documents/?uuid=697184b7-dd51-47fc-8051-2452dd563796” } , “mendeley” : { “formattedCitation” : “(ROUNTREE and FREEMAN 1955)”, “plainTextFormattedCitation” : “(ROUNTREE and FREEMAN 1955)”, “previouslyFormattedCitation” : “(ROUNTREE and FREEMAN 1955)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(ROUNTREE and FREEMAN 1955). In 1961, MRSA was first reported and that was two years after the antibiotic was introduced to treat penicillin-resistant S. aureus.
Inside the UK, the number of MRSA infections remained restricted for numerous years. At the start of the 1971, MRSA represented 10% of all S. aureus isolates at the general health facility in Birmingham. Interestingly by way of the mid-1970s, the quantity of said MRSA instances declined to sincerely zero, and thought to be because of a combination using aminoglycoside antibiotics and higher infection manage methods ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “ISBN” : “1465-1645 (Print)”, “ISSN” : “1465-1645”, “PMID” : “15615149”, “abstract” : “This article examines trends in infection and mortality from methicillin-resistant Staphylococcus aureus (MRSA) over the period 1993 to 2002. Trends in the number of deaths where MRSA was mentioned on the death certificate were compared with national reporting of microbiologically-confirmed bacteraemia to the Health Protection Agency Communicable Disease Surveillance Centre (CDSC). Alongside national trends, patterns in the place of death were examined. Both the number of deaths and number of laboratory reports increased substantially over the period examined. MRSA mortality rates increased over 15-fold during the period 1993 to 2002. Reporting rates for bacteraemia increased 24-fold.”, “author” : { “dropping-particle” : “”, “family” : “Griffiths”, “given” : “Clare”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lamagni”, “given” : “Theresa L”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Crowcroft”, “given” : “Natasha S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Duckworth”, “given” : “Georgia”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rooney”, “given” : “Cleo”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Health statistics quarterly / Office for National Statistics”, “id” : “ITEM-1”, “issue” : “21”, “issued” : { “date-parts” : “2004” }, “page” : “15-22”, “title” : “Trends in MRSA in England and Wales: analysis of morbidity and mortality data for 1993-2002.”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=a4065d28-915b-4c01-9a33-bc315031a175” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1093/jac/dki266”, “ISBN” : “0305-7453 (Print)\r0305-7453 (Linking)”, “ISSN” : “03057453”, “PMID” : “16046464”, “abstract” : “Surveillance of bacteraemia caused by methicillin-resistant Staphylococcus aureus (MRSA) in the UK has involved collection of data from hospital microbiology laboratories via several mechanisms, including a voluntary reporting scheme that has been operational in England and Wales since 1989 and mandatory reporting schemes that have been running independently in England, Wales, Scotland and Northern Ireland since 2001. In addition, surveillance schemes involving panels of participating sentinel laboratories that submit isolates for centralized susceptibility testing, such as the Bacteraemia Resistance Surveillance Programme run by the BSAC, have also been established. Each of these data sources have particular advantages, but they also have their individual limitations, with the result that they each give an incomplete picture if considered in isolation. However, by pooling the findings from these different but complementary surveillance programmes, a much more comprehensive and credible picture of the problem posed by MRSA is produced. These schemes have shown both a dramatic rise in the total numbers of cases of S. aureus bacteraemia reported annually and an increase in the proportion of such cases that involve MRSA (from 2% in 1990 to >40% in the early 2000s), although the most recent data indicate a slight reversal of these trends. Characterization of isolates of MRSA shows a marked temporal relationship between the rise in MRSA bacteraemias and the emergence and spread of two strains of epidemic MRSA, EMRSA-15 and EMRSA-16. Surveillance and control of MRSA infection continue to be high profile and further developments to the mandatory surveillance system in England are likely in the near future.”, “author” : { “dropping-particle” : “”, “family” : “Johnson”, “given” : “Alan P.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pearson”, “given” : “Andrew”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Duckworth”, “given” : “Georgia”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Antimicrobial Chemotherapy”, “id” : “ITEM-2”, “issue” : “3”, “issued” : { “date-parts” : “2005” }, “page” : “455-462”, “title” : “Surveillance and epidemiology of MRSA bacteraemia in the UK”, “type” : “article”, “volume” : “56” }, “uris” : “http://www.mendeley.com/documents/?uuid=23b344e4-3167-4c3b-91d4-dc19d461ca20” }, { “id” : “ITEM-3”, “itemData” : { “DOI” : “10.1016/S0140-6736(06)68853-3”, “ISBN” : “1474-547X (Electronic)\n0140-6736 (Linking)”, “ISSN” : “01406736”, “PMID” : “16950365”, “abstract” : “Staphylococcus aureus is a gram-positive bacterium that colonises the skin and is present in the anterior nares in about 25-30% of healthy people.1Dependent on its intrinsic virulence or the ability of the host to contain its opportunistic behaviour, S aureus can cause a range of diseases in man. The bacterium readily acquires resistance against all classes of antibiotics by one of two distinct mechanisms: mutation of an existing bacterial gene or horizontal transfer of a resistance gene from another bacterium. Several mobile genetic elements carrying exogenous antibiotic resistance genes might mediate resistance acquisition.2Of all the resistance traits S aureus has acquired since the introduction of antimicrobial chemotherapy in the 1930s, meticillin resistance is clinically the most important, since a single genetic element confers resistance to the most commonly prescribed class of antimicrobials-the u03b2-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems. u00a9 2006 Elsevier Ltd. All rights reserved.”, “author” : { “dropping-particle” : “”, “family” : “Grundmann”, “given” : “Hajo”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Aires-de-Sousa”, “given” : “Marta”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Boyce”, “given” : “John”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tiemersma”, “given” : “Edine”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Lancet”, “id” : “ITEM-3”, “issue” : “9538”, “issued” : { “date-parts” : “2006” }, “page” : “874-885”, “title” : “Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat”, “type” : “article”, “volume” : “368” }, “uris” : “http://www.mendeley.com/documents/?uuid=d269620c-cda4-4040-91a7-f8df127a6846” } , “mendeley” : { “formattedCitation” : “(Griffiths et al. 2004; Grundmann et al. 2006; Alan P. Johnson, Pearson, and Duckworth 2005)”, “plainTextFormattedCitation” : “(Griffiths et al. 2004; Grundmann et al. 2006; Alan P. Johnson, Pearson, and Duckworth 2005)”, “previouslyFormattedCitation” : “(Griffiths et al. 2004; Grundmann et al. 2006; Alan P. Johnson, Pearson, and Duckworth 2005)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Griffiths et al. 2004; Grundmann et al. 2006; Alan P. Johnson, Pearson, and Duckworth 2005).

In 1982, an epidemic strain of multi-resistant MRSA reported in Australia, and the same strain was observed in London in connection with a health care facility outbreak. The staphylococcal reference laboratory of the UK Public Health Laboratory Service mounted a numerical prefix for epidemic MRSA strains and, based on this method, 16 epidemic strains have been identified England and Wales up to 1995. Though, most effective three epidemic traces, UK EMRSA-3, UK EMRSA-15 and UK EMRSA-16, were nonetheless being recorded inside the 1990s and EMRSA-15 and EMRSA-16 have been interactively greater energetic. In the meantime, six epidemic MRSA strains had been recorded in a few relevant Europe nations ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0140-6736(06)68853-3”, “ISBN” : “1474-547X (Electronic)\n0140-6736 (Linking)”, “ISSN” : “01406736”, “PMID” : “16950365”, “abstract” : “Staphylococcus aureus is a gram-positive bacterium that colonises the skin and is present in the anterior nares in about 25-30% of healthy people.1Dependent on its intrinsic virulence or the ability of the host to contain its opportunistic behaviour, S aureus can cause a range of diseases in man. The bacterium readily acquires resistance against all classes of antibiotics by one of two distinct mechanisms: mutation of an existing bacterial gene or horizontal transfer of a resistance gene from another bacterium. Several mobile genetic elements carrying exogenous antibiotic resistance genes might mediate resistance acquisition.2Of all the resistance traits S aureus has acquired since the introduction of antimicrobial chemotherapy in the 1930s, meticillin resistance is clinically the most important, since a single genetic element confers resistance to the most commonly prescribed class of antimicrobials-the u03b2-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems. u00a9 2006 Elsevier Ltd. All rights reserved.”, “author” : { “dropping-particle” : “”, “family” : “Grundmann”, “given” : “Hajo”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Aires-de-Sousa”, “given” : “Marta”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Boyce”, “given” : “John”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tiemersma”, “given” : “Edine”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Lancet”, “id” : “ITEM-1”, “issue” : “9538”, “issued” : { “date-parts” : “2006” }, “page” : “874-885”, “title” : “Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat”, “type” : “article”, “volume” : “368” }, “uris” : “http://www.mendeley.com/documents/?uuid=d269620c-cda4-4040-91a7-f8df127a6846” } , “mendeley” : { “formattedCitation” : “(Grundmann et al. 2006)”, “plainTextFormattedCitation” : “(Grundmann et al. 2006)”, “previouslyFormattedCitation” : “(Grundmann et al. 2006)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Grundmann et al. 2006).

Based on the Centers for Disease Control (CDC) and the National Nosocomial Infection Surveillance System (NNISS), the incidence of MRSA in US hospitals increased noticeably from 2.4% in 1975 to 29% in 1991 ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/jac/dkf009”, “ISBN” : “14602091”, “ISSN” : “0305-7453”, “PMID” : “12039892”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide. To investigate an association between antimicrobial use and MRSA, a case control study of 121 patients infected with MRSA compared with 123 patients infected with methicillin-susceptible S. aureus (MSSA) was carried out. Antimicrobial use was analysed by three different logistic regression models: all beta-lactam antibiotics, beta-lactam antibiotics grouped in classes and antimicrobial use in grammes. Patients infected with MRSA tended to have more co-morbidities, longer lengths of stay (LOS) and greater exposure to antibiotics than MSSA-infected patients. Multivariate analysis identified levofloxacin odds ratio (OR) 8.01, macrolides (OR 4.06), previous hospitalization (OR 1.95), enteral feedings (OR 2.55), surgery (OR 2.24) and LOS before culture (OR 1.03) as independently associated with MRSA infection. All models were concordant with the exception of macrolides, which were not significant based on the number of grammes administered. There were no significant differences in the types of infection or the attributed mortality in either group. MRSA-infected patients had a significantly longer LOS before infection 18.8 +/- 18.2 compared with 8.4 +/- 6.9 (P < 0.001) and a significantly longer post-diagnosis LOS 27.8 +/- 32.9 compared with 18.6 +/- 21 (P = 0.01) than MSSA-infected patients.”, “author” : { “dropping-particle” : “”, “family” : “Graffunder”, “given” : “Eileen M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Venezia”, “given” : “Richard a”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Journal of antimicrobial chemotherapy”, “id” : “ITEM-1”, “issue” : “6”, “issued” : { “date-parts” : “2002” }, “page” : “999-1005”, “title” : “Risk factors associated with nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection including previous use of antimicrobials.”, “type” : “article-journal”, “volume” : “49” }, “uris” : “http://www.mendeley.com/documents/?uuid=c6408995-e729-4bc0-9f34-cd655e7da0e1” } , “mendeley” : { “formattedCitation” : “(Graffunder and Venezia 2002)”, “plainTextFormattedCitation” : “(Graffunder and Venezia 2002)”, “previouslyFormattedCitation” : “(Graffunder and Venezia 2002)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Graffunder and Venezia 2002). In other hand, In the UK MRSA bacteraemias remained at 3% until 1992, then increased noticeably to reach 43% by 2002. Since then, the rate of isolation of MRSA strains has increased significantly every year worldwide ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0140-6736(06)68853-3”, “ISBN” : “1474-547X (Electronic)\n0140-6736 (Linking)”, “ISSN” : “01406736”, “PMID” : “16950365”, “abstract” : “Staphylococcus aureus is a gram-positive bacterium that colonises the skin and is present in the anterior nares in about 25-30% of healthy people.1Dependent on its intrinsic virulence or the ability of the host to contain its opportunistic behaviour, S aureus can cause a range of diseases in man. The bacterium readily acquires resistance against all classes of antibiotics by one of two distinct mechanisms: mutation of an existing bacterial gene or horizontal transfer of a resistance gene from another bacterium. Several mobile genetic elements carrying exogenous antibiotic resistance genes might mediate resistance acquisition.2Of all the resistance traits S aureus has acquired since the introduction of antimicrobial chemotherapy in the 1930s, meticillin resistance is clinically the most important, since a single genetic element confers resistance to the most commonly prescribed class of antimicrobials-the u03b2-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems. u00a9 2006 Elsevier Ltd. All rights reserved.”, “author” : { “dropping-particle” : “”, “family” : “Grundmann”, “given” : “Hajo”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Aires-de-Sousa”, “given” : “Marta”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Boyce”, “given” : “John”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tiemersma”, “given” : “Edine”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Lancet”, “id” : “ITEM-1”, “issue” : “9538”, “issued” : { “date-parts” : “2006” }, “page” : “874-885”, “title” : “Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat”, “type” : “article”, “volume” : “368” }, “uris” : “http://www.mendeley.com/documents/?uuid=d269620c-cda4-4040-91a7-f8df127a6846” } , “mendeley” : { “formattedCitation” : “(Grundmann et al. 2006)”, “plainTextFormattedCitation” : “(Grundmann et al. 2006)”, “previouslyFormattedCitation” : “(Grundmann et al. 2006)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Grundmann et al. 2006).

MRSA isolates had been soon recovered from different European nations, and later from Japan, Australia, and America ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “ISSN” : “0891-3668 (Print)”, “PMID” : “11144377”, “abstract” : “BACKGROUND: The prevalence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections increased at the University of Chicago Children’s Hospital (UCCH) from 10 per 100,000 admissions from 1988 to 1990 to 259 per 100,000 admissions from 1993 to 1995. Because this increase may have represented a one time occurrence or a limited disease outbreak, we updated our previous observations at UCCH in 1998 and 1999 to see whether this trend had continued. DESIGN: Prospective observational study. RESULTS: Twenty-three hospitalized children had an MRSA isolate during the 1-year study period. Ten were community-acquired, equally distributed between children with predisposing risk factors and those without. The overall prevalence of community-acquired MRSA was 208 per 100,000 admissions. Seven of the 10 community-acquired MRSA isolates were susceptible to clindamycin. Skin and soft tissue infections predominated among the children with a community-acquired MRSA isolate. Pulsed field gel electrophoresis of the 10 community-acquired MRSA isolates revealed 8 distinct patterns; these data suggest that multiple clones were circulating at UCCH. CONCLUSION: MRSA are no longer confined to children with established risk factors. The prevalence of community-acquired MRSA among children without identified risk factors is high in our institution.”, “author” : { “dropping-particle” : “”, “family” : “Hussain”, “given” : “F M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Boyle-Vavra”, “given” : “S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Bethel”, “given” : “C D”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Daum”, “given” : “R S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Pediatric infectious disease journal”, “id” : “ITEM-1”, “issue” : “12”, “issued” : { “date-parts” : “2000” }, “page” : “1163-1166”, “title” : “Current trends in community-acquired methicillin-resistant Staphylococcus aureus at a tertiary care pediatric facility.”, “type” : “article-journal”, “volume” : “19” }, “uris” : “http://www.mendeley.com/documents/?uuid=9dac8100-898d-4502-9267-1a5f6e9093e3”, “http://www.mendeley.com/documents/?uuid=4cf74b6b-36a9-48cc-b1a0-ecabf661fa7c” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1001/jama.282.12.1123-JWR0922-2-1”, “ISBN” : “0098-7484 (Print)\r0098-7484 (Linking)”, “ISSN” : “00987484”, “PMID” : “10501104”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging community-acquired pathogen among patients without established risk factors for MRSA infection (e.g., recent hospitalization, recent surgery, residence in a long-term-care facility LTCF, or injecting-drug use IDU) (1). Since 1996, the Minnesota Department of Health (MDH) and the Indian Health Service (IHS) have investigated cases of community-acquired MRSA infection in patients without established risk factors. This report describes four fatal cases among children with community-acquired MRSA; the MRSA strains isolated from these patients appear to be different from typical nosocomial MRSA strains in antimicrobial susceptibility patterns and pulsed-field gel electrophoresis (PFGE) characteristics.”, “author” : { “dropping-particle” : “”, “family” : “Prevention”, “given” : “Centers for Disease Control and”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “JAMA”, “id” : “ITEM-2”, “issue” : “12”, “issued” : { “date-parts” : “1999” }, “page” : “1123”, “title” : “Four Pediatric Deaths From Community-Acquired Methicillin-Resistant Staphylococcus aureusu2014Minnesota and North Dakota, 1997-1999”, “type” : “article-journal”, “volume” : “282” }, “uris” : “http://www.mendeley.com/documents/?uuid=b143ffa1-c968-465c-a8ae-712787c0088a”, “http://www.mendeley.com/documents/?uuid=111da874-0e76-4fd7-a4b5-04b3d22fa03a” } , “mendeley” : { “formattedCitation” : “(Hussain et al. 2000; Prevention 1999)”, “plainTextFormattedCitation” : “(Hussain et al. 2000; Prevention 1999)”, “previouslyFormattedCitation” : “(Hussain et al. 2000; Prevention 1999)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Hussain et al. 2000; Prevention 1999). Furthermore, this superbug is a crucial issue in hospitals globally and is more and more recovered from nursing homes and the network MRSA has been though as the major hospital pathogen. Recent study showed that the CA-MRSA is now taking over control through the community and health care facilities, and did cause an outbreak among athletes, children’s, seniors and even healthy peoples ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1086/528716”, “ISBN” : “1537-6591 (Electronic)\r1058-4838 (Linking)”, “ISSN” : “1058-4838”, “PMID” : “18266611”, “abstract” : “BACKGROUND: Recent studies have suggested that community-associated methicillin-resistant Staphylococcus aureus (MRSA) infection is encroaching on health care settings. We describe the epidemiology of hospital-onset community-associated MRSA bloodstream infections using phenotypic and genotypic analysis. METHODS: Using an update of an established rule derived from antibiotic susceptibilities, we inferred genotypes (i.e., community CG or hospital HG) for 208 MRSA isolates from hospital-onset (;72 h after hospital admission) bloodstream infections during 2000-2006. We compared demographic characteristics, risk factors, and outcomes of patients infected with CG or HG strains. RESULTS: Total hospital-onset MRSA bloodstream infection incidence density rates for the periods January 2000-June 2003 and July 2003-December 2006 (0.215 cases per 1000 patient-days and 0.207 cases per 1000 patient-days, respectively) were stable (risk ratio, 1.0; 95% confidence interval, 0.7-1.3; P = .79, period 2 vs. period 1). However, the risk that these bloodstream infections were due to CG strains doubled (risk ratio, 1.9; 95% confidence interval, 1.2-3.1; P = .01), whereas the risk due to HG strains decreased (risk ratio, 0.7; 95% confidence interval, 0.46-0.93; P = .02). After adjustment for comorbidities in multivariate analysis, no significant risk factors for or outcomes of infections due to CG versus HG strains were detected. Patients infected with HG strains showed a trend toward later day of acquisition of a positive blood culture, and those infected with CG strains showed trend toward greater risk of intensive care unit admission. CONCLUSION: Although total hospital-onset MRSA bloodstream infection rates were relatively stable during 2000-2006, CG strains were responsible for an increasing proportion of cases (from 24% to 49%), suggesting replacement of traditional hospital-associated strains. For most risk factors and outcomes, patients infected with CG and HG strains were similar, suggesting that, thus far, CG strains are behaving like their traditional hospital-associated counterparts.”, “author” : { “dropping-particle” : “”, “family” : “Popovich”, “given” : “K. J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Weinstein”, “given” : “R. A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hota”, “given” : “B.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Infectious Diseases”, “id” : “ITEM-1”, “issue” : “6”, “issued” : { “date-parts” : “2008” }, “page” : “787-794”, “title” : “Are Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) Strains Replacing Traditional Nosocomial MRSA Strains?”, “type” : “article-journal”, “volume” : “46” }, “uris” : “http://www.mendeley.com/documents/?uuid=ee74f323-a730-42d6-86aa-9380ad6ef79f” } , “mendeley” : { “formattedCitation” : “(Popovich, Weinstein, and Hota 2008)”, “plainTextFormattedCitation” : “(Popovich, Weinstein, and Hota 2008)”, “previouslyFormattedCitation” : “(Popovich, Weinstein, and Hota 2008)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Popovich, Weinstein, and Hota 2008).

Table SEQ Table * ARABIC 1: The sequenced genomes of S.aureusMechanism of Methicillin-resistance:Methicillin-resistance in staphylococci is due to the acquisition of a large mobile DNA element (20 to 100kb in size), the so-called “Staphylococcal cassette chromosome mec” (SCCmec) ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1146/annurev-biochem-060614-034516”, “ISBN” : “1545-4509 (Electronic) 0066-4154 (Linking)”, “ISSN” : “0066-4154”, “PMID” : “26034890”, “abstract” : “Staphylococcus aureus is a major human and veterinary pathogen worldwide. Methicillin-resistant S. aureus (MRSA) poses a significant and enduring problem to the treatment of infection by such strains. Resistance is usu-ally conferred by the acquisition of a nonnative gene encoding a penicillin-binding protein (PBP2a), with significantly lower affinity for u03b2-lactams. This resistance allows cell-wall biosynthesis, the target of u03b2-lactams, to continue even in the presence of typically inhibitory concentrations of antibiotic. PBP2a is encoded by the mecA gene, which is carried on a distinct mobile ge-netic element (SCCmec), the expression of which is controlled through a pro-teolytic signal transduction pathway comprising a sensor protein (MecR1) and a repressor (MecI). Many of the molecular and biochemical mechanisms underlying methicillin resistance in S. aureus have been elucidated, including regulatory events and the structure of key proteins. Here we review recent advances in this area.”, “author” : { “dropping-particle” : “”, “family” : “Peacock”, “given” : “Sharon J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Paterson”, “given” : “Gavin K”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Annual Review of Biochemistry”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2015” }, “page” : “577-601”, “title” : “Mechanisms of Methicillin Resistance in Staphylococcus aureus”, “type” : “article-journal”, “volume” : “84” }, “uris” : “http://www.mendeley.com/documents/?uuid=cc93b1e9-0a8d-46ed-9368-2613e440887b” } , “mendeley” : { “formattedCitation” : “(Peacock and Paterson 2015)”, “plainTextFormattedCitation” : “(Peacock and Paterson 2015)”, “previouslyFormattedCitation” : “(Peacock and Paterson 2015)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Peacock and Paterson 2015). Presently, eight SCCmec types (I to VIII) have been described in details (see Section 1.3).

The mechanism of action of ?-lactam antibiotics to destroy bacteria are by inhibiting bacterial cell wall synthesis. The antibiotic, an equivalent of D-alanyl-D-alanine, covalently attaches to PBPs. These membrane-anchored proteins catalyze one or more of three reactions (transpeptidase, endopeptidase and carboxypeptidase) which involved in cell wall synthesis. MRSA produces a modified PBP2a that can complete cell wall synthesis when the transpeptidation activities of the native PBPs are inactivated by the antibiotic ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1146/annurev-biochem-060614-034516”, “ISBN” : “1545-4509 (Electronic) 0066-4154 (Linking)”, “ISSN” : “0066-4154”, “PMID” : “26034890”, “abstract” : “Staphylococcus aureus is a major human and veterinary pathogen worldwide. Methicillin-resistant S. aureus (MRSA) poses a significant and enduring problem to the treatment of infection by such strains. Resistance is usu-ally conferred by the acquisition of a nonnative gene encoding a penicillin-binding protein (PBP2a), with significantly lower affinity for u03b2-lactams. This resistance allows cell-wall biosynthesis, the target of u03b2-lactams, to continue even in the presence of typically inhibitory concentrations of antibiotic. PBP2a is encoded by the mecA gene, which is carried on a distinct mobile ge-netic element (SCCmec), the expression of which is controlled through a pro-teolytic signal transduction pathway comprising a sensor protein (MecR1) and a repressor (MecI). Many of the molecular and biochemical mechanisms underlying methicillin resistance in S. aureus have been elucidated, including regulatory events and the structure of key proteins. Here we review recent advances in this area.”, “author” : { “dropping-particle” : “”, “family” : “Peacock”, “given” : “Sharon J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Paterson”, “given” : “Gavin K”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Annual Review of Biochemistry”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2015” }, “page” : “577-601”, “title” : “Mechanisms of Methicillin Resistance in Staphylococcus aureus”, “type” : “article-journal”, “volume” : “84” }, “uris” : “http://www.mendeley.com/documents/?uuid=cc93b1e9-0a8d-46ed-9368-2613e440887b” } , “mendeley” : { “formattedCitation” : “(Peacock and Paterson 2015)”, “plainTextFormattedCitation” : “(Peacock and Paterson 2015)”, “previouslyFormattedCitation” : “(Peacock and Paterson 2015)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Peacock and Paterson 2015). Resistance is because of the fact that PBP2a has low affinity to ?-lactams antibiotics. The expression of the mecA gene is controlled via the products of the mecRI and mecI genes. MecRI synthesis is induced upon exposure to ?- lactam antibiotics. As an end result, the MecI repressor is inactivated and PBP2a produced (Figure 1.2; Lowy, 2003).
Staphylococcal cassette chromosome mec (SCCmec) elements:The emergence of MRSA is the result of the gaining of a mecA gene by the chromosome of an MSSA strain. This mecA gene is methicillin-resistance conferred by a large (21- 67 kb) mobile genetic element called the staphylococcal cassette chromosome mec (SCCmec) element ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/978-1-62703-664-1_2”, “ISBN” : “9781627036641”, “ISSN” : “1940-6029”, “PMID” : “24085688”, “abstract” : “Over the past decade, the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the landscape of S. aureus infections around the globe. Initially recognized for its ability to cause disease in young and healthy individuals without healthcare exposures as well as for its distinct genotype and phenotype, this original description no longer fully encompasses the diversity of CA-MRSA as it continues to expand its niche. Using four case studies, we highlight a wide range of the clinical presentations and challenges of CA-MRSA. Based on these cases we further explore the globally polygenetic background of CA-MRSA with a special emphasis on generally less characterized populations.”, “author” : { “dropping-particle” : “”, “family” : “Sowash”, “given” : “Madeleine G”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Uhlemann”, “given” : “Anne-Catrin”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Methods in molecular biology (Clifton, N.J.)”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2014” }, “page” : “25-69”, “title” : “Community-associated methicillin-resistant Staphylococcus aureus case studies.”, “type” : “article-journal”, “volume” : “1085” }, “uris” : “http://www.mendeley.com/documents/?uuid=8249c17d-cae7-4e5f-9c26-5bd672156375” } , “mendeley” : { “formattedCitation” : “(Sowash and Uhlemann 2014)”, “plainTextFormattedCitation” : “(Sowash and Uhlemann 2014)”, “previouslyFormattedCitation” : “(Sowash and Uhlemann 2014)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Sowash and Uhlemann 2014).

The source and origin of SCCmec is unknown. However, there is confirmation that SCCmec can be transferred horizontally between staphylococcal species, and coagulase-negative staphylococci (CNS) are a potential source for SCCmec ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1111/j.1574-695X.2005.00009.x”, “ISBN” : “1574-695X”, “ISSN” : “09288244”, “PMID” : “16420592”, “abstract” : “Staphylococcal cassette chromosome (SCC) elements are, so far, the only vectors described for the mecA gene encoding methicillin resistance in staphylococci. SCCmec elements are classified according to the type of recombinase they carry and their general genetic composition. SCCmec types I-V have been described, and SCC elements lacking mecA have also been reported. In this review, we summarize the current knowledge about SCC structure and distribution, including genetic variants and rudiments of the elements. Its origin is still unknown, but one assumes that staphylococcal cassette chromosome is transferred between staphylococci, and mecA-positive coagulase-negative staphylococci may be a potential reservoir for these elements. Staphylococcal genomes seem to change continuously as genetic elements move in and out, but no mechanism of transfer has been found responsible for moving SCC elements between different staphylococcal species. Observations suggesting de novo production of methicillin-resistant staphylococci and horizontal gene transfer of SCCmec will be discussed.”, “author” : { “dropping-particle” : “”, “family” : “Hanssen”, “given” : “Anne Merethe”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ericson Sollid”, “given” : “Johanna U.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “FEMS Immunology and Medical Microbiology”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “8-20”, “title” : “SCCmec in staphylococci: Genes on the move”, “type” : “article”, “volume” : “46” }, “uris” : “http://www.mendeley.com/documents/?uuid=fd47f350-9c08-45ed-9fd1-53d0c0062a7a” } , “mendeley” : { “formattedCitation” : “(Hanssen and Ericson Sollid 2006)”, “plainTextFormattedCitation” : “(Hanssen and Ericson Sollid 2006)”, “previouslyFormattedCitation” : “(Hanssen and Ericson Sollid 2006)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Hanssen and Ericson Sollid 2006).

Conferring to their genetic structure and contents, SCCmec elements are classified into several types and subtypes. Almost all SCCmec types shared common characteristics: (1) the elements carry the mec gene complex; (2) They have a cassette chromosome recombinase (ccr) gene complex; (3) SCCmec elements participate at the same site into chromosome; (4) They are lined by incomplete inverted and direct repeats sequences that contain integration site sequence (ISS) and located at the integration site of chromosome; those repeat sequences are identified by ccr recombinases during the excision and integration of SCCmec ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1111/j.1574-695X.2005.00009.x”, “ISBN” : “1574-695X”, “ISSN” : “09288244”, “PMID” : “16420592”, “abstract” : “Staphylococcal cassette chromosome (SCC) elements are, so far, the only vectors described for the mecA gene encoding methicillin resistance in staphylococci. SCCmec elements are classified according to the type of recombinase they carry and their general genetic composition. SCCmec types I-V have been described, and SCC elements lacking mecA have also been reported. In this review, we summarize the current knowledge about SCC structure and distribution, including genetic variants and rudiments of the elements. Its origin is still unknown, but one assumes that staphylococcal cassette chromosome is transferred between staphylococci, and mecA-positive coagulase-negative staphylococci may be a potential reservoir for these elements. Staphylococcal genomes seem to change continuously as genetic elements move in and out, but no mechanism of transfer has been found responsible for moving SCC elements between different staphylococcal species. Observations suggesting de novo production of methicillin-resistant staphylococci and horizontal gene transfer of SCCmec will be discussed.”, “author” : { “dropping-particle” : “”, “family” : “Hanssen”, “given” : “Anne Merethe”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ericson Sollid”, “given” : “Johanna U.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “FEMS Immunology and Medical Microbiology”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “8-20”, “title” : “SCCmec in staphylococci: Genes on the move”, “type” : “article”, “volume” : “46” }, “uris” : “http://www.mendeley.com/documents/?uuid=fd47f350-9c08-45ed-9fd1-53d0c0062a7a” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1007/978-1-62703-664-1_8”, “ISBN” : “9781627036634”, “ISSN” : “10643745”, “PMID” : “24085694”, “abstract” : “Methicillin-susceptible S. aureus (MSSA) changes to methicillin-resistant S. aureus upon the acquisition of Staphylococcal Cassette Chromosome mec (SCCmec), a genomic island that encodes methicillin resistance. All SCCmec elements reported to date share four common characteristics: (1) carrying the mec gene complex (mec); (2) carrying the ccr gene complex (ccr); (3) being flanked by characteristic nucleotide sequences, inverted repeats, and direct repeats, at both ends; and (4) being integrated at the integration site sequence (ISS) for SCC, which is located at the 3′-end of orfX or at the extremity of the SCC element. SCCmec elements in S. aureus are classified into different types based on the combination of mec and ccr, which share variations, five classes in mec and eight in ccr. To date, at least 11 types of SCCmec elements have been identified. Regions other than mec and ccr within the SCCmec element are designated as “joining regions” (J-regions), which are classified into three subgroups, J1-3. Many J-region variants have been identified among the SCCmec elements of types I-V. We herein describe PCR methods to type SCCmec elements by first identifying the mec and ccr type, and then identifying genes in the J-regions”, “author” : { “dropping-particle” : “”, “family” : “Ito”, “given” : “Teruyo”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kuwahara-Arai”, “given” : “Kyoko”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Katayama”, “given” : “Yuki”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Uehara”, “given” : “Yuki”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Han”, “given” : “Xiao”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kondo”, “given” : “Yoko”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hiramatsu”, “given” : “Keiichi”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Methods in Molecular Biology”, “id” : “ITEM-2”, “issued” : { “date-parts” : “2014” }, “page” : “131-148”, “title” : “Staphylococcal cassette chromosome mec (SCCmec) analysis of MRSA”, “type” : “article-journal”, “volume” : “1085” }, “uris” : “http://www.mendeley.com/documents/?uuid=e6049326-5ea1-469d-aba3-5e0ec60715ff” } , “mendeley” : { “formattedCitation” : “(Hanssen and Ericson Sollid 2006; Teruyo Ito et al. 2014)”, “plainTextFormattedCitation” : “(Hanssen and Ericson Sollid 2006; Teruyo Ito et al. 2014)”, “previouslyFormattedCitation” : “(Hanssen and Ericson Sollid 2006; Teruyo Ito et al. 2014)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Hanssen and Ericson Sollid 2006; Teruyo Ito et al. 2014).

SCCmec elements are currently classified into various types and subtypes based on a combination of the class of the mec gene complex and the allotype of the ccr gene complex. In SCCmec of S. aureus, three classes of the mec gene complex have been described: class A, class B and class C1/C2 ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1007/978-1-62703-664-1_8”, “ISBN” : “9781627036634”, “ISSN” : “10643745”, “PMID” : “24085694”, “abstract” : “Methicillin-susceptible S. aureus (MSSA) changes to methicillin-resistant S. aureus upon the acquisition of Staphylococcal Cassette Chromosome mec (SCCmec), a genomic island that encodes methicillin resistance. All SCCmec elements reported to date share four common characteristics: (1) carrying the mec gene complex (mec); (2) carrying the ccr gene complex (ccr); (3) being flanked by characteristic nucleotide sequences, inverted repeats, and direct repeats, at both ends; and (4) being integrated at the integration site sequence (ISS) for SCC, which is located at the 3′-end of orfX or at the extremity of the SCC element. SCCmec elements in S. aureus are classified into different types based on the combination of mec and ccr, which share variations, five classes in mec and eight in ccr. To date, at least 11 types of SCCmec elements have been identified. Regions other than mec and ccr within the SCCmec element are designated as “joining regions” (J-regions), which are classified into three subgroups, J1-3. Many J-region variants have been identified among the SCCmec elements of types I-V. We herein describe PCR methods to type SCCmec elements by first identifying the mec and ccr type, and then identifying genes in the J-regions”, “author” : { “dropping-particle” : “”, “family” : “Ito”, “given” : “Teruyo”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kuwahara-Arai”, “given” : “Kyoko”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Katayama”, “given” : “Yuki”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Uehara”, “given” : “Yuki”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Han”, “given” : “Xiao”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kondo”, “given” : “Yoko”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hiramatsu”, “given” : “Keiichi”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Methods in Molecular Biology”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2014” }, “page” : “131-148”, “title” : “Staphylococcal cassette chromosome mec (SCCmec) analysis of MRSA”, “type” : “article-journal”, “volume” : “1085” }, “uris” : “http://www.mendeley.com/documents/?uuid=e6049326-5ea1-469d-aba3-5e0ec60715ff” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1111/j.1574-695X.2005.00009.x”, “ISBN” : “1574-695X”, “ISSN” : “09288244”, “PMID” : “16420592”, “abstract” : “Staphylococcal cassette chromosome (SCC) elements are, so far, the only vectors described for the mecA gene encoding methicillin resistance in staphylococci. SCCmec elements are classified according to the type of recombinase they carry and their general genetic composition. SCCmec types I-V have been described, and SCC elements lacking mecA have also been reported. In this review, we summarize the current knowledge about SCC structure and distribution, including genetic variants and rudiments of the elements. Its origin is still unknown, but one assumes that staphylococcal cassette chromosome is transferred between staphylococci, and mecA-positive coagulase-negative staphylococci may be a potential reservoir for these elements. Staphylococcal genomes seem to change continuously as genetic elements move in and out, but no mechanism of transfer has been found responsible for moving SCC elements between different staphylococcal species. Observations suggesting de novo production of methicillin-resistant staphylococci and horizontal gene transfer of SCCmec will be discussed.”, “author” : { “dropping-particle” : “”, “family” : “Hanssen”, “given” : “Anne Merethe”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ericson Sollid”, “given” : “Johanna U.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “FEMS Immunology and Medical Microbiology”, “id” : “ITEM-2”, “issue” : “1”, “issued” : { “date-parts” : “2006” }, “page” : “8-20”, “title” : “SCCmec in staphylococci: Genes on the move”, “type” : “article”, “volume” : “46” }, “uris” : “http://www.mendeley.com/documents/?uuid=fd47f350-9c08-45ed-9fd1-53d0c0062a7a” } , “mendeley” : { “formattedCitation” : “(Hanssen and Ericson Sollid 2006; Teruyo Ito et al. 2014)”, “plainTextFormattedCitation” : “(Hanssen and Ericson Sollid 2006; Teruyo Ito et al. 2014)”, “previouslyFormattedCitation” : “(Hanssen and Ericson Sollid 2006; Teruyo Ito et al. 2014)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Hanssen and Ericson Sollid 2006; Teruyo Ito et al. 2014). Moreover, an essential component of SCCmec is the ccr gene complex. Two genes (ccrA and ccrB) with four allotypes have been identified. A summary of the classification of ccr genes is showed in Table.1.2.

Epidemiology of MRSA in hospital:MRSA has considered as a major nosocomial pathogen and its prevalence continues to increase globally. In fact, morbidity and mortality rates among hospital patients has increased due to MRSA infections. According to the National Nosocomial Infections Surveillance (NNIS) approximately 80,000 patients per year suffer from MRSA infections ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0928-8244(03)00370-5”, “ISBN” : “0928-8244 (Print)\r0928-8244 (Linking)”, “ISSN” : “09288244”, “PMID” : “15040388”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) emerged in the early 1960s after the acquisition of the methicillin resistance gene mecA, which is carried by the staphylococcal cassette chromosome mec (SCCmec). MRSA seemed to have arisen by multiple introductions of SCCmec into successful methicillin-susceptible S. aureus (MSSA) lineages. MRSA is one of the most common agents of nosocomial infections worldwide increasing the cost and mortality compared to MSSA infections. Little by little, MRSA has acquired resistance to all antibiotics available in clinical practice, which complicates treatment. This situation was further aggravated by the recent reports of vanA-mediated vancomycin-resistant S. aureus. As a reaction to the emergence and spread of multidrug-resistant MRSA worldwide, international surveillance systems such as the CEM/NET initiative have been created. The characterization of over 3000 MRSA isolates from different regions of the world evidenced the existence of only a few epidemic clones spread worldwide, namely the Iberian, Brazilian, Hungarian, New York/Japan, Pediatric and EMRSA-16 clones. It was found that in surveillance or evolutionary studies strains should be characterized by a combination of different typing methods, namely pulsed-field gel electrophoresis, multi-locus sequence typing and SCCmec typing. In recent years, community-acquired MRSA (CA-MRSA) has become a growing public health concern. However, although many authors reported the emergence of CA-MRSA isolates, a standard definition has not been created and the prevalence of MRSA among persons without risk factors seems to remain very low. CA-MRSA has distinct properties compared to epidemic nosocomial MRSA clones and its origin is still unclear. Certain authors suggest there is MRSA transmission from the hospital setting to the community, namely transfer of nosocomial MRSA minor clones or sporadic isolates showing a high degree of similarity with CA-MRSA; others believe CA-MRSA strains represent new acquisitions of SCCmec DNA in susceptible backgrounds. Many questions concerning this extraordinarily versatile and threatening pathogen remain unanswered, needing future investigation. u00a9 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.”, “author” : { “dropping-particle” : “”, “family” : “Aires De Sousa”, “given” : “Marta”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lencastre”, “given” : “Hermu00ednia”, “non-dropping-particle” : “De”, “parse-names” : false, “suffix” : “” } , “container-title” : “FEMS Immunology and Medical Microbiology”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “2004” }, “page” : “101-111”, “title” : “Bridges from hospitals to the laboratory: Genetic portraits of methicillin-resistant Staphylococcus aureus clones”, “type” : “article”, “volume” : “40” }, “uris” : “http://www.mendeley.com/documents/?uuid=392a68fe-2d46-4ebc-803d-9711a35e43fa” } , “mendeley” : { “formattedCitation” : “(Aires De Sousa and De Lencastre 2004)”, “plainTextFormattedCitation” : “(Aires De Sousa and De Lencastre 2004)”, “previouslyFormattedCitation” : “(Aires De Sousa and De Lencastre 2004)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Aires De Sousa and De Lencastre 2004). Furthermore, hospital- acquired strains are usually defined as multi-drug resistant (MDR) MRSA because of their resistance to several classes of antibiotics such as ?-lactam, chloramphenicol, erythromycin, streptomycin and tetracycline antibiotics. Consequently, MRSA infections are difficult and costly to treat. Previous research have found out that the mortality rate associated with MRSA bacteremia is much greater than that related to MSSA bacteremia ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1086/345476”, “ISBN” : “1537-6591 (Electronic)\n1058-4838 (Linking)”, “ISSN” : “1537-6591”, “PMID” : “12491202”, “abstract” : “A meta-analysis was performed to summarize the impact of methicillin-resistance on mortality in Staphylococcus aureus bacteremia. A search of the MEDLINE database for studies published during the period of 1 January 1980 through 31 December 2000 and a bibliographic review identified English-language studies of S. aureus bacteremia. Studies were included if they contained the numbers of and mortality rates for patients with methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) bacteremia. Data were extracted on demographic characteristics of the patients, adjustment for severity and comorbid illness, source of bacteremia, and crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for in-hospital mortality. When the results were pooled with a random-effects model, a significant increase in mortality associated with MRSA bacteremia was evident (OR, 1.93; 95% CI, 1.54-2.42; P;.001); significant heterogeneity was present. We explored the reasons for heterogeneity by means of subgroup analyses. MRSA bacteremia is associated with significantly higher mortality rate than is MSSA bacteremia.”, “author” : { “dropping-particle” : “”, “family” : “Cosgrove”, “given” : “Sara E”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Sakoulas”, “given” : “George”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Perencevich”, “given” : “Eli N”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Schwaber”, “given” : “Mitchell J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Karchmer”, “given” : “Adolf W”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Carmeli”, “given” : “Yehuda”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical infectious diseases : an official publication of the Infectious Diseases Society of America”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2003” }, “page” : “53-9”, “title” : “Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis.”, “type” : “article-journal”, “volume” : “36” }, “uris” : “http://www.mendeley.com/documents/?uuid=8e3d5bda-56f8-45ca-acef-504818a23a94” } , “mendeley” : { “formattedCitation” : “(Cosgrove et al. 2003)”, “plainTextFormattedCitation” : “(Cosgrove et al. 2003)”, “previouslyFormattedCitation” : “(Cosgrove et al. 2003)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Cosgrove et al. 2003).

According to NNIS, about 51.3% of S. aureus isolates from the patients in intensive care units (ICUs) were methicillin-resistant between 1998 and 2002 in the USA ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1067/mic.2002.130032”, “ISBN” : “0196-6553 (Print)\r0196-6553 (Linking)”, “ISSN” : “01966553”, “PMID” : “15573054”, “abstract” : “This report is a summ ary of the data collected and reported by hospitals partic ipating in the National Nosoco mial Infectio ns Surveillance (NNIS) System from Januar y 1992 through June 2004 and updates pre viously published data. 1-4 The NNIS System w as established in 1970 when selected hospitals in t he United States routinely began reporting their nosoco mial infecti on surveillance data for aggregation into a nation al da tabase . Hospi tals partic ipating in the NNIS System provide general medi cal-surgical inpati ent services to adults or chilu00ad dren requiring acute care. Identi ty of the nearly 300 hospitals currently partic ipating in the NNIS System is confi dential . All NNIS data are collecte d using standardi zed prot ocol s, called u2018u2018surveillance com ponentsu2019 u2019: adult and ped iatric intensive care unit (ICU), high-ris knursery (HRN) , and surgical pati ent. 5-7 The compon ents may be used singly or simultaneously , but once selected , they must be used for a minimum of 1 calendar month. All infecti ons are categori z ed into major and specific infecti on sites using standar d CDC de finition s that include laborat ory and clinical criteria.”, “author” : { “dropping-particle” : “”, “family” : “Solomon”, “given” : “Steven”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Horan”, “given” : “Teresa”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Andrus”, “given” : “Mary”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Edwards”, “given” : “Jonathan”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Emori”, “given” : “Grace”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Fridkin”, “given” : “Scott”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Peavy”, “given” : “Gloria”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tolson”, “given” : “James”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Upadhyayula”, “given” : “Saila”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Yi”, “given” : “Bryan”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “American Journal of Infection Control”, “id” : “ITEM-1”, “issue” : “8”, “issued” : { “date-parts” : “2002” }, “page” : “458-475”, “title” : “National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1992 to June 2002, issued August 2002”, “type” : “article-journal”, “volume” : “30” }, “uris” : “http://www.mendeley.com/documents/?uuid=ac6373ea-4731-4c25-ac96-7b68404c0189” } , “mendeley” : { “formattedCitation” : “(Solomon et al. 2002)”, “plainTextFormattedCitation” : “(Solomon et al. 2002)”, “previouslyFormattedCitation” : “(Solomon et al. 2002)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Solomon et al. 2002). In other hand, the prevalence of MRSA has shown variations between the European countries, while the European antimicrobial surveillance system (EARSS) has reported that the proportion of MRSA isolated from blood between 1999 and 2002 was 41-45% in the UK (Figure 1.3). This discrepancy was observed between countries and also sometimes between hospitals within same country ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.3201/eid1009.040069”, “ISBN” : “1080-6040 (Print)”, “ISSN” : “10806040”, “PMID” : “15498166”, “abstract” : “We explored the variation in proportions of methicillin-resistant Staphylococcus aureus (MRSA) between and within countries participating in the European Antimicrobial Resistance Surveillance System and temporal trends in its occurrence. This system collects routine antimicrobial susceptibility tests for S. aureus. We examined data collected from January 1999 through December 2002 (50,759 isolates from 495 hospitals in 26 countries). MRSA prevalence varied almost 100-fold, from ;1% in northern Europe to ;40% in southern and western Europe. MRSA proportions significantly increased in Belgium, Germany, Ireland, the Netherlands, and the United Kingdom, and decreased in Slovenia. Within countries, MRSA proportions varied between hospitals with highest variance in countries with a prevalence of 5% to 20%. The observed trends should stimulate initiatives to control MRSA at national, regional, and hospital levels. The large differences between hospitals indicate that efforts may be most effective at regional and hospital levels.”, “author” : { “dropping-particle” : “”, “family” : “Tiemersma”, “given” : “Edine W.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Bronzwaer”, “given” : “Stef L.A.M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lyytiku00e4inen”, “given” : “Outi”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Degener”, “given” : “John E.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Schrijnemakers”, “given” : “Paul”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Bruinsma”, “given” : “Nienke”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { 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“non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Whale”, “given” : “M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Emerging Infectious Diseases”, “id” : “ITEM-1”, “issue” : “9”, “issued” : { “date-parts” : “2004” }, “page” : “1627-1634”, “title” : “Methicillin-resistant staphylococcus aureus in Europe, 1999-2002”, “type” : “article-journal”, “volume” : “10” }, “uris” : “http://www.mendeley.com/documents/?uuid=806b2197-5a9b-4c5f-bf8f-c155868c50d4” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1093/jac/dki266”, “ISBN” : “0305-7453 (Print)\r0305-7453 (Linking)”, “ISSN” : “03057453”, “PMID” : “16046464”, “abstract” : “Surveillance of bacteraemia caused by methicillin-resistant Staphylococcus aureus (MRSA) in the UK has involved collection of data from hospital microbiology laboratories via several mechanisms, including a voluntary reporting scheme that has been operational in England and Wales since 1989 and mandatory reporting schemes that have been running independently in England, Wales, Scotland and Northern Ireland since 2001. In addition, surveillance schemes involving panels of participating sentinel laboratories that submit isolates for centralized susceptibility testing, such as the Bacteraemia Resistance Surveillance Programme run by the BSAC, have also been established. Each of these data sources have particular advantages, but they also have their individual limitations, with the result that they each give an incomplete picture if considered in isolation. However, by pooling the findings from these different but complementary surveillance programmes, a much more comprehensive and credible picture of the problem posed by MRSA is produced. These schemes have shown both a dramatic rise in the total numbers of cases of S. aureus bacteraemia reported annually and an increase in the proportion of such cases that involve MRSA (from 2% in 1990 to ;40% in the early 2000s), although the most recent data indicate a slight reversal of these trends. Characterization of isolates of MRSA shows a marked temporal relationship between the rise in MRSA bacteraemias and the emergence and spread of two strains of epidemic MRSA, EMRSA-15 and EMRSA-16. Surveillance and control of MRSA infection continue to be high profile and further developments to the mandatory surveillance system in England are likely in the near future.”, “author” : { “dropping-particle” : “”, “family” : “Johnson”, “given” : “Alan P.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pearson”, “given” : “Andrew”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Duckworth”, “given” : “Georgia”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Antimicrobial Chemotherapy”, “id” : “ITEM-2”, “issue” : “3”, “issued” : { “date-parts” : “2005” }, “page” : “455-462”, “title” : “Surveillance and epidemiology of MRSA bacteraemia in the UK”, “type” : “article”, “volume” : “56” }, “uris” : “http://www.mendeley.com/documents/?uuid=23b344e4-3167-4c3b-91d4-dc19d461ca20” } , “mendeley” : { “formattedCitation” : “(Alan P. Johnson, Pearson, and Duckworth 2005; Tiemersma et al. 2004)”, “plainTextFormattedCitation” : “(Alan P. Johnson, Pearson, and Duckworth 2005; Tiemersma et al. 2004)”, “previouslyFormattedCitation” : “(Alan P. Johnson, Pearson, and Duckworth 2005; Tiemersma et al. 2004)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Alan P. Johnson, Pearson, and Duckworth 2005; Tiemersma et al. 2004).

Figure SEQ Figure * ARABIC 3: The proportion of isolates of Staphylococcus aureus from blood culture that are methicillin resistant, England and Wales (Johnson et al., 2005).However, the most common hospital acquired infections from MRSA are skin and soft tissue infections, bone and joint infections, bloodstream infections, endovascular infections, osteomyelitis and meningitis. These infections are varied from unit to unit within the same hospital. For example, bloodstream and pneumonia infections are most common in ICUs due to hospital acquired MRSA strains ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0924-8579(96)00360-3”, “ISSN” : “09248579”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide important pathogen in nosocomial infections. To investigate the extent of the problem in Taiwan, analysis for the period of 1981u20131994 was carried out of prospective surveillance data from the National Taiwan University Hospital, a major university teaching hospital in Taiwan. The number of nosocomial MRSA infections increased from five in 1981 to 133 in 1994, and the incidence increased from 0.2 episodes/1000 discharges in 1981 to 2.9 episodes/1000 discharges in 1994. The most common infection site was surgical wounds, which accounted for 26.3% of total 577 episodes of nosocomial MRSA infections during the study period. However, bacteraemia has become more and more common during the past 14 years. MRSA infections occured more frequently in patients stayed in the burn unit and other intensive care units than in the general wards. Other than oxacillin, the resistance rate to many other antibiotics also increased in S. aureus strains causing nosocomial infections in this hospital. Vancomycin remained active to all these S. aureus strains, even until 1994.”, “author” : { “dropping-particle” : “”, “family” : “Chang”, “given” : “Shan-Chwen”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Sun”, “given” : “Chun-Chuan”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Yang”, “given” : “Li-Se”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Luh”, “given” : “Kwen-Tay”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hsieh”, “given” : “Wei-Chuan”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “International Journal of Antimicrobial Agents”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “1997” }, “page” : “109-114”, “title” : “Increasing nosocomial infections of methicillin-resistant Staphylococcus aureus at a teaching hospital in Taiwan”, “type” : “article-journal”, “volume” : “8” }, “uris” : “http://www.mendeley.com/documents/?uuid=d0af0fe7-3767-4fe3-b49f-e8e77c021fad” }, { “id” : “ITEM-2”, “itemData” : { “PMID” : “15997484”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) is a common skin coloniser and less commonly causes infection. MRSA colonisation should be contained by infection control measures and not treated. MRSA infections cause the same spectrum of infection as MSSA infections, i.e., skin/soft tissue infections, bone/joint infections, central IV line infections, and acute bacterial endocarditis (native valve/prosthetic valve). There is a discrepancy between in-vitro sensitivity and in-vivo effectiveness with MRSA. To treat MRSA infections, clinicians should select an MRSA drug with proven in-vivo effectiveness, i.e., daptomycin. Linezolid, quinupristin/dalfopristin, minocycline, or vancomycin, and not rely on in-vitro susceptibility data. For MRSA, doxycycline cannot be substituted for minocycline. Linezolid and minocycline are available for oral administration and both are also effective in treating MRSA CNS infections. Vancomycin is being used less due to side effects, (increasing MICs/resistance, VISA/VRSA), and increased VRE prevalence. The most potent anti-MRSA drug at the present time is daptomycin. Daptomycin is useful when rapid/effective therapy of MRSA bacteraemia/endocarditis is necessary. Daptomycin is also useful to treat persistent MRSA bacteraemias/MRSA treatment failures with other drugs, i.e., vancomycin. There is no difference in virulence between MSSA and MRSA infections if treatment is started early and with an agent that has in-vivo effectiveness.”, “author” : { “dropping-particle” : “”, “family” : “Cunha”, “given” : “B A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clin Microbiol Infect”, “id” : “ITEM-2”, “issued” : { “date-parts” : “2005” }, “page” : “33-42”, “title” : “Methicillin-resistant Staphylococcus aureus: clinical manifestations and antimicrobial therapy.”, “type” : “article-journal”, “volume” : “11 Suppl 4” }, “uris” : “http://www.mendeley.com/documents/?uuid=ac413112-6e1d-41e6-87ed-25f4156e85aa” } , “mendeley” : { “formattedCitation” : “(S.-C. Chang et al. 1997; Cunha 2005)”, “plainTextFormattedCitation” : “(S.-C. Chang et al. 1997; Cunha 2005)”, “previouslyFormattedCitation” : “(S.-C. Chang et al. 1997; Cunha 2005)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(S.-C. Chang et al. 1997; Cunha 2005).

SCC mec Types mec gene complex ccr gene complex Size
I B (IS1272- mecA- mecRI)
1 (A1B1)
34kb
II A (IS431- mecA, mecRI – mecI)
2 (A2B2)
53-58kb
III A (IS431- mecA, mecRI – mecI)
3 (A3B3)
67kb
IV B (IS431- mecA- mecRI – IS1272)
2 (A2B2)
20-25kb
V C2 (IS431- mecA- mecRI- IS431)b
5 (C)
28kb
VI B (IS431- mecA- mecRI – IS1272)
4 (A4B4)
20-25kb
VII C1 (IS431- mecA- mecRI- IS431)
5 (C)
28-30kb
VIII A (mecA, mecRI and mecI)
4 (A4B4)
32kb
Table SEQ Table * ARABIC 2: SCCmec types (adapted from IWG-SCC (2009). Difference between C1 and C2, the orientation of IS431upstream of mecA is reversed in C2 mec gene complex.
Risk factors associated with nosocomial MRSA:A well-known of the epidemiological features of MRSA is the foundation of creating an effectual infection control stratagem. There are various risk factors linked with the emergence of MRSA nosocomial infections. Commonly can be associated to host factors, antibiotic pressure and infection control procedures. Those risk factors are older age, male gender, previous hospitalization and introduction to antibiotics, length of hospitalization, length of stay in ICU, and underlying disease. furthermore, pneumonia infections are accompanying with ventilator therapy, and immunosuppressive therapy in ICUs. Invasive devices play role in increasing exposure to nosocomial infection. Intravascular (IV) catheters consider as the main risk factor for MRSA bloodstream infection in ICUs ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/jac/dkf009”, “ISBN” : “14602091”, “ISSN” : “0305-7453”, “PMID” : “12039892”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide. To investigate an association between antimicrobial use and MRSA, a case control study of 121 patients infected with MRSA compared with 123 patients infected with methicillin-susceptible S. aureus (MSSA) was carried out. Antimicrobial use was analysed by three different logistic regression models: all beta-lactam antibiotics, beta-lactam antibiotics grouped in classes and antimicrobial use in grammes. Patients infected with MRSA tended to have more co-morbidities, longer lengths of stay (LOS) and greater exposure to antibiotics than MSSA-infected patients. Multivariate analysis identified levofloxacin odds ratio (OR) 8.01, macrolides (OR 4.06), previous hospitalization (OR 1.95), enteral feedings (OR 2.55), surgery (OR 2.24) and LOS before culture (OR 1.03) as independently associated with MRSA infection. All models were concordant with the exception of macrolides, which were not significant based on the number of grammes administered. There were no significant differences in the types of infection or the attributed mortality in either group. MRSA-infected patients had a significantly longer LOS before infection 18.8 +/- 18.2 compared with 8.4 +/- 6.9 (P ; 0.001) and a significantly longer post-diagnosis LOS 27.8 +/- 32.9 compared with 18.6 +/- 21 (P = 0.01) than MSSA-infected patients.”, “author” : { “dropping-particle” : “”, “family” : “Graffunder”, “given” : “Eileen M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Venezia”, “given” : “Richard a”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Journal of antimicrobial chemotherapy”, “id” : “ITEM-1”, “issue” : “6”, “issued” : { “date-parts” : “2002” }, “page” : “999-1005”, “title” : “Risk factors associated with nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection including previous use of antimicrobials.”, “type” : “article-journal”, “volume” : “49” }, “uris” : “http://www.mendeley.com/documents/?uuid=c6408995-e729-4bc0-9f34-cd655e7da0e1” } , “mendeley” : { “formattedCitation” : “(Graffunder and Venezia 2002)”, “plainTextFormattedCitation” : “(Graffunder and Venezia 2002)”, “previouslyFormattedCitation” : “(Graffunder and Venezia 2002)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Graffunder and Venezia 2002). There are other factors that are associated with the spread of MRSA in hospitals: transferring of patients within or between hospitals, poor communication between hospital units, complications in isolation MRSA patients and new epidemic MRSA strains ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/jac/dkf009”, “ISBN” : “14602091”, “ISSN” : “0305-7453”, “PMID” : “12039892”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide. To investigate an association between antimicrobial use and MRSA, a case control study of 121 patients infected with MRSA compared with 123 patients infected with methicillin-susceptible S. aureus (MSSA) was carried out. Antimicrobial use was analysed by three different logistic regression models: all beta-lactam antibiotics, beta-lactam antibiotics grouped in classes and antimicrobial use in grammes. Patients infected with MRSA tended to have more co-morbidities, longer lengths of stay (LOS) and greater exposure to antibiotics than MSSA-infected patients. Multivariate analysis identified levofloxacin odds ratio (OR) 8.01, macrolides (OR 4.06), previous hospitalization (OR 1.95), enteral feedings (OR 2.55), surgery (OR 2.24) and LOS before culture (OR 1.03) as independently associated with MRSA infection. All models were concordant with the exception of macrolides, which were not significant based on the number of grammes administered. There were no significant differences in the types of infection or the attributed mortality in either group. MRSA-infected patients had a significantly longer LOS before infection 18.8 +/- 18.2 compared with 8.4 +/- 6.9 (P ; 0.001) and a significantly longer post-diagnosis LOS 27.8 +/- 32.9 compared with 18.6 +/- 21 (P = 0.01) than MSSA-infected patients.”, “author” : { “dropping-particle” : “”, “family” : “Graffunder”, “given” : “Eileen M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Venezia”, “given” : “Richard a”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Journal of antimicrobial chemotherapy”, “id” : “ITEM-1”, “issue” : “6”, “issued” : { “date-parts” : “2002” }, “page” : “999-1005”, “title” : “Risk factors associated with nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection including previous use of antimicrobials.”, “type” : “article-journal”, “volume” : “49” }, “uris” : “http://www.mendeley.com/documents/?uuid=c6408995-e729-4bc0-9f34-cd655e7da0e1” } , “mendeley” : { “formattedCitation” : “(Graffunder and Venezia 2002)”, “plainTextFormattedCitation” : “(Graffunder and Venezia 2002)”, “previouslyFormattedCitation” : “(Graffunder and Venezia 2002)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Graffunder and Venezia 2002).

Figure SEQ Figure * ARABIC 4: Number of deaths involving MRSA and S. aureus,Wales, deaths registered in 1993 to 2014 (Source: Office for National Statistics)Those factors contribute to therapeutic failure and morbidity besides rising up the mortality of MRSA among hospitalized patients. It is notable that the main reservoir for MRSA in hospitals colonized are infected patients and healthcare workers. Furthermore, the main path on behalf of transmission of MRSA is through the hands of health care workers (HCWs) in hospitals ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1099/jmm.0.45764-0”, “ISBN” : “0032-5473 (Print)\r0032-5473”, “ISSN” : “00325473”, “PMID” : “12151652”, “abstract” : “Methicillin resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen that causes severe morbidity and mortality worldwide. MRSA strains are endemic in many American and European hospitals and account for 29%-35% of all clinical isolates. Recent studies have documented the increased costs associated with MRSA infection, as well as the importance of colonisation pressure. Surveillance strategies have been proposed especially in high risk areas such as the intensive care unit. Pneumonia and bacteraemia account for the majority of MRSA serious clinical infections, but intra-abdominal infections, osteomyelitis, toxic shock syndrome, food poisoning, and deep tissue infections are also important clinical diseases. The traditional antibiotic therapy for MRSA is a glycopeptide, vancomycin. New antibiotics have been recently released that add to the armamentarium for therapy against MRSA and include linezolid, and quinupristin/dalfopristin, but cost, side effects, and resistance may limit their long term usefulness.”, “author” : { “dropping-particle” : “”, “family” : “Haddadin”, “given” : “A S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Fappiano”, “given” : “S A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lipsett”, “given” : “P A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Postgrad Med J”, “id” : “ITEM-1”, “issue” : “921”, “issued” : { “date-parts” : “2002” }, “page” : “385-392”, “title” : “Methicillin resistant Staphylococcus aureus (MRSA) in the intensive care unit”, “type” : “article-journal”, “volume” : “78” }, “uris” : “http://www.mendeley.com/documents/?uuid=9e55f8fd-b1b8-4fd7-8c80-db706a8edeb1” } , “mendeley” : { “formattedCitation” : “(Haddadin, Fappiano, and Lipsett 2002)”, “plainTextFormattedCitation” : “(Haddadin, Fappiano, and Lipsett 2002)”, “previouslyFormattedCitation” : “(Haddadin, Fappiano, and Lipsett 2002)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Haddadin, Fappiano, and Lipsett 2002).

However, the number of death certificates in England and Wales due to MRSA displayed a constant ascent amongst 1993 and 2005, with an intensely great rise between 2004 and 2005, and descend in 2006 until the recent data in 2014 (Figure 1.4). The age-standardized rate for deaths involving MRSA initially increased, from 5.7 to 40.2 deaths per million population, between 1994 and 2005, but has since fallen to a level similar to that observed in 1994 (Figure 1.5). The rate in 2014 was 8.1 deaths per million ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “ISBN” : “1465-1645 (Print)”, “ISSN” : “1465-1645”, “PMID” : “15615149”, “abstract” : “This article examines trends in infection and mortality from methicillin-resistant Staphylococcus aureus (MRSA) over the period 1993 to 2002. Trends in the number of deaths where MRSA was mentioned on the death certificate were compared with national reporting of microbiologically-confirmed bacteraemia to the Health Protection Agency Communicable Disease Surveillance Centre (CDSC). Alongside national trends, patterns in the place of death were examined. Both the number of deaths and number of laboratory reports increased substantially over the period examined. MRSA mortality rates increased over 15-fold during the period 1993 to 2002. Reporting rates for bacteraemia increased 24-fold.”, “author” : { “dropping-particle” : “”, “family” : “Griffiths”, “given” : “Clare”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lamagni”, “given” : “Theresa L”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Crowcroft”, “given” : “Natasha S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Duckworth”, “given” : “Georgia”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rooney”, “given” : “Cleo”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Health statistics quarterly / Office for National Statistics”, “id” : “ITEM-1”, “issue” : “21”, “issued” : { “date-parts” : “2004” }, “page” : “15-22”, “title” : “Trends in MRSA in England and Wales: analysis of morbidity and mortality data for 1993-2002.”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=a4065d28-915b-4c01-9a33-bc315031a175” }, { “id” : “ITEM-2”, “itemData” : { “ISBN” : “1465-1645”, “ISSN” : “1465-1645”, “PMID” : “17894196”, “abstract” : “This article continues a long tradition of examining alcohol-related deaths by occupation in England and Wales. Results are presented for men and women which show those occupations with the highest and lowest indicators of alcohol-related mortality in 2001-05. For both sexes, many of the occupations with the highest alcohol-related mortality were found among those working in the drinks industry, including publicans and bar staff. Low indicators of alcohol-related deaths were found for men who worked as farmers and drivers, and women who worked with children.”, “author” : { “dropping-particle” : “”, “family” : “Romeri”, “given” : “Ester”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Baker”, “given” : “Allan”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Griffiths”, “given” : “Clare”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “E.”, “given” : “Romeri”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “A.”, “given” : “Baker”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Romeri”, “given” : “Ester”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Baker”, “given” : “Allan”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Griffiths”, “given” : “Clare”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Health statistics quarterly / Office for National Statistics”, “id” : “ITEM-2”, “issue” : “35”, “issued” : { “date-parts” : “2007” }, “page” : “6-12”, “title” : “Alcohol-related deaths by occupation, England and Wales, 2001-05.”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=771f2a05-264a-4819-88ce-542a0fe0c11b” }, { “id” : “ITEM-3”, “itemData” : { “ISSN” : “1465-1645”, “PMID” : “19774832”, “abstract” : “This bulletin presents the latest figures for deaths where Clostridium difficile (C. difficile) infection was mentioned on the death certificate: by sex, age group and place of death, in England and Wales. Figures are presented for deaths registered in 2010, with previously released figures for 2006 to 2009 for comparison purposes. Information is also given about the context and use of the statistics, and the method used to produce them.”, “author” : { “dropping-particle” : “”, “family” : “Office for National Statistics”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Statistical Bulletin”, “id” : “ITEM-3”, “issue” : “August”, “issued” : { “date-parts” : “2011” }, “page” : “1-13”, “title” : “Deaths involving MRSA: England and Wales, 2006 to 2010”, “type” : “article-journal” }, “uris” : “http://www.mendeley.com/documents/?uuid=779b93ac-4a96-4085-b3a8-ae01e3739464” } , “mendeley” : { “formattedCitation” : “(Griffiths et al. 2004; Office for National Statistics 2011; Romeri et al. 2007)”, “plainTextFormattedCitation” : “(Griffiths et al. 2004; Office for National Statistics 2011; Romeri et al. 2007)”, “previouslyFormattedCitation” : “(Griffiths et al. 2004; Office for National Statistics 2011; Romeri et al. 2007)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Griffiths et al. 2004; Office for National Statistics 2011; Romeri et al. 2007).

Figure SEQ Figure * ARABIC 5: Age-standardized rates for deaths involving MRSA and S. aureus, Wales, deaths registered in 1993 to 2014 (Source: Office for National StatisticsEpidemiology of MRSA in the community:MRSA has been considered as a nosocomial pathogen and its presence in the community was uncommon since its first description in 1961 ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0140-6736(09)61999-1”, “ISBN” : “0140-6736”, “ISSN” : “1474-547X”, “PMID” : “20206987”, “abstract” : “Meticillin-resistant Staphylococcus aureus (MRSA) is endemic in hospitals worldwide, and causes substantial morbidity and mortality. Health-care-associated MRSA infections arise in individuals with predisposing risk factors, such as surgery or presence of an indwelling medical device. By contrast, many community-associated MRSA (CA-MRSA) infections arise in otherwise healthy individuals who do not have such risk factors. Additionally, CA-MRSA infections are epidemic in some countries. These features suggest that CA-MRSA strains are more virulent and transmissible than are traditional hospital-associated MRSA strains. The restricted treatment options for CA-MRSA infections compound the effect of enhanced virulence and transmission. Although progress has been made towards understanding emergence of CA-MRSA, virulence, and treatment of infections, our knowledge remains incomplete. Here we review the most up-to-date knowledge and provide a perspective for the future prophylaxis or new treatments for CA-MRSA infections.”, “author” : { “dropping-particle” : “”, “family” : “DeLeo”, “given” : “Frank R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Otto”, “given” : “Michael”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kreiswirth”, “given” : “Barry N.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chambers”, “given” : “Henry F.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Lancet”, “id” : “ITEM-1”, “issue” : “9725”, “issued” : { “date-parts” : “2010” }, “page” : “1557-68”, “title” : “Community-associated meticillin-resistant Staphylococcus aureus.”, “type” : “article-journal”, “volume” : “375” }, “uris” : “http://www.mendeley.com/documents/?uuid=c04b296a-9bea-46f2-912a-0a1cde9f7255” } , “mendeley” : { “formattedCitation” : “(DeLeo et al. 2010)”, “plainTextFormattedCitation” : “(DeLeo et al. 2010)”, “previouslyFormattedCitation” : “(DeLeo et al. 2010)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(DeLeo et al. 2010). However, this concept has been reshaped dramatically over the past 15 years and community associated strains infections are now both prevalent and widespread globally ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0140-6736(09)61999-1”, “ISBN” : “0140-6736”, “ISSN” : “1474-547X”, “PMID” : “20206987”, “abstract” : “Meticillin-resistant Staphylococcus aureus (MRSA) is endemic in hospitals worldwide, and causes substantial morbidity and mortality. Health-care-associated MRSA infections arise in individuals with predisposing risk factors, such as surgery or presence of an indwelling medical device. By contrast, many community-associated MRSA (CA-MRSA) infections arise in otherwise healthy individuals who do not have such risk factors. Additionally, CA-MRSA infections are epidemic in some countries. These features suggest that CA-MRSA strains are more virulent and transmissible than are traditional hospital-associated MRSA strains. The restricted treatment options for CA-MRSA infections compound the effect of enhanced virulence and transmission. Although progress has been made towards understanding emergence of CA-MRSA, virulence, and treatment of infections, our knowledge remains incomplete. Here we review the most up-to-date knowledge and provide a perspective for the future prophylaxis or new treatments for CA-MRSA infections.”, “author” : { “dropping-particle” : “”, “family” : “DeLeo”, “given” : “Frank R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Otto”, “given” : “Michael”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kreiswirth”, “given” : “Barry N.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chambers”, “given” : “Henry F.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Lancet”, “id” : “ITEM-1”, “issue” : “9725”, “issued” : { “date-parts” : “2010” }, “page” : “1557-68”, “title” : “Community-associated meticillin-resistant Staphylococcus aureus.”, “type” : “article-journal”, “volume” : “375” }, “uris” : “http://www.mendeley.com/documents/?uuid=c04b296a-9bea-46f2-912a-0a1cde9f7255” } , “mendeley” : { “formattedCitation” : “(DeLeo et al. 2010)”, “plainTextFormattedCitation” : “(DeLeo et al. 2010)”, “previouslyFormattedCitation” : “(DeLeo et al. 2010)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(DeLeo et al. 2010). Moreover, community associated strains have emerged as a major public health problem around the world. A different strain is occurring at different epidemiological areas, which give a clue of the variety of the genotype and phenotype of this pathogen and how it emerges in community with high prevalence causing diseases from skin infection up to sever pneumonia and fatal cases ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/gbe/evu022”, “ISBN” : “1759-6653 (Electronic)\r1759-6653 (Linking)”, “ISSN” : “17596653”, “PMID” : “24482534”, “abstract” : “Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a major public health problem around the world. In Australia, ST93-IV2B is the dominant CA-MRSA clone and displays significantly greater virulence than other S. aureus. Here, we have examined the evolution of ST93 via genomic analysis of 12 MSSA and 44 MRSA ST93 isolates, collected from around Australia over a 17-year period. Comparative analysis revealed a core genome of 2.6 Mb, sharing greater than 99.7% nucleotide identity. The accessory genome was 0.45 Mb and comprised additional mobile DNA elements, harboring resistance to erythromycin, trimethoprim, and tetracycline. Phylogenetic inference revealed a molecular clock and suggested that a single clone of methicillin susceptible, Panton-Valentine leukocidin (PVL) positive, ST93 S. aureus likely spread from North Western Australia in the early 1970s, acquiring methicillin resistance at least twice in the mid 1990s. We also explored associations between genotype and important MRSA phenotypes including oxacillin MIC and production of exotoxins (u03b1-hemolysin Hla, u03b4-hemolysin Hld, PSMu03b13, and PVL). High-level expression of Hla is a signature feature of ST93 and reduced expression in eight isolates was readily explained by mutations in the agr locus. However, subtle but significant decreases in Hld were also noted over time that coincided with decreasing oxacillin resistance and were independent of agr mutations. The evolution of ST93 S. aureus is thus associated with a reduction in both exotoxin expression and oxacillin MIC, suggesting MRSA ST93 isolates are under pressure for adaptive change. ; “, “author” : { “dropping-particle” : “”, “family” : “Stinear”, “given” : “Timothy P.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Holt”, “given” : “Kathryn E.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chua”, “given” : “Kyra”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Stepnell”, “given” : “Justin”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tuck”, “given” : “Kellie L.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Coombs”, “given” : “Geoffrey”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Harrison”, “given” : “Paul Francis”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Seemann”, “given” : “Torsten”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Howden”, “given” : “Benjamin P.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Genome Biology and Evolution”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “2014” }, “page” : “366-378”, “title” : “Adaptive change inferred from genomic population analysis of the ST93 epidemic clone of community-associated methicillin-resistant Staphylococcus aureus”, “type” : “article-journal”, “volume” : “6” }, “uris” : “http://www.mendeley.com/documents/?uuid=f437b48f-7e5b-437c-aa51-bf3f26f14b97” } , “mendeley” : { “formattedCitation” : “(Stinear et al. 2014)”, “plainTextFormattedCitation” : “(Stinear et al. 2014)”, “previouslyFormattedCitation” : “(Stinear et al. 2014)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Stinear et al. 2014). Several virulence factors of this pathogen are interfering with the occurrence of the infection and its severity.

Community associated strains differ from nosocomial strains at several aspect. First, CA-MRSA strains are sensitive to non-?-lactams antibiotics such as clindamycin, trimethoprim/sulfamethoxazole and doxycycline. Secondly, these strains have genotypes that are different from those of nosocomial strains. Lastly, they have different methicillin-resistance cassettes and often encode PVL ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0140-6736(06)68853-3”, “ISBN” : “1474-547X (Electronic)\n0140-6736 (Linking)”, “ISSN” : “01406736”, “PMID” : “16950365”, “abstract” : “Staphylococcus aureus is a gram-positive bacterium that colonises the skin and is present in the anterior nares in about 25-30% of healthy people.1Dependent on its intrinsic virulence or the ability of the host to contain its opportunistic behaviour, S aureus can cause a range of diseases in man. The bacterium readily acquires resistance against all classes of antibiotics by one of two distinct mechanisms: mutation of an existing bacterial gene or horizontal transfer of a resistance gene from another bacterium. Several mobile genetic elements carrying exogenous antibiotic resistance genes might mediate resistance acquisition.2Of all the resistance traits S aureus has acquired since the introduction of antimicrobial chemotherapy in the 1930s, meticillin resistance is clinically the most important, since a single genetic element confers resistance to the most commonly prescribed class of antimicrobials-the u03b2-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems. u00a9 2006 Elsevier Ltd. All rights reserved.”, “author” : { “dropping-particle” : “”, “family” : “Grundmann”, “given” : “Hajo”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Aires-de-Sousa”, “given” : “Marta”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Boyce”, “given” : “John”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tiemersma”, “given” : “Edine”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Lancet”, “id” : “ITEM-1”, “issue” : “9538”, “issued” : { “date-parts” : “2006” }, “page” : “874-885”, “title” : “Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat”, “type” : “article”, “volume” : “368” }, “uris” : “http://www.mendeley.com/documents/?uuid=d269620c-cda4-4040-91a7-f8df127a6846” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1038/labinvest.3700501”, “ISBN” : “0023-6837 (Print)”, “ISSN” : “0023-6837”, “PMID” : “17146447”, “abstract” : “Community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) infection among individuals without healthcare-associated (HA) risk factors was first recognized about a decade ago. It has now emerged as an epidemic that is responsible for rapidly progressive, fatal diseases including necrotizing pneumonia, severe sepsis and necrotizing fasciitis. Unlike HA-MRSA, CA-MRSA are usually pan-susceptible to non-beta-lactam antimicrobials. In addition to novel methicillin resistance genetic cassettes, many CA-MRSA harbor a phage harboring Panton-Valentine Leukocidin (PVL) genes and some data support the idea that PVL is responsible at least in part for the increased virulence of CA-MRSA. The tight association between the novel methicillin resistance cassettes and PVL phage cannot be explained, as they integrate into distinct sites on the S. aureus chromosome. This paper presents the evidence that CA-MRSA isolates are distinct strains emerging de novo from CA-methicillin susceptible isolates rather than from HA-MRSA isolates that have escaped from the hospital setting and that these novel CA-MRSA isolates may be more virulent than HA-MRSA. The second aim is to outline the progress in understanding the role of PVL in CA-MRSA pathogenesis”, “author” : { “dropping-particle” : “”, “family” : “Boyle-Vavra”, “given” : “S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Daum”, “given” : “R S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Lab Invest”, “id” : “ITEM-2”, “issue” : “0023-6837 (Print)”, “issued” : { “date-parts” : “2007” }, “page” : “3-9”, “title” : “Community-acquired methicillin-resistant Staphylococcus aureus: the role of Panton-Valentine leukocidin”, “type” : “article-journal”, “volume” : “87” }, “uris” : “http://www.mendeley.com/documents/?uuid=e41c8391-318f-4b4b-977c-1a5deb411ac7” } , “mendeley” : { “formattedCitation” : “(Boyle-Vavra and Daum 2007; Grundmann et al. 2006)”, “plainTextFormattedCitation” : “(Boyle-Vavra and Daum 2007; Grundmann et al. 2006)”, “previouslyFormattedCitation” : “(Boyle-Vavra and Daum 2007; Grundmann et al. 2006)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Boyle-Vavra and Daum 2007; Grundmann et al. 2006).There is almost eight classification systems have been applied to categorize community-acquired infections with no standard definition for CA-MRSA ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0928-8244(03)00370-5”, “ISBN” : “0928-8244 (Print)\r0928-8244 (Linking)”, “ISSN” : “09288244”, “PMID” : “15040388”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) emerged in the early 1960s after the acquisition of the methicillin resistance gene mecA, which is carried by the staphylococcal cassette chromosome mec (SCCmec). MRSA seemed to have arisen by multiple introductions of SCCmec into successful methicillin-susceptible S. aureus (MSSA) lineages. MRSA is one of the most common agents of nosocomial infections worldwide increasing the cost and mortality compared to MSSA infections. Little by little, MRSA has acquired resistance to all antibiotics available in clinical practice, which complicates treatment. This situation was further aggravated by the recent reports of vanA-mediated vancomycin-resistant S. aureus. As a reaction to the emergence and spread of multidrug-resistant MRSA worldwide, international surveillance systems such as the CEM/NET initiative have been created. The characterization of over 3000 MRSA isolates from different regions of the world evidenced the existence of only a few epidemic clones spread worldwide, namely the Iberian, Brazilian, Hungarian, New York/Japan, Pediatric and EMRSA-16 clones. It was found that in surveillance or evolutionary studies strains should be characterized by a combination of different typing methods, namely pulsed-field gel electrophoresis, multi-locus sequence typing and SCCmec typing. In recent years, community-acquired MRSA (CA-MRSA) has become a growing public health concern. However, although many authors reported the emergence of CA-MRSA isolates, a standard definition has not been created and the prevalence of MRSA among persons without risk factors seems to remain very low. CA-MRSA has distinct properties compared to epidemic nosocomial MRSA clones and its origin is still unclear. Certain authors suggest there is MRSA transmission from the hospital setting to the community, namely transfer of nosocomial MRSA minor clones or sporadic isolates showing a high degree of similarity with CA-MRSA; others believe CA-MRSA strains represent new acquisitions of SCCmec DNA in susceptible backgrounds. Many questions concerning this extraordinarily versatile and threatening pathogen remain unanswered, needing future investigation. u00a9 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.”, “author” : { “dropping-particle” : “”, “family” : “Aires De Sousa”, “given” : “Marta”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lencastre”, “given” : “Hermu00ednia”, “non-dropping-particle” : “De”, “parse-names” : false, “suffix” : “” } , “container-title” : “FEMS Immunology and Medical Microbiology”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “2004” }, “page” : “101-111”, “title” : “Bridges from hospitals to the laboratory: Genetic portraits of methicillin-resistant Staphylococcus aureus clones”, “type” : “article”, “volume” : “40” }, “uris” : “http://www.mendeley.com/documents/?uuid=392a68fe-2d46-4ebc-803d-9711a35e43fa” } , “mendeley” : { “formattedCitation” : “(Aires De Sousa and De Lencastre 2004)”, “plainTextFormattedCitation” : “(Aires De Sousa and De Lencastre 2004)”, “previouslyFormattedCitation” : “(Aires De Sousa and De Lencastre 2004)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Aires De Sousa and De Lencastre 2004)
Moreover, based on CDC terms and protocol they defines CA-MRSA as an infection with MRSA that lacks of HA-MRSA risk factors including: the isolation of MRSA more than 48 hours after admission, recent surgery, hospitalization history, previous isolation of MRSA and presence of either indwelling catheter or a percutaneous device at the moment of culturing the sample ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/AAC.06449-11”, “ISBN” : “1533-4406 (Electronic)\r0028-4793 (Linking)”, “ISSN” : “1533-4406”, “PMID” : “15814879”, “abstract” : “BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection has emerged in patients who do not have the established risk factors. The national burden and clinical effect of this novel presentation of MRSA disease are unclear. METHODS: We evaluated MRSA infections in patients identified from population-based surveillance in Baltimore and Atlanta and from hospital-laboratory-based sentinel surveillance of 12 hospitals in Minnesota. Information was obtained by interviewing patients and by reviewing their medical records. Infections were classified as community-acquired MRSA disease if no established risk factors were identified. RESULTS: From 2001 through 2002, 1647 cases of community-acquired MRSA infection were reported, representing between 8 and 20 percent of all MRSA isolates. The annual disease incidence varied according to site (25.7 cases per 100,000 population in Atlanta vs. 18.0 per 100,000 in Baltimore) and was significantly higher among persons less than two years old than among those who were two years of age or older (relative risk, 1.51; 95 percent confidence interval, 1.19 to 1.92) and among blacks than among whites in Atlanta (age-adjusted relative risk, 2.74; 95 percent confidence interval, 2.44 to 3.07). Six percent of cases were invasive, and 77 percent involved skin and soft tissue. The infecting strain of MRSA was often (73 percent) resistant to prescribed antimicrobial agents. Among patients with skin or soft-tissue infections, therapy to which the infecting strain was resistant did not appear to be associated with adverse patient-reported outcomes. Overall, 23 percent of patients were hospitalized for the MRSA infection. CONCLUSIONS: Community-associated MRSA infections are now a common and serious problem. These infections usually involve the skin, especially among children, and hospitalization is common”, “author” : { “dropping-particle” : “”, “family” : “Fridkin”, “given” : “S K”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hageman”, “given” : “J C”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Morrison”, “given” : “M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Sanza”, “given” : “L T”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Como-Sabetti”, “given” : “K”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Jernigan”, “given” : “J A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Harriman”, “given” : “K”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Harrison”, “given” : “L H”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lynfield”, “given” : “R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Farley”, “given” : “M M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “N.Engl.J.Med.”, “id” : “ITEM-1”, “issue” : “1533-4406”, “issued” : { “date-parts” : “2005” }, “page” : “1436-1444”, “title” : “Methicillin-resistant Staphylococcus aureus disease in three communities”, “type” : “article-journal”, “volume” : “352” }, “uris” : “http://www.mendeley.com/documents/?uuid=fe3f850c-bd6c-43de-9125-91fb2b1c996b” }, { “id” : “ITEM-2”, “itemData” : { “abstract” : “Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was initially defined as an infection with methicillin-resistant S. aureus (MRSA) in an outpatient or in a patient that manifested infection within 48 hours of hospital admission (1). It was soon recognized that CA-MRSA has unique characteristics not related to time of onset or hospitalization that differentiate it from health careu2013associated MRSA (HA-MRSA). These include epidemiology, presentation, treatment, and genetic profile.”, “author” : { “dropping-particle” : “”, “family” : “Weigelt”, “given” : “Karen J. Brasel and John A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “MRSA”, “id” : “ITEM-2”, “issued” : { “date-parts” : “2010” }, “title” : “Community-Associated MRSA as a Pathogen, MRSA, Informa Healthcare”, “type” : “chapter” }, “uris” : “http://www.mendeley.com/documents/?uuid=d983cac2-7c29-4c7f-94d3-987f2df47a5a” } , “mendeley” : { “formattedCitation” : “(Fridkin et al. 2005; Weigelt 2010)”, “plainTextFormattedCitation” : “(Fridkin et al. 2005; Weigelt 2010)”, “previouslyFormattedCitation” : “(Fridkin et al. 2005; Weigelt 2010)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Fridkin et al. 2005; Weigelt 2010). In fact, the most common CA- MRSA infections are bacteremia, skin and soft tissue infections, toxic shock syndrome, septic arthritis, necrotizing fasciitis and necrotizing pneumonia ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0140-6736(06)68853-3”, “ISBN” : “1474-547X (Electronic)\n0140-6736 (Linking)”, “ISSN” : “01406736”, “PMID” : “16950365”, “abstract” : “Staphylococcus aureus is a gram-positive bacterium that colonises the skin and is present in the anterior nares in about 25-30% of healthy people.1Dependent on its intrinsic virulence or the ability of the host to contain its opportunistic behaviour, S aureus can cause a range of diseases in man. The bacterium readily acquires resistance against all classes of antibiotics by one of two distinct mechanisms: mutation of an existing bacterial gene or horizontal transfer of a resistance gene from another bacterium. Several mobile genetic elements carrying exogenous antibiotic resistance genes might mediate resistance acquisition.2Of all the resistance traits S aureus has acquired since the introduction of antimicrobial chemotherapy in the 1930s, meticillin resistance is clinically the most important, since a single genetic element confers resistance to the most commonly prescribed class of antimicrobials-the u03b2-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems. u00a9 2006 Elsevier Ltd. All rights reserved.”, “author” : { “dropping-particle” : “”, “family” : “Grundmann”, “given” : “Hajo”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Aires-de-Sousa”, “given” : “Marta”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Boyce”, “given” : “John”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tiemersma”, “given” : “Edine”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Lancet”, “id” : “ITEM-1”, “issue” : “9538”, “issued” : { “date-parts” : “2006” }, “page” : “874-885”, “title” : “Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat”, “type” : “article”, “volume” : “368” }, “uris” : “http://www.mendeley.com/documents/?uuid=d269620c-cda4-4040-91a7-f8df127a6846” } , “mendeley” : { “formattedCitation” : “(Grundmann et al. 2006)”, “plainTextFormattedCitation” : “(Grundmann et al. 2006)”, “previouslyFormattedCitation” : “(Grundmann et al. 2006)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Grundmann et al. 2006).

Although, the community associated strains infections have been reported between several society including homeless people, military recruits, competitive athletes, homosexuals, community-based resident, health-care institutions and children in day-care centers ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0140-6736(06)68853-3”, “ISBN” : “1474-547X (Electronic)\n0140-6736 (Linking)”, “ISSN” : “01406736”, “PMID” : “16950365”, “abstract” : “Staphylococcus aureus is a gram-positive bacterium that colonises the skin and is present in the anterior nares in about 25-30% of healthy people.1Dependent on its intrinsic virulence or the ability of the host to contain its opportunistic behaviour, S aureus can cause a range of diseases in man. The bacterium readily acquires resistance against all classes of antibiotics by one of two distinct mechanisms: mutation of an existing bacterial gene or horizontal transfer of a resistance gene from another bacterium. Several mobile genetic elements carrying exogenous antibiotic resistance genes might mediate resistance acquisition.2Of all the resistance traits S aureus has acquired since the introduction of antimicrobial chemotherapy in the 1930s, meticillin resistance is clinically the most important, since a single genetic element confers resistance to the most commonly prescribed class of antimicrobials-the u03b2-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems. u00a9 2006 Elsevier Ltd. All rights reserved.”, “author” : { “dropping-particle” : “”, “family” : “Grundmann”, “given” : “Hajo”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Aires-de-Sousa”, “given” : “Marta”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Boyce”, “given” : “John”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tiemersma”, “given” : “Edine”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Lancet”, “id” : “ITEM-1”, “issue” : “9538”, “issued” : { “date-parts” : “2006” }, “page” : “874-885”, “title” : “Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat”, “type” : “article”, “volume” : “368” }, “uris” : “http://www.mendeley.com/documents/?uuid=d269620c-cda4-4040-91a7-f8df127a6846” } , “mendeley” : { “formattedCitation” : “(Grundmann et al. 2006)”, “plainTextFormattedCitation” : “(Grundmann et al. 2006)”, “previouslyFormattedCitation” : “(Grundmann et al. 2006)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Grundmann et al. 2006). Community associated strains is linked with the production of PVL that is encoded by phage-mediated lukS-PV and lukF-PV genes. The severity of skin and soft tissue infection is because of the production of this toxin ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1038/labinvest.3700501”, “ISBN” : “0023-6837 (Print)”, “ISSN” : “0023-6837”, “PMID” : “17146447”, “abstract” : “Community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) infection among individuals without healthcare-associated (HA) risk factors was first recognized about a decade ago. It has now emerged as an epidemic that is responsible for rapidly progressive, fatal diseases including necrotizing pneumonia, severe sepsis and necrotizing fasciitis. Unlike HA-MRSA, CA-MRSA are usually pan-susceptible to non-beta-lactam antimicrobials. In addition to novel methicillin resistance genetic cassettes, many CA-MRSA harbor a phage harboring Panton-Valentine Leukocidin (PVL) genes and some data support the idea that PVL is responsible at least in part for the increased virulence of CA-MRSA. The tight association between the novel methicillin resistance cassettes and PVL phage cannot be explained, as they integrate into distinct sites on the S. aureus chromosome. This paper presents the evidence that CA-MRSA isolates are distinct strains emerging de novo from CA-methicillin susceptible isolates rather than from HA-MRSA isolates that have escaped from the hospital setting and that these novel CA-MRSA isolates may be more virulent than HA-MRSA. The second aim is to outline the progress in understanding the role of PVL in CA-MRSA pathogenesis”, “author” : { “dropping-particle” : “”, “family” : “Boyle-Vavra”, “given” : “S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Daum”, “given” : “R S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Lab Invest”, “id” : “ITEM-1”, “issue” : “0023-6837 (Print)”, “issued” : { “date-parts” : “2007” }, “page” : “3-9”, “title” : “Community-acquired methicillin-resistant Staphylococcus aureus: the role of Panton-Valentine leukocidin”, “type” : “article-journal”, “volume” : “87” }, “uris” : “http://www.mendeley.com/documents/?uuid=e41c8391-318f-4b4b-977c-1a5deb411ac7” } , “mendeley” : { “formattedCitation” : “(Boyle-Vavra and Daum 2007)”, “plainTextFormattedCitation” : “(Boyle-Vavra and Daum 2007)”, “previouslyFormattedCitation” : “(Boyle-Vavra and Daum 2007)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Boyle-Vavra and Daum 2007).

There are several risk factors attributed to the acquisition of CA-MRSA such overcrowding, compromised skin, common use of broad-spectrum antibiotics, contaminated items, lack of cleanliness and close contact with a person with these risk factors. Health-care facilities are the most possible source for CA-MRSA strains based on the similarities which have been found between infrequent nosocomial-MRSA and community associated-MRSA infections ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0928-8244(03)00370-5”, “ISBN” : “0928-8244 (Print)\r0928-8244 (Linking)”, “ISSN” : “09288244”, “PMID” : “15040388”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) emerged in the early 1960s after the acquisition of the methicillin resistance gene mecA, which is carried by the staphylococcal cassette chromosome mec (SCCmec). MRSA seemed to have arisen by multiple introductions of SCCmec into successful methicillin-susceptible S. aureus (MSSA) lineages. MRSA is one of the most common agents of nosocomial infections worldwide increasing the cost and mortality compared to MSSA infections. Little by little, MRSA has acquired resistance to all antibiotics available in clinical practice, which complicates treatment. This situation was further aggravated by the recent reports of vanA-mediated vancomycin-resistant S. aureus. As a reaction to the emergence and spread of multidrug-resistant MRSA worldwide, international surveillance systems such as the CEM/NET initiative have been created. The characterization of over 3000 MRSA isolates from different regions of the world evidenced the existence of only a few epidemic clones spread worldwide, namely the Iberian, Brazilian, Hungarian, New York/Japan, Pediatric and EMRSA-16 clones. It was found that in surveillance or evolutionary studies strains should be characterized by a combination of different typing methods, namely pulsed-field gel electrophoresis, multi-locus sequence typing and SCCmec typing. In recent years, community-acquired MRSA (CA-MRSA) has become a growing public health concern. However, although many authors reported the emergence of CA-MRSA isolates, a standard definition has not been created and the prevalence of MRSA among persons without risk factors seems to remain very low. CA-MRSA has distinct properties compared to epidemic nosocomial MRSA clones and its origin is still unclear. Certain authors suggest there is MRSA transmission from the hospital setting to the community, namely transfer of nosocomial MRSA minor clones or sporadic isolates showing a high degree of similarity with CA-MRSA; others believe CA-MRSA strains represent new acquisitions of SCCmec DNA in susceptible backgrounds. Many questions concerning this extraordinarily versatile and threatening pathogen remain unanswered, needing future investigation. u00a9 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.”, “author” : { “dropping-particle” : “”, “family” : “Aires De Sousa”, “given” : “Marta”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lencastre”, “given” : “Hermu00ednia”, “non-dropping-particle” : “De”, “parse-names” : false, “suffix” : “” } , “container-title” : “FEMS Immunology and Medical Microbiology”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “2004” }, “page” : “101-111”, “title” : “Bridges from hospitals to the laboratory: Genetic portraits of methicillin-resistant Staphylococcus aureus clones”, “type” : “article”, “volume” : “40” }, “uris” : “http://www.mendeley.com/documents/?uuid=392a68fe-2d46-4ebc-803d-9711a35e43fa” } , “mendeley” : { “formattedCitation” : “(Aires De Sousa and De Lencastre 2004)”, “plainTextFormattedCitation” : “(Aires De Sousa and De Lencastre 2004)”, “previouslyFormattedCitation” : “(Aires De Sousa and De Lencastre 2004)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Aires De Sousa and De Lencastre 2004).

1.7.7 Treatment and control of MRSA:MRSA strains have shown resistance to most ?-lactam antibiotics and more other antimicrobial agents including aminoglycosides, chloramphenicol fluoroquinolones, clindamycin and macrolides ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0924-8579(97)00027-7”, “ISSN” : “09248579”, “PMID” : “18611815”, “abstract” : “The widespread appearance of methicillin resistant Staphylococcus aureus (MRSA) has significantly undermined the efficacy of currently available antibiotic therapies as strains tend to be multi-resistant. Clinicians are therefore faced with a restricted choice in effective anti-MRSA therapies for infection or elimination of carriage. MRSA remain uniformly susceptible to glycopeptides vancomycin and teicoplanin which remain drugs of choice in treatment of infections. Centres with a high incidence of MRSA should use glycopeptides as empirical monotherapies against these organisms. The low toxicity of teicoplanin makes it an alternative for patients unable to tolerate vancomycin. Only mupirocin is truly effective for use as a topical agent in elimination of MRSA colonisation. For systemic use developmental glycopeptides such as daptomycin, MDL 63246, and LY191145 show better in vitro activity than vancomycin. New cephalosporins TOC-39 and FK-037 show promising anti-MRSA potential with low MICs, as does carbapenem BO-2727 which has a high in vitro activity. whether the new cephalosporins and carbapenems with good in vitro and/or in vivo activities against MRSA will be clinically effective remains to be determined. New fluoroquinolones levofloxacin, temafloxacin and sparfloxacin have enhanced in vitro anti-MRSA activity, although the emergence of resistance, and subsequent cross resistance to related compounds during therapy is a problem. BAY 12-8039, DV-7751 and CS-940 are developmental fluoroquinolones with better in vitro activity and lower spontaneous mutation rates than related compounds. Co-trimoxazole shows good in vivo anti-MRSA activity, comparable to vancomycin, however, severe infections do not respond well and many strains are resistant to this drug. Rifampicin has excellent bactericidal activity but rapidly emerging resistance undermines its use as a monotherapy. Its use in a combination therapy offers limited potential as an alternative. Arbekacin shows good in vitro activity against many MRSA isolates, although resistance to related aminoglycosides is a problem. Streptogramins, virginiamicin and RP 59500 (dalfopristin/quinupristin), and the everninomicin SCH 27899, show excellent activity in vitro and in vivo activity against MRSA and real future potential as alternative agents to vancomycin. Azeleic acid and ramoplanin show future potential as agents for topical use against MSRA. In conclusion only vancomycin as a systemic agent and mupirocinu2026”, “author” : { “dropping-particle” : “”, “family” : “Schmitz”, “given” : “Franz Josef”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Jones”, “given” : “Mark E.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “International Journal of Antimicrobial Agents”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “1997” }, “page” : “1-19”, “title” : “Antibiotics for treatment of infections caused by MRSA and elimination of MRSA carriage. What are the choices?”, “type” : “article”, “volume” : “9” }, “uris” : “http://www.mendeley.com/documents/?uuid=5e3f5ca0-5a01-4fa0-8616-e85cbd61787a” } , “mendeley” : { “formattedCitation” : “(Schmitz and Jones 1997)”, “plainTextFormattedCitation” : “(Schmitz and Jones 1997)”, “previouslyFormattedCitation” : “(Schmitz and Jones 1997)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Schmitz and Jones 1997). The glycopeptides introduced as the most effectual agents against MRSA. However, after the emergence of MRSA strains that have low sensitivity to vancomycin (VISA), first reported in 1996 and subsequently VRSA in 2002, has headed to an rising doubts about using vancomycin as the first choice for curing an d treating of MRSA infections ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/S0140-6736(05)78597-4”, “ISSN” : “13407007”, “PMID” : “9492814”, “abstract” : “The evolution and molecular mechanisms of vancomycin resistance in Staphylococcus aureus were reviewed. Case reports and research studies on biochemestry, electron microscopy and molecular biology of Staphylococcus aureus were selected from Medline database and summarized in the following review. After almost 40 years of successful treatment of S. aureus with vancomycin, several cases of clinical failures have been reported (since 1997). S. aureus strains have appeared with intermediate susceptibility (MIC 8-16 microg/ml), as well as strains with heterogeneous resistance (global MIC ; or =4 microg/ml), but with subpopulations of intermediate susceptibility. In these cases, resistance is mediated by cell wall thickening with reduced cross linking. This traps the antibiotic before it reaches its major target, the murein monomers in the cell membrane. In 2002, a total vancomycin resistant strain (MIC ; or =32 microg/ml) was reported with vanA genes from Enterococcus spp. These genes induce the change of D-Ala-D-Ala terminus for D-Ala-D-lactate in the cell wall precursors, leading to loss of affinity for glycopeptides. Vancomycin resistance in S. aureus has appeared; it is mediated by cell wall modifications that trap the antibiotic before it reaches its action site. In strains with total resistance, Enterococcus spp. genes have been acquired that lead to modification of the glycopeptide target.”, “author” : { “dropping-particle” : “”, “family” : “Ito”, “given” : “T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hanaki”, “given” : “H.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hiramatsu”, “given” : “K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Japanese Journal of Chemotherapy”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2000” }, “page” : “7-23”, “title” : “Vancomycin-resistant Staphylococcus aureus”, “type” : “article-journal”, “volume” : “48” }, “uris” : “http://www.mendeley.com/documents/?uuid=87d28a94-7abf-412b-b56a-c6d3f81c20f8” } , “mendeley” : { “formattedCitation” : “(T. Ito, Hanaki, and Hiramatsu 2000)”, “plainTextFormattedCitation” : “(T. Ito, Hanaki, and Hiramatsu 2000)”, “previouslyFormattedCitation” : “(T. Ito, Hanaki, and Hiramatsu 2000)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(T. Ito, Hanaki, and Hiramatsu 2000).

The treatment of MRSA infections importantly depends on the site of infection. In some cases, removing an infected device and draining abscess are much important that antimicrobial therapy ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “PMID” : “15997484”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) is a common skin coloniser and less commonly causes infection. MRSA colonisation should be contained by infection control measures and not treated. MRSA infections cause the same spectrum of infection as MSSA infections, i.e., skin/soft tissue infections, bone/joint infections, central IV line infections, and acute bacterial endocarditis (native valve/prosthetic valve). There is a discrepancy between in-vitro sensitivity and in-vivo effectiveness with MRSA. To treat MRSA infections, clinicians should select an MRSA drug with proven in-vivo effectiveness, i.e., daptomycin. Linezolid, quinupristin/dalfopristin, minocycline, or vancomycin, and not rely on in-vitro susceptibility data. For MRSA, doxycycline cannot be substituted for minocycline. Linezolid and minocycline are available for oral administration and both are also effective in treating MRSA CNS infections. Vancomycin is being used less due to side effects, (increasing MICs/resistance, VISA/VRSA), and increased VRE prevalence. The most potent anti-MRSA drug at the present time is daptomycin. Daptomycin is useful when rapid/effective therapy of MRSA bacteraemia/endocarditis is necessary. Daptomycin is also useful to treat persistent MRSA bacteraemias/MRSA treatment failures with other drugs, i.e., vancomycin. There is no difference in virulence between MSSA and MRSA infections if treatment is started early and with an agent that has in-vivo effectiveness.”, “author” : { “dropping-particle” : “”, “family” : “Cunha”, “given” : “B A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clin Microbiol Infect”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2005” }, “page” : “33-42”, “title” : “Methicillin-resistant Staphylococcus aureus: clinical manifestations and antimicrobial therapy.”, “type” : “article-journal”, “volume” : “11 Suppl 4” }, “uris” : “http://www.mendeley.com/documents/?uuid=ac413112-6e1d-41e6-87ed-25f4156e85aa” } , “mendeley” : { “formattedCitation” : “(Cunha 2005)”, “plainTextFormattedCitation” : “(Cunha 2005)”, “previouslyFormattedCitation” : “(Cunha 2005)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Cunha 2005). Lately, updated guidelines of the usage of prophylaxis and the treatment of MRSA infections in the UK have recommend glycopeptides or linezolid as the first drug of choice to treat MRSA infection including pneumonia and SSTI where bacteremia risk is elevated ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/jac/dkl017”, “abstract” : “These evidence-based guidelines have been produced after a literature review of the treatment and prophylaxis of methicillin-resistant Staphylococcus aureus (MRSA) infection. The guidelines were further informed by antibiotic susceptibility data on MRSA from the UK. Recommendations are given for the treatment of common infections caused by MRSA, elimination of MRSA from carriage sites and prophylaxis of surgical site infection. There are several antibiotics currently available that are suitable for use in the management of this problem and potentially useful new agents are continuing to emerge.”, “author” : { “dropping-particle” : “”, “family” : “Gemmell”, “given” : “Curtis G.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Edwards”, “given” : “David I.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Fraise”, “given” : “Adam P.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gould”, “given” : “F. K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ridgway”, “given” : “Geoff L.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Warren”, “given” : “Rod E.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Joint Working Party of the British Society for Joint Working Party of the British Society for Antimicrobial Chemotherapy”, “given” : “Hospital Infection Society”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Association”, “given” : “Infection Control Nurses”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Journal of antimicrobial chemotherapy”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2006” }, “page” : “589-608”, “title” : “Guidelines for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK.”, “type” : “article-journal”, “volume” : “57” }, “uris” : “http://www.mendeley.com/documents/?uuid=fbbf0c25-5567-43df-ad02-cc4c366c1b4a” }, { “id” : “ITEM-2”, “itemData” : { “abstract” : “These evidence-based guidelines are an updated version of those published in 2006. They have been produced after a literature review of the treatment and prophylaxis of methicillin-resistant Staphylococcus aureus (MRSA). The guidelines aim to complement those recently published for the antibiotic treatment of common and emerging community-onset MRSA infections in the UK. The guidelines have reviewed and updated, where appropriate, previous recommendations, taking into account any changes in the UK epidemiology of MRSA, ongoing national surveillance data and the value of new antistaphylococcal agents licensed for use in UK practice. Emerging therapies that have not been licensed for UK use are not reviewed, but their future potential role has been mentioned where deemed appropriate. Recommendations are given for the treatment of common infections caused by MRSA, elimination of MRSA from carriage sites and prophylaxis of surgical site infection “, “author” : { “dropping-particle” : “”, “family” : “Gould”, “given” : “F.Kate”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Brindle”, “given” : “Richard”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chadwick”, “given” : “Paul R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Fraise”, “given” : “Adam P”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hill”, “given” : “Simon”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Nathwani”, “given” : “Dilip”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ridgway”, “given” : “Geoff L”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spry”, “given” : “Michael J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Warren”, “given” : “Rod E”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “on behalf of the MRSA Working Party of the British Society for Antimicrobial Chemotherapy”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Antimicrobial Chemotherapy”, “id” : “ITEM-2”, “issue” : “5”, “issued” : { “date-parts” : “2009” }, “page” : “849-861”, “title” : “Guidelines (2008) for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the United Kingdom”, “type” : “article-journal”, “volume” : “63” }, “uris” : “http://www.mendeley.com/documents/?uuid=a851e6dc-a828-49aa-82e4-764c389f26ca” } , “mendeley” : { “formattedCitation” : “(Gemmell et al. 2006; F. K. Gould et al. 2009)”, “plainTextFormattedCitation” : “(Gemmell et al. 2006; F. K. Gould et al. 2009)”, “previouslyFormattedCitation” : “(Gemmell et al. 2006; F. K. Gould et al. 2009)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Gemmell et al. 2006; F. K. Gould et al. 2009). Linezolid been recommended for treatment of pneumonia upon its outstanding ability to penetrate into the lungs ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/AAC.46.5.1475-1480.2002”, “ISBN” : “0066-4804”, “ISSN” : “00664804”, “PMID” : “11959585”, “abstract” : “In this study, our objective was to determine the steady-state intrapulmonary concentrations and pharmacokinetic parameters of orally administered linezolid in healthy volunteers. Linezolid (600 mg every 12 h for a total of five doses) was administered orally to 25 healthy adult male subjects. Each subgroup contained five subjects, who underwent bronchoscopy and bronchoalveolar lavage (BAL) 4, 8, 12, 24, or 48 h after administration of the last dose. Blood was obtained for drug assay prior to administration of the first dose and fifth dose and at the completion of bronchoscopy and BAL. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) recovered was calculated by the urea dilution method, and the total number of alveolar cells (AC) was counted in a hemocytometer after cytocentrifugation. Linezolid was measured in plasma by a high-pressure liquid chromatography (HPLC) technique and in BAL specimens and AC by a combined HPLC-mass spectrometry technique. Areas under the concentration-time curves (AUCs) for linezolid in plasma, ELF, and AC were derived by noncompartmental analysis. Half-lives for linezolid in plasma, ELF, and AC were calculated from the elimination rate constants derived from a monoexponential fit of the means of the observed concentrations at each time point. Concentrations (means +/- standard deviations) in plasma, ELF, and AC, respectively, were 7.3 +/- 4.9, 64.3 +/- 33.1, and 2.2 +/- 0.6 microg/ml at the 4-h BAL time point and 7.6 +/- 1.7, 24.3 +/- 13.3, and 1.4 +/- 1.3 microg/ml at the 12-h BAL time point. Linezolid concentrations in plasma, ELF, and AC declined monoexponentially, with half-lives of 6.9, 7.0, and 5.7 h, respectively. For a MIC of 4, the 12-h plasma AUC/MIC and maximum concentration/MIC ratios were 34.6 and 3.9, respectively, and the percentage of time the drug remained above the MIC for the 12-h dosing interval was 100%; the corresponding ratios in ELF were 120 and 16.1, respectively, and the percentage of time the drug remained above the MIC was 100%. The long plasma and intrapulmonary linezolid half-lives and the percentage of time spent above the MIC of 100% of the dosing interval provide a pharmacokinetic rationale for drug administration every 12 h and indicate that linezolid is likely to be an effective agent for the treatment of pulmonary infections.”, “author” : { “dropping-particle” : “”, “family” : “Conte”, “given” : “John E.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Golden”, “given” : “Jeffrey A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kipps”, “given” : “Juliana”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zurlinden”, “given” : “Elisabeth”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Antimicrobial Agents and Chemotherapy”, “id” : “ITEM-1”, “issue” : “5”, “issued” : { “date-parts” : “2002” }, “page” : “1475-1480”, “title” : “Intrapulmonary pharmacokinetics of linezolid”, “type” : “article-journal”, “volume” : “46” }, “uris” : “http://www.mendeley.com/documents/?uuid=4a1e2fad-6918-4cbb-b3a6-8fb9e06fc923” } , “mendeley” : { “formattedCitation” : “(Conte et al. 2002)”, “plainTextFormattedCitation” : “(Conte et al. 2002)”, “previouslyFormattedCitation” : “(Conte et al. 2002)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Conte et al. 2002). Moreover, glycopepides or linezolid is recommended for cases of uncomplicated bacteremia but with longer treatment. Glycopeptide prophylaxis is recommended prior of surgery for patients who have a history with MRSA colonization ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/jac/dkl017”, “abstract” : “These evidence-based guidelines have been produced after a literature review of the treatment and prophylaxis of methicillin-resistant Staphylococcus aureus (MRSA) infection. The guidelines were further informed by antibiotic susceptibility data on MRSA from the UK. Recommendations are given for the treatment of common infections caused by MRSA, elimination of MRSA from carriage sites and prophylaxis of surgical site infection. There are several antibiotics currently available that are suitable for use in the management of this problem and potentially useful new agents are continuing to emerge.”, “author” : { “dropping-particle” : “”, “family” : “Gemmell”, “given” : “Curtis G.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Edwards”, “given” : “David I.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Fraise”, “given” : “Adam P.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gould”, “given” : “F. K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ridgway”, “given” : “Geoff L.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Warren”, “given” : “Rod E.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Joint Working Party of the British Society for Joint Working Party of the British Society for Antimicrobial Chemotherapy”, “given” : “Hospital Infection Society”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Association”, “given” : “Infection Control Nurses”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Journal of antimicrobial chemotherapy”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2006” }, “page” : “589-608”, “title” : “Guidelines for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK.”, “type” : “article-journal”, “volume” : “57” }, “uris” : “http://www.mendeley.com/documents/?uuid=fbbf0c25-5567-43df-ad02-cc4c366c1b4a” }, { “id” : “ITEM-2”, “itemData” : { “abstract” : “These evidence-based guidelines are an updated version of those published in 2006. They have been produced after a literature review of the treatment and prophylaxis of methicillin-resistant Staphylococcus aureus (MRSA). The guidelines aim to complement those recently published for the antibiotic treatment of common and emerging community-onset MRSA infections in the UK. The guidelines have reviewed and updated, where appropriate, previous recommendations, taking into account any changes in the UK epidemiology of MRSA, ongoing national surveillance data and the value of new antistaphylococcal agents licensed for use in UK practice. Emerging therapies that have not been licensed for UK use are not reviewed, but their future potential role has been mentioned where deemed appropriate. Recommendations are given for the treatment of common infections caused by MRSA, elimination of MRSA from carriage sites and prophylaxis of surgical site infection “, “author” : { “dropping-particle” : “”, “family” : “Gould”, “given” : “F.Kate”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Brindle”, “given” : “Richard”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Chadwick”, “given” : “Paul R”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Fraise”, “given” : “Adam P”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hill”, “given” : “Simon”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Nathwani”, “given” : “Dilip”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ridgway”, “given” : “Geoff L”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spry”, “given” : “Michael J”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Warren”, “given” : “Rod E”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “on behalf of the MRSA Working Party of the British Society for Antimicrobial Chemotherapy”, “given” : “”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Antimicrobial Chemotherapy”, “id” : “ITEM-2”, “issue” : “5”, “issued” : { “date-parts” : “2009” }, “page” : “849-861”, “title” : “Guidelines (2008) for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the United Kingdom”, “type” : “article-journal”, “volume” : “63” }, “uris” : “http://www.mendeley.com/documents/?uuid=a851e6dc-a828-49aa-82e4-764c389f26ca” } , “mendeley” : { “formattedCitation” : “(Gemmell et al. 2006; F. K. Gould et al. 2009)”, “plainTextFormattedCitation” : “(Gemmell et al. 2006; F. K. Gould et al. 2009)”, “previouslyFormattedCitation” : “(Gemmell et al. 2006; F. K. Gould et al. 2009)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Gemmell et al. 2006; F. K. Gould et al. 2009).These recommendations take in their account the effectiveness of the antibiotics besides their toxicity, selection of resistant bacteria and cost ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.diagmicrobio.2004.02.002”, “ISBN” : “0954246454”, “ISSN” : “07328893”, “abstract” : “Ch. 1. Introduction / Barry Cookson, Franz-Josef Schmitz and Ad C. Fluit — Ch. 2. Detection of MRSA / Derek Brown and Barry Cookson — Ch. 3. Mechanisms of Methicillin Resistance / Susanne Rohrer, Markus Bischoff, Jutta Rossi and Brigitte Berger-Bachi — Ch. 4. MRSA Resistance Mechanisms and Surveillance Data for Non-betalactams and Non-glycopeptides / Ian Morrissey and David J. Farrell — Ch. 5. Molecular Approaches for the Epidemiological Characterization of Staphylococcus aureus Strains / Willem B. van Leeuwen — Ch. 6. The Molecular Evolution of Methicillin-Resistant Staphylococcus aureus / J. Ross Fitzgerald and James M. Musser — Ch. 7. Population Structure of MRSA / Ad C. Fluit and Franz-Josef Schmitz — Ch. 8. Vancomycin-Resistant Staphylococcus aureus / Longzhu Cui and Keiichi Hiramatsu — Ch. 9. Virulence Mechanisms in MRSA Pathogenesis / Jesse S. Wright III and Richard P. Novick — Ch. 10. Small Colony Variants — Another Mechanism by Which Staphylococcus aureus Can Evade the Immune Response and Antimicrobial Therapy / Christof von Eiff and Karsten Becker — Ch. 11. Treatment of MRSA Infections / Debby Ben-David and Ethan Rubinstein — Ch. 12. Prevention and Control of Methicillin-Resistant Staphylococcus aureus (MRSA) / Uwe Frank — Ch. 13. Concluding Remarks / Ad C. Fluit and Franz-Josef Schmitz.”, “author” : { “dropping-particle” : “”, “family” : “Fluit”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Schmitz”, “given” : “F.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Diagnostic Microbiology and Infectious Disease”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2004” }, “page” : “75”, “title” : “MRSA: current perspectives”, “type” : “chapter”, “volume” : “49” }, “uris” : “http://www.mendeley.com/documents/?uuid=21418d88-96b4-4ace-b1e3-3c1592c6e73f” } , “mendeley” : { “formattedCitation” : “(Fluit and Schmitz 2004)”, “plainTextFormattedCitation” : “(Fluit and Schmitz 2004)”, “previouslyFormattedCitation” : “(Fluit and Schmitz 2004)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Fluit and Schmitz 2004).

The control of MRSA has been given a extreme priority among health- care professionals worldwide ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.jiph.2008.10.001”, “ISBN” : “1876-0341”, “ISSN” : “18760341”, “PMID” : “20701849”, “abstract” : “Healthcare workers may acquire methicillin-resistant Staphylococcus aureus (MRSA) from patients, both hospital and home environments, other healthcare workers, family and public acquaintances, and pets. There is a consensus of case reports and series which now strongly support the role for MRSA-carrying healthcare personnel to serve as a reservoir and as a vehicle of spread within healthcare settings. Carriage may occur at a number of body sites and for short, intermediate, and long terms. A number of approaches have been taken to interrupt the linkage of staff-patient spread, but most emphasis has been placed on handwashing and the treatment of staff MRSA carriers. The importance of healthcare workers in transmission has been viewed with varying degrees of interest, and several logistical problems have arisen when healthcare worker screening is brought to the forefront. There is now considerable support for the screening and treatment of healthcare workers, but it is suggested that the intensity of any such approach must consider available resources, the nature of the outbreak, and the strength of epidemiological associations. The task of assessing healthcare personnel carriage in any context should be shaped with due regard to national and international guidelines, should be honed and practiced according to local needs and experience, and must be patient-oriented. u00a9 2008 King Saud Bin Abdulaziz University for Health Sciences.”, “author” : { “dropping-particle” : “”, “family” : “Cimolai”, “given” : “Nevio”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Infection and Public Health”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “2008” }, “page” : “78-100”, “title” : “The role of healthcare personnel in the maintenance and spread of methicillin-resistant Staphylococcus aureus”, “type” : “article”, “volume” : “1” }, “uris” : “http://www.mendeley.com/documents/?uuid=b7721bcf-7cb9-4f2d-b315-85da2d06c02a” } , “mendeley” : { “formattedCitation” : “(Cimolai 2008)”, “plainTextFormattedCitation” : “(Cimolai 2008)”, “previouslyFormattedCitation” : “(Cimolai 2008)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Cimolai 2008). Although, there is no consent method to control the MRSA infections, three strategies have been recommended for this purpose. First, “Scutari strategy” which is basically based on the standard cleanliness and protective procedures. This strategy is beneficial on nursing homes and small healthcare facilities. Secondly, “Search and Destroy” strategy is appropriate to hospitals that have recently experienced epidemic outbreaks with no history of major problem with MRSA. This strategy is based on isolation of all infected and colonized patients to eliminate MRSA from the surrounded environment. Finlay, “SALT strategy” (Staphylococcus aureus Limitation Technique) is only applicable for non-containable infections, and when resources are limited. This method is appropriate for epidemic situations in which the incidence of infection is low ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/0195-6701(84)90029-X”, “ISSN” : “01956701”, “PMID” : “6084684”, “abstract” : “Three general strategies for the control of Staphylococcus aureus, particularly methicillin-resistant Staph. aureus (MRSA), are described based on experience in Melbourne, Australia from 1975 to 1984, when such strains have been common. The strategies have been named (1) the Scutari Strategy, based on simple hygienic measures and barrier nursing, (2) the search and destroy technique, with strict isolation of all infected and colonized patients, and attempts to eradicate MRSA from the environment, and (3) the SALT strategy (Staph. aureus limitation techniques) with isolation only for non-containable infections, and ‘infectious precautions’ for other MRSA infections and for colonized patients. u00a9 1984.”, “author” : { “dropping-particle” : “”, “family” : “Spicer”, “given” : “W. John”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Hospital Infection”, “id” : “ITEM-1”, “issue” : “SUPPL. A”, “issued” : { “date-parts” : “1984” }, “page” : “45-49”, “title” : “Three strategies in the control of staphylococci including methicillin-resistant Staphylococcus aureus”, “type” : “article-journal”, “volume” : “5” }, “uris” : “http://www.mendeley.com/documents/?uuid=89ec4766-7cbf-45df-b654-80c5f31ad05e” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1111/j.1469-0691.2009.02699.x”, “ISBN” : “1469-0691”, “ISSN” : “14690691”, “PMID” : “19291143”, “abstract” : “Recent efforts to combat infections have focused on pharmaceutical interventions. However, the global spread of antimicrobial resistance calls for the reappraisal of personal and institutional hygiene. Hygiene embodies behavioural and procedural rules that prevent bacterial transmission. Consequently, the chance of spreading bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) is significantly reduced. Hygiene is part of the primacy and totality of patient care, ensuring that no harm is done. Any prevention and control strategy must be underpinned by changes in attitude, embraced by all. The major components of preventing and controlling MRSA include hand and environmental hygiene (as part of standard precautions), patient isolation, and patient/staff decolonization. Improving hand hygiene practice is especially important where the risk of infection is highest, e.g. in intensive care. Physical isolation has two advantages: the physical barrier interrupts transmission, and this barrier emphasizes that precautions are required. With limited isolation facilities, risk assessment should be conducted to indicate which patients should be isolated. Environmental hygiene, although important, has a lower priority than standard precautions. When a patient is ready for discharge (home) or transfer (to another healthcare facility), the overall interests of the patient should take priority. All patients should be informed of their MRSA-positive status as soon as possible. Because of increased mupirocin resistance, a selective approach to decolonization should be taken. When MRSA-positive staff are identified, restricting their professional activity will depend on the nature of their work. Finally, politicians and others need to commit to providing the necessary resources to maximize MRSA prevention and control”, “author” : { “dropping-particle” : “”, “family” : “Humphreys”, “given” : “H.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Grundmann”, “given” : “H.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Skov”, “given” : “R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lucet”, “given” : “J. C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Cauda”, “given” : “R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Microbiology and Infection”, “id” : “ITEM-2”, “issue” : “2”, “issued” : { “date-parts” : “2009” }, “page” : “120-124”, “title” : “Prevention and control of methicillin-resistant Staphylococcus aureus”, “type” : “article”, “volume” : “15” }, “uris” : “http://www.mendeley.com/documents/?uuid=42f759be-5806-405e-8efe-5bc5f956340b” } , “mendeley” : { “formattedCitation” : “(Humphreys et al. 2009; Spicer 1984)”, “plainTextFormattedCitation” : “(Humphreys et al. 2009; Spicer 1984)”, “previouslyFormattedCitation” : “(Humphreys et al. 2009; Spicer 1984)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Humphreys et al. 2009; Spicer 1984).

However, most of studies have stated that the screening of infected and colonized patients, early detection of MRSA, improved hand hygiene and the cautious use of antibiotics, are effectual approaches to control MRSA infections ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/bja/aeh008”, “ISSN” : “0007-0912”, “PMID” : “14665563”, “abstract” : “Methicillin resistant Staphylococcus aureus (MRSA) is endemic within many hospitals worldwide. Critically ill patients on intensive care units have increased risk factors making them especially prone to nosocomially acquired infections. This review addresses the current situation regarding the evolution of MRSA and the techniques for identifying and epidemiologically typing it. It discusses specific risk factors, the morbidity and mortality associated with critically ill patients, and possibilities for future antibiotic treatments. Br J Anaesth 2004; 92: 121-30”, “author” : { “dropping-particle” : “”, “family” : “Hardy”, “given” : “K. J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “British Journal of Anaesthesia”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2004” }, “page” : “121-130”, “title” : “Methicillin resistant Staphylococcus aureus in the critically ill”, “type” : “article-journal”, “volume” : “92” }, “uris” : “http://www.mendeley.com/documents/?uuid=866d3d83-b209-4115-9647-15a62fa55723” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1016/S0140-6736(06)68853-3”, “ISBN” : “1474-547X (Electronic)\n0140-6736 (Linking)”, “ISSN” : “01406736”, “PMID” : “16950365”, “abstract” : “Staphylococcus aureus is a gram-positive bacterium that colonises the skin and is present in the anterior nares in about 25-30% of healthy people.1Dependent on its intrinsic virulence or the ability of the host to contain its opportunistic behaviour, S aureus can cause a range of diseases in man. The bacterium readily acquires resistance against all classes of antibiotics by one of two distinct mechanisms: mutation of an existing bacterial gene or horizontal transfer of a resistance gene from another bacterium. Several mobile genetic elements carrying exogenous antibiotic resistance genes might mediate resistance acquisition.2Of all the resistance traits S aureus has acquired since the introduction of antimicrobial chemotherapy in the 1930s, meticillin resistance is clinically the most important, since a single genetic element confers resistance to the most commonly prescribed class of antimicrobials-the u03b2-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems. u00a9 2006 Elsevier Ltd. All rights reserved.”, “author” : { “dropping-particle” : “”, “family” : “Grundmann”, “given” : “Hajo”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Aires-de-Sousa”, “given” : “Marta”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Boyce”, “given” : “John”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tiemersma”, “given” : “Edine”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Lancet”, “id” : “ITEM-2”, “issue” : “9538”, “issued” : { “date-parts” : “2006” }, “page” : “874-885”, “title” : “Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat”, “type” : “article”, “volume” : “368” }, “uris” : “http://www.mendeley.com/documents/?uuid=d269620c-cda4-4040-91a7-f8df127a6846” }, { “id” : “ITEM-3”, “itemData” : { “DOI” : “10.1016/j.diagmicrobio.2004.02.002”, “ISBN” : “0954246454”, “ISSN” : “07328893”, “abstract” : “Ch. 1. Introduction / Barry Cookson, Franz-Josef Schmitz and Ad C. Fluit — Ch. 2. Detection of MRSA / Derek Brown and Barry Cookson — Ch. 3. Mechanisms of Methicillin Resistance / Susanne Rohrer, Markus Bischoff, Jutta Rossi and Brigitte Berger-Bachi — Ch. 4. MRSA Resistance Mechanisms and Surveillance Data for Non-betalactams and Non-glycopeptides / Ian Morrissey and David J. Farrell — Ch. 5. Molecular Approaches for the Epidemiological Characterization of Staphylococcus aureus Strains / Willem B. van Leeuwen — Ch. 6. The Molecular Evolution of Methicillin-Resistant Staphylococcus aureus / J. Ross Fitzgerald and James M. Musser — Ch. 7. Population Structure of MRSA / Ad C. Fluit and Franz-Josef Schmitz — Ch. 8. Vancomycin-Resistant Staphylococcus aureus / Longzhu Cui and Keiichi Hiramatsu — Ch. 9. Virulence Mechanisms in MRSA Pathogenesis / Jesse S. Wright III and Richard P. Novick — Ch. 10. Small Colony Variants — Another Mechanism by Which Staphylococcus aureus Can Evade the Immune Response and Antimicrobial Therapy / Christof von Eiff and Karsten Becker — Ch. 11. Treatment of MRSA Infections / Debby Ben-David and Ethan Rubinstein — Ch. 12. Prevention and Control of Methicillin-Resistant Staphylococcus aureus (MRSA) / Uwe Frank — Ch. 13. Concluding Remarks / Ad C. Fluit and Franz-Josef Schmitz.”, “author” : { “dropping-particle” : “”, “family” : “Fluit”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Schmitz”, “given” : “F.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Diagnostic Microbiology and Infectious Disease”, “id” : “ITEM-3”, “issue” : “1”, “issued” : { “date-parts” : “2004” }, “page” : “75”, “title” : “MRSA: current perspectives”, “type” : “chapter”, “volume” : “49” }, “uris” : “http://www.mendeley.com/documents/?uuid=21418d88-96b4-4ace-b1e3-3c1592c6e73f” } , “mendeley” : { “formattedCitation” : “(Fluit and Schmitz 2004; Grundmann et al. 2006; Hardy 2004)”, “plainTextFormattedCitation” : “(Fluit and Schmitz 2004; Grundmann et al. 2006; Hardy 2004)”, “previouslyFormattedCitation” : “(Fluit and Schmitz 2004; Grundmann et al. 2006; Hardy 2004)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Fluit and Schmitz 2004; Grundmann et al. 2006; Hardy 2004). Furthermore, the crucial step of controlling MRSA outbreaks is through typing of strains to differentiate between epidemic and sporadic strains ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.diagmicrobio.2004.02.002”, “ISBN” : “0954246454”, “ISSN” : “07328893”, “abstract” : “Ch. 1. Introduction / Barry Cookson, Franz-Josef Schmitz and Ad C. Fluit — Ch. 2. Detection of MRSA / Derek Brown and Barry Cookson — Ch. 3. Mechanisms of Methicillin Resistance / Susanne Rohrer, Markus Bischoff, Jutta Rossi and Brigitte Berger-Bachi — Ch. 4. MRSA Resistance Mechanisms and Surveillance Data for Non-betalactams and Non-glycopeptides / Ian Morrissey and David J. Farrell — Ch. 5. Molecular Approaches for the Epidemiological Characterization of Staphylococcus aureus Strains / Willem B. van Leeuwen — Ch. 6. The Molecular Evolution of Methicillin-Resistant Staphylococcus aureus / J. Ross Fitzgerald and James M. Musser — Ch. 7. Population Structure of MRSA / Ad C. Fluit and Franz-Josef Schmitz — Ch. 8. Vancomycin-Resistant Staphylococcus aureus / Longzhu Cui and Keiichi Hiramatsu — Ch. 9. Virulence Mechanisms in MRSA Pathogenesis / Jesse S. Wright III and Richard P. Novick — Ch. 10. Small Colony Variants — Another Mechanism by Which Staphylococcus aureus Can Evade the Immune Response and Antimicrobial Therapy / Christof von Eiff and Karsten Becker — Ch. 11. Treatment of MRSA Infections / Debby Ben-David and Ethan Rubinstein — Ch. 12. Prevention and Control of Methicillin-Resistant Staphylococcus aureus (MRSA) / Uwe Frank — Ch. 13. Concluding Remarks / Ad C. Fluit and Franz-Josef Schmitz.”, “author” : { “dropping-particle” : “”, “family” : “Fluit”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Schmitz”, “given” : “F.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Diagnostic Microbiology and Infectious Disease”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2004” }, “page” : “75”, “title” : “MRSA: current perspectives”, “type” : “chapter”, “volume” : “49” }, “uris” : “http://www.mendeley.com/documents/?uuid=21418d88-96b4-4ace-b1e3-3c1592c6e73f” } , “mendeley” : { “formattedCitation” : “(Fluit and Schmitz 2004)”, “plainTextFormattedCitation” : “(Fluit and Schmitz 2004)”, “previouslyFormattedCitation” : “(Fluit and Schmitz 2004)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Fluit and Schmitz 2004).

The typing of MRSA:The capability to category isolates of MRSA is a crucial means for well understanding the epidemiology of MRSA and for developing powerful manipulate measures. Inside the ultimate ten years, a range of typing methodologies were developed for use in both clinical and epidemiological studies ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “ISBN” : “0125-1562 (Print)\r0125-1562 (Linking)”, “ISSN” : “01251562”, “PMID” : “17124994”, “abstract” : “Discriminatory powers of various molecular techniques were evaluated for typing of methicillin-resistant Staphylococcus aureus (MRSA) isolated in Siriraj Hospital, Bangkok, Thailand. Thirty MRSA isolates were randomly selected in this study. They were characterized by pulsed-field gel electrophoresis, Clal-mecA and Clal-Tn554 polymorphisms, ribotyping, and PCR-based methods including SCCmec typing, spa and coa gene polymorphism, and repeat units in hypervariable region downstream of mecA. Individual molecular typing technique distinguished those MRSA isolates into 2 to 5 types. Eleven genetic backgrounds of MRSA isolates were elucidated by combination of typing methods with trimethoprim/sulfamethoxazole (TMP/SXT) susceptibility. Combination of all typing methods including TMP/SXT susceptibility yielded a discriminatory index of 0.94. Combination of PCR-based methods and TMP/SXT susceptibility, with the discriminatory index of 0.89, is a practical typing approach suitable for rapid epidemiological investigation of MRSA isolates in a hospital setting.”, “author” : { “dropping-particle” : “”, “family” : “Wilailuckana”, “given” : “Chotechana”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tribuddharat”, “given” : “Chanwit”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tiensasitorn”, “given” : “Chuntima”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Pongpech”, “given” : “Pintip”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Naenna”, “given” : “Penphun”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rugdeekha”, “given” : “Siriporn”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Dhiraputra”, “given” : “Chertsak”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Danchaivijitr”, “given” : “Somwang”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Southeast Asian Journal of Tropical Medicine and Public Health”, “id” : “ITEM-1”, “issue” : “2”, “issued” : { “date-parts” : “2006” }, “page” : “327-334”, “title” : “Discriminatory powers of molecular typing techniques for methicillin-resistant Staphylococcus aureus in a University Hospital, Thailand”, “type” : “article-journal”, “volume” : “37” }, “uris” : “http://www.mendeley.com/documents/?uuid=18a09169-03d1-4661-920e-9b64e78f3d62” } , “mendeley” : { “formattedCitation” : “(Wilailuckana et al. 2006)”, “plainTextFormattedCitation” : “(Wilailuckana et al. 2006)”, “previouslyFormattedCitation” : “(Wilailuckana et al. 2006)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Wilailuckana et al. 2006). In latest years conventional typing methods had been augmented with more than a few molecular typing methods. Those encompass pulsed-field gel electrophoresis (PFGE), plasmid fingerprinting (PF), arbitrarily primed polymerase chain reaction (AP-PCR), multiple locus variable range tandem repeat (VNTR) analysis (MLVA) and multilocus sequence typing (MLST). For any typing method to be precious it have to have high discriminatory strength, be reproducible, cheaper, and easy to apply and interpret ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/jac/40.1.135”, “ISBN” : “0305-7453 (Print)\r0305-7453 (Linking)”, “ISSN” : “03057453”, “PMID” : “13545234”, “abstract” : “Objective: To study markers of progression in a cohort of HIV-infected intravenous drug users (IDU). Design: A prospective epidemiologic study. Setting and patients. We studied progression of HIV infection among 126 IDU attending the Municipal Health Service in Amsterdam. Main outcome measures: Progression was defined as a decline of the CD4 cell count to 30 years relative hazard (RH), 7.7 95% confidence intervals (CI), 1.7-36.0, core antibody negativity RH, 5.3 (95% Cl, 1.6-17.6), CD4 cell count for CD4 cells 350-500 x 10(6)/l, RH, 1.38 (95% Cl, 0.37-5.16); for CD4 cells 200-350 x 10(6)/l, RH, 9.20 (95% Cl, 2.73-31.05) compared with a CD4 count > 500 x 10(6)/l. A lower rate of progression was associated with borrowing used injecting equipment. IDU who reported borrowing injecting equipment between 1980 and baseline 10-99 times or >99 times had a RH of 0.44 (95% Cl, 0.22-0.88) and 0.19 (95% Cl, 0.03-0.37), respectively, compared with IDU who had borrowed <10 times. p24 antigen positivity was more predictive than core antibody negativity in a model with time-dependent variables, the relative risk for p24 antigen-positive participants was 3.5 (95% Cl, 1.3-9.3). Additional analysis of progression to AIDS in a larger group of IDU showed comparable results with regard to the effect of borrowing on progression. Conclusions: Our observation that those IDU who reported borrowing injecting equipment most frequently appeared to have the lowest rate of progression, corrected for some sources of potential confounding, requires further epidemiologic confirmation and extended laboratory studies since other sources of bias might have been present. Baseline CD4 count, age and core antibody or p24 antigen were predictive of progression in IDU. We wish to emphasize that our results do not imply that borrowing should be encouraged, but may have implications for our understanding of HIV pathogenesis.”, “author” : { “dropping-particle” : “”, “family” : “Hiramatsu”, “given” : “K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hanaki”, “given” : “H.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ino”, “given” : “T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Yabuta”, “given” : “K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Oguri”, “given” : “T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tenover”, “given” : “F. C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Antimicrobial Chemotherapy”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “1997” }, “page” : “135-136”, “title” : “Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility 1”, “type” : “article”, “volume” : “40” }, “uris” : “http://www.mendeley.com/documents/?uuid=07357655-673a-471b-8bb5-c5ce18b2e43d” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1053/jhin.1999.0701”, “ISSN” : “0195-6701”, “PMID” : “10706798”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) has spread to all parts of the world. Effective control measures are dependent on a thorough knowledge of the organism’s epidemiology which requires a typing technique that can be universally applied. Many typing methods have been developed for MRSA but none has been adopted as the internationally recognized standard. This review summarizes the information available on each in order to assess their suitability as a reference procedure. The majority of phenotypic and genotypic techniques are not sufficiently discriminatory, reproducible, stable or useful in an outbreak to be acceptable. The methods which do fulfil these requirements and have a potential for standardization, such as pulsed-field gel electrophoresis, binary typing or a combination of more rapid techniques, require further systematic evaluation.”, “author” : { “dropping-particle” : “”, “family” : “Weller”, “given” : “T M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Journal of hospital infection”, “id” : “ITEM-2”, “issue” : “3”, “issued” : { “date-parts” : “2000” }, “page” : “160-172”, “title” : “Methicillin-resistant Staphylococcus aureus typing methods: which should be the international standard?”, “type” : “article-journal”, “volume” : “44” }, “uris” : “http://www.mendeley.com/documents/?uuid=9e54afcf-6b80-43ae-b023-366770517994” }, { “id” : “ITEM-3”, “itemData” : { “DOI” : “10.1128/JCM.41.4.1801-1804.2003”, “ISBN” : “0095-1137”, “ISSN” : “0095-1137”, “PMID” : “12682193”, “abstract” : “The PCR-based methodology applied to multiple-locus variable numbers of tandem repeat (VNTR) analysis was recently shown to be a useful technique for the molecular typing of clinical isolates of several bacterial species. We have adopted this method for the molecular typing of methicillin-resistant Staphylococcus aureus. Five staphylococcal VNTR loci (sdr, clfA, clfB, ssp, and spa) were subjected to analysis, and it was shown that the method allows typing of S. aureus strains with the discriminatory power and reproducibility of pulsed-field gel electrophoresis while at the same time being rapid and applicable to analysis of large numbers of isolates.”, “author” : { “dropping-particle” : “”, “family” : “Sabat”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Krzyszton-Russjan”, “given” : “J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Strzalka”, “given” : “W.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Filipek”, “given” : “R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kosowska”, “given” : “K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hryniewicz”, “given” : “W.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Travis”, “given” : “J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Potempa”, “given” : “J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Clinical Microbiology”, “id” : “ITEM-3”, “issue” : “4”, “issued” : { “date-parts” : “2003” }, “page” : “1801-1804”, “title” : “New method for typing Staphylococcus aureus strains: multiple-locus variable-number tandem repeat analysis of polymorphism and genetic relationships of clinical isolates”, “type” : “article-journal”, “volume” : “41” }, “uris” : “http://www.mendeley.com/documents/?uuid=ba42a868-bc93-4b77-8e42-a4b7382c0c8a” } , “mendeley” : { “formattedCitation” : “(K. Hiramatsu et al. 1997; Sabat et al. 2003; Weller 2000)”, “plainTextFormattedCitation” : “(K. Hiramatsu et al. 1997; Sabat et al. 2003; Weller 2000)”, “previouslyFormattedCitation” : “(K. Hiramatsu et al. 1997; Sabat et al. 2003; Weller 2000)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(K. Hiramatsu et al. 1997; Sabat et al. 2003; Weller 2000).

Mechanism of genetic variability of bacterial genome:
The thought behind all microbiological typing methods is that epidemiological related strains are descended from one antecedent. Consequently, the descendents share the similar, however not essentially identical epidemiological characteristics that are distinct from those of unrelated strains. Consequently, the analysis of such characteristics is helpful for the study of population structures and also the evolution of bacterial species. the steadiness of such characteristics within a strain and therefore the general diversity of species are very important factors for epidemiological typing ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.diagmicrobio.2004.02.002”, “ISBN” : “0954246454”, “ISSN” : “07328893”, “abstract” : “Ch. 1. Introduction / Barry Cookson, Franz-Josef Schmitz and Ad C. Fluit — Ch. 2. Detection of MRSA / Derek Brown and Barry Cookson — Ch. 3. Mechanisms of Methicillin Resistance / Susanne Rohrer, Markus Bischoff, Jutta Rossi and Brigitte Berger-Bachi — Ch. 4. MRSA Resistance Mechanisms and Surveillance Data for Non-betalactams and Non-glycopeptides / Ian Morrissey and David J. Farrell — Ch. 5. Molecular Approaches for the Epidemiological Characterization of Staphylococcus aureus Strains / Willem B. van Leeuwen — Ch. 6. The Molecular Evolution of Methicillin-Resistant Staphylococcus aureus / J. Ross Fitzgerald and James M. Musser — Ch. 7. Population Structure of MRSA / Ad C. Fluit and Franz-Josef Schmitz — Ch. 8. Vancomycin-Resistant Staphylococcus aureus / Longzhu Cui and Keiichi Hiramatsu — Ch. 9. Virulence Mechanisms in MRSA Pathogenesis / Jesse S. Wright III and Richard P. Novick — Ch. 10. Small Colony Variants — Another Mechanism by Which Staphylococcus aureus Can Evade the Immune Response and Antimicrobial Therapy / Christof von Eiff and Karsten Becker — Ch. 11. Treatment of MRSA Infections / Debby Ben-David and Ethan Rubinstein — Ch. 12. Prevention and Control of Methicillin-Resistant Staphylococcus aureus (MRSA) / Uwe Frank — Ch. 13. Concluding Remarks / Ad C. Fluit and Franz-Josef Schmitz.”, “author” : { “dropping-particle” : “”, “family” : “Fluit”, “given” : “C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Schmitz”, “given” : “F.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Diagnostic Microbiology and Infectious Disease”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “2004” }, “page” : “75”, “title” : “MRSA: current perspectives”, “type” : “chapter”, “volume” : “49” }, “uris” : “http://www.mendeley.com/documents/?uuid=21418d88-96b4-4ace-b1e3-3c1592c6e73f” } , “mendeley” : { “formattedCitation” : “(Fluit and Schmitz 2004)”, “plainTextFormattedCitation” : “(Fluit and Schmitz 2004)”, “previouslyFormattedCitation” : “(Fluit and Schmitz 2004)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Fluit and Schmitz 2004).

The genetic diversity among strains is attributed to varieties of mutational process as well as the accumulation of spontaneous or induced point mutations, genetic recombination and therefore the acquisition or loss of mobile genetics components. The latter components, which may confer virulence factors and antibiotic resistance determents, include plasmids, bacteriophages and gene islands ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1073/pnas.161098098”, “ISBN” : “0027-8424 (Print)\r0027-8424 (Linking)”, “ISSN” : “0027-8424”, “PMID” : “11447287”, “abstract” : “An emerging theme in medical microbiology is that extensive variation exists in gene content among strains of many pathogenic bacterial species. However, this topic has not been investigated on a genome scale with strains recovered from patients with well-defined clinical conditions. Staphylococcus aureus is a major human pathogen and also causes economically important infections in cows and sheep. A DNA microarray representing >90% of the S. aureus genome was used to characterize genomic diversity, evolutionary relationships, and virulence gene distribution among 36 strains of divergent clonal lineages, including methicillin-resistant strains and organisms causing toxic shock syndrome. Genetic variation in S. aureus is very extensive, with approximately 22% of the genome comprised of dispensable genetic material. Eighteen large regions of difference were identified, and 10 of these regions have genes that encode putative virulence factors or proteins mediating antibiotic resistance. We find that lateral gene transfer has played a fundamental role in the evolution of S. aureus. The mec gene has been horizontally transferred into distinct S. aureus chromosomal backgrounds at least five times, demonstrating that methicillin-resistant strains have evolved multiple independent times, rather than from a single ancestral strain. This finding resolves a long-standing controversy in S. aureus research. The epidemic of toxic shock syndrome that occurred in the 1970s was caused by a change in the host environment, rather than rapid geographic dissemination of a new hypervirulent strain. DNA microarray analysis of large samples of clinically characterized strains provides broad insights into evolution, pathogenesis, and disease emergence.”, “author” : { “dropping-particle” : “”, “family” : “Fitzgerald”, “given” : “J. R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Sturdevant”, “given” : “D. E.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Mackie”, “given” : “S. M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Gill”, “given” : “S. R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Musser”, “given” : “J. M.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Proceedings of the National Academy of Sciences”, “id” : “ITEM-1”, “issue” : “15”, “issued” : { “date-parts” : “2001” }, “page” : “8821-8826”, “title” : “Evolutionary genomics of Staphylococcus aureus: Insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic”, “type” : “article-journal”, “volume” : “98” }, “uris” : “http://www.mendeley.com/documents/?uuid=7e37feac-b9c6-4749-b181-ef4fb32ef3ed” } , “mendeley” : { “formattedCitation” : “(Fitzgerald et al. 2001)”, “plainTextFormattedCitation” : “(Fitzgerald et al. 2001)”, “previouslyFormattedCitation” : “(Fitzgerald et al. 2001)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Fitzgerald et al. 2001). Although, mutations are mainly caused by mutagenic agents, together with environmental factors (e.g. chemicals, radiation and ultraviolet light (UV)) and errors that occur spontaneously throughout DNA replication. The UV, for instance, can form T dimers (TT) on the same strand of the DNA. The T dimers cannot act as a templet for DNA polymerases and such dimerization thus is fatal by preventing of the suitable functioning of polymerases. Moreover, some chemical mutagens such as hydroxylamine (NH2OH) can modify cytosine to uracil that pairs with adenine instead of guanine while acridine (C13H9N) causes frame-shift mutations by base deletion or base addition mutations. The spontaneous mutations can be caused by DNA polymerases through mismatched base insertion during DNA replication resulting in changes in the base sequence ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1017/CBO9781107415324.004”, “ISBN” : “10: 0-7167-3136-3”, “ISSN” : “1098-6596”, “PMID” : “25246403”, “abstract” : “Modern biology is rooted in an understanding of the molecules within cells and of the interactions between cells that allow construction of multicellular organisms. The more we learn about the structure, function, and development of different organisms, the more we recognize that all life processes exhibit remarkable similarities. Molecular Cell Biology concentrates on the macromolecules and reactions studied by biochemists, the processes described by cell biologists, and the gene control pathways identified by molecular biologists and geneticists. In this millennium, two gathering forces will reshape molecular cell biology: genomics, the complete DNA sequence of many organisms, and proteomics, a knowledge of all the possible shapes and functions that proteins employ. All the concepts of molecular cell biology continue to be derived from experiments, and powerful experimental tools that allow the study of living cells and organisms at higher and higher levels of resolution are being developed constantly. In this fourth edition, we address the current state of molecular cell biology and look forward to what further exploration will uncover in the twenty-first century.”, “author” : { “dropping-particle” : “”, “family” : “Lodish”, “given” : “Harvey”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Berk”, “given” : “Arnold”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zipursky”, “given” : “S Lawrence”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Matsudaira”, “given” : “Paul”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Baltimore”, “given” : “David”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Darnell”, “given” : “James”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “New York: W. H. Freeman”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2000” }, “number-of-pages” : “Section 11.4”, “title” : “Molecular Cell Biology. 4th edition”, “type” : “book” }, “uris” : “http://www.mendeley.com/documents/?uuid=d4d3dff1-dac7-49e3-9cfe-7d9a52679a2d” } , “mendeley” : { “formattedCitation” : “(Lodish et al. 2000)”, “plainTextFormattedCitation” : “(Lodish et al. 2000)”, “previouslyFormattedCitation” : “(Lodish et al. 2000)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Lodish et al. 2000). Three kinds of replication errors are characterized. First, single-base mispairs resulting in a base substation. Second, single-base bulges leading to a single-base frameshift. Third, multiple-base mismatches resulting in a sequence substitution. These changes throughout the DNA replication play important role in bacterial evolution and thus in bacterial genetic diversities ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/CMR.14.3.547”, “ISBN” : “0893-8512 (Print)\r0893-8512 (Linking)”, “ISSN” : “0893-8512”, “PMID” : “11432813”, “abstract” : “Currently, genetic typing of microorganisms is widely used in several major fields of microbiological research. Taxonomy, research aimed at elucidation of evolutionary dynamics or phylogenetic relationships, population genetics of microorganisms, and microbial epidemiology all rely on genetic typing data for discrimination between genotypes. Apart from being an essential component of these fundamental sciences, microbial typing clearly affects several areas of applied microbiological research. The epidemiological investigation of outbreaks of infectious diseases and the measurement of genetic diversity in relation to relevant biological properties such as pathogenicity, drug resistance, and biodegradation capacities are obvious examples. The diversity among nucleic acid molecules provides the basic information for all fields described above. However, researchers in various disciplines tend to use different vocabularies, a wide variety of different experimental methods to monitor genetic variation, and sometimes widely differing modes of data processing and interpretation. The aim of the present review is to summarize the technological and fundamental concepts used in microbial taxonomy, evolutionary genetics, and epidemiology. Information on the nomenclature used in the different fields of research is provided, descriptions of the diverse genetic typing procedures are presented, and examples of both conceptual and technological research developments for Escherichia coli are included. Recommendations for unification of the different fields through standardization of laboratory techniques are made.”, “author” : { “dropping-particle” : “”, “family” : “Struelens”, “given” : “Marc”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Struelens”, “given” : “Marc”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Verbrugh”, “given” : “Henri”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Verbrugh”, “given” : “Henri”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tibayrenc”, “given” : “Michel”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tibayrenc”, “given” : “Michel”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Taxonomy”, “given” : “Problems With Microbial”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Taxonomy”, “given” : “Problems With Microbial”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Genetics”, “given” : “Concepts O F Evolutionary”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Genetics”, “given” : “Concepts O F Evolutionary”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Recombination”, “given” : “Genetic”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Recombination”, “given” : “Genetic”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Clones”, “given” : “From Microbial Isolates T O”, 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“dropping-particle” : “”, “family” : “Epidemiologist”, “given” : “T H E Microbial”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Epidemiology”, “given” : “Research a T T H E Interface O F”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Epidemiology”, “given” : “Research a T T H E Interface O F”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Genetics”, “given” : “Population”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Genetics”, “given” : “Population”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Evolution”, “given” : “Experimental”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Evolution”, “given” : “Experimental”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Plasticity”, “given” : “Genome”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Plasticity”, “given” : “Genome”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Studies”, “given” : “Contingency”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Studies”, “given” : “Contingency”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Variation”, “given” : “Genomic”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Variation”, “given” : “Genomic”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Potential”, “given” : “Commensal Bacterium With Pathogenic”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Potential”, “given” : “Commensal Bacterium With Pathogenic”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Epidemiology”, “given” : “Standardization O F Techniques Used F O R Microbial”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Epidemiology”, “given” : “Standardization O F Techniques Used F O R Microbial”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Genetics”, “given” : “Evolutionary”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Genetics”, “given” : “Evolutionary”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Interpretation”, “given” : “Data”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Interpretation”, “given” : “Data”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Collections”, “given” : “Reference”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Collections”, “given” : “Reference”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Research”, “given” : “Basic”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Research”, “given” : “Basic”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “The”, “given” : “Introduction”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “The”, “given” : “Introduction”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Microbiology”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2001” }, “page” : “547-560”, “title” : “Role of Genomic Typing in Taxonomy, Evolutionary Genetics, and Microbial Epidemiology”, “type” : “article-journal”, “volume” : “14” }, “uris” : “http://www.mendeley.com/documents/?uuid=a369177e-f136-40bb-ac1a-85cc51c8c105” } , “mendeley” : { “formattedCitation” : “(Struelens et al. 2001)”, “plainTextFormattedCitation” : “(Struelens et al. 2001)”, “previouslyFormattedCitation” : “(Struelens et al. 2001)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Struelens et al. 2001).

However, S. aureus clones arise more often (about 15-fold) by point mutation than by recombination, and that large chromosomal replacements might influence the long-term evolution of this species ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/JB.185.11.3307-3316.2003”, “ISBN” : “0021-9193 (Print)”, “ISSN” : “00219193”, “PMID” : “12754228”, “abstract” : “Staphylococcus aureus is an important human pathogen and represents a growing public health burden owing to the emergence and spread of antibiotic-resistant clones, particularly within the hospital environment. Despite this, basic questions about the evolution and population biology of the species, particularly with regard to the extent and impact of homologous recombination, remain unanswered. We address these issues through an analysis of sequence data obtained from the characterization by multilocus sequence typing (MLST) of 334 isolates of S. aureus, recovered from a well-defined population, over a limited time span. We find no significant differences in the distribution of multilocus genotypes between strains isolated from carriers and those from patients with invasive disease; there is, therefore, no evidence from MLST data, which index variation within the stable “core” genome, for the existence of hypervirulent clones of this pathogen. Examination of the sequence changes at MLST loci during clonal diversification shows that point mutations give rise to new alleles at least 15-fold more frequently than does recombination. This contrasts with the naturally transformable species Neisseria meningitidis and Streptococcus pneumoniae, in which alleles change between 5- and 10-fold more frequently by recombination than by mutation. However, phylogenetic analysis suggests that homologous recombination does contribute toward the evolution of this species over the long term. Finally, we note a striking excess of nonsynonymous substitutions in comparisons between isolates belonging to the same clonal complex compared to isolates belonging to different clonal complexes, suggesting that the removal of deleterious mutations by purifying selection may be relatively slow.”, “author” : { “dropping-particle” : “”, “family” : “Feil”, “given” : “Edward J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Cooper”, “given” : “Jessica E.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Grundmann”, “given” : “Hajo”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Robinson”, “given” : “D. Ashley”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Enright”, “given” : “Mark C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Berendt”, “given” : “Tony”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Peacock”, “given” : “Sharon J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Smith”, “given” : “John Maynard”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Murphy”, “given” : “Michael”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Spratt”, “given” : “Brian G.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Moore”, “given” : “Catrin E.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Day”, “given” : “Nicholas P.J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Bacteriology”, “id” : “ITEM-1”, “issue” : “11”, “issued” : { “date-parts” : “2003” }, “page” : “3307-3316”, “title” : “How clonal is Staphylococcus aureus?”, “type” : “article-journal”, “volume” : “185” }, “uris” : “http://www.mendeley.com/documents/?uuid=084797c8-8bb2-4a3f-94b6-27c3c98c08e1” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1111/j.1469-0691.2004.00768.x”, “ISSN” : “1198-743X”, “PMID” : “14759234”, “abstract” : “The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in many countries is increasing and, in hospitals in some areas, more than half of all S. aureus disease isolates are MRSA. MRSA strains are becoming increasingly multiresistant, and have recently developed resistance to vancomycin, used successfully to treat MRSA for more than 30 years. This review summarises recent studies that have elucidated the evolutionary history of MRSA. The first MRSA isolate evolved from a sensitive, epidemic strain prevalent in Europe, and its progeny-the first MRSA clone-quickly spread to other continents. Analyses of epidemic MRSA isolates from hospitals in different countries by molecular methods, including multilocus sequence typing (MLST) and DNA microarray analysis, reveal that MRSA strains have evolved separately within five distinct epidemic, sensitive lineages. However, resistance has been transferred to S. aureus on many more than five occasions, as some lineages have acquired different structural types of the element carrying the methicillin resistance gene. The emergence of MRSA as a community pathogen has been noted in several countries, and MLST and SCCmec typing have been used to demonstrate that community-acquired MRSA strains are typically related only distantly to hospital MRSA strains, and thus represent novel acquisitions of SCCmec.”, “author” : { “dropping-particle” : “”, “family” : “Robinson”, “given” : “D a”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Enright”, “given” : “M C”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases”, “id” : “ITEM-2”, “issue” : “2”, “issued” : { “date-parts” : “2004” }, “page” : “92-97”, “title” : “Multilocus sequence typing and the evolution of methicillin-resistant Staphylococcus aureus.”, “type” : “article-journal”, “volume” : “10” }, “uris” : “http://www.mendeley.com/documents/?uuid=d42739ff-56db-40f0-abc1-dd0436e15d3a” } , “mendeley” : { “formattedCitation” : “(Feil et al. 2003; Robinson and Enright 2004)”, “plainTextFormattedCitation” : “(Feil et al. 2003; Robinson and Enright 2004)”, “previouslyFormattedCitation” : “(Feil et al. 2003; Robinson and Enright 2004)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Feil et al. 2003; Robinson and Enright 2004). The SCCmec cassette is compose of a large group of mobile genetic elements whose diversity result of an extensive recombination. The SCCmec contains the mec gene (methicillin-resistance gene) and other mobile genetic elements include : transposons, plasmids and insertion sequences. SCCmec is playing an important role in microbial evolution by indorsing the genetic diversity through horizontally transferred within Staphylococcus species ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/JCM.41.4.1574-1585.2003”, “ISBN” : “0095-1137 (Print)\r0095-1137 (Linking)”, “ISSN” : “00951137”, “PMID” : “12682148”, “abstract” : “Pulsed-fieldgel electrophoresis (PFGE) is the most common genotypic method used in reference and clinical laboratories for typing methicillin-resistant Staphylococcus aureus (MRSA). Many different protocols have been developed in laboratories that have extensive experience with the technique and have established national databases. However, the comparabilities of the different European PFGE protocols for MRSA and of the various national MRSA clones themselves had not been addressed until now. This multinational European Union (EU) project has established for the first time a European database of representative epidemic MRSA (EMRSA) strains and has compared them by using a new “harmonized” PFGE protocol developed by a consensus approach that has demonstrated sufficient reproducibility to allow the successful comparison of pulsed-field gels between laboratories and the tracking of strains around the EU. In-house protocols from 10 laboratories in eight European countries were compared by each center with a “gold standard” or initial harmonized protocol in which many of the parameters had been standardized. The group found that it was not important to standardize some elements of the protocol, such as the type of agarose, DNA block preparation, and plug digestion. Other elements were shown to be critical, namely, a standard gel volume and concentration of agarose, the DNA concentration in the plug, the ionic strength and volume of running buffer used, the running temperature, the voltage, and the switching times of electrophoresis. A new harmonized protocol was agreed on, further modified in a pilot study in two laboratories, and finally tested by all others. Seven laboratories’ gels were found to be of sufficiently good quality to allow comparison of the strains by using a computer software program, while two gels could not be analyzed because of inadequate destaining and DNA overloading. Good-quality gels and inclusion of an internal quality control strain are essential before attempting intercenter PFGE comparisons. A number of clonally related strains have been shown to be present in multiple countries throughout Europe. The well-known Iberian clone has been demonstrated in Belgium, Finland, France, Germany, and Spain (and from the wider HARMONY collection in Portugal, Slovenia, and Sweden). Strains from the United Kingdom (EMRSA-15 and -16) have been identified in several othercountries, and other clonally related strains have also been identified. Thiu2026″, “author” : { “dropping-particle” : “”, “family” : “Murchan”, “given” : “Stephen”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kaufmann”, “given” : “Mary Elizabeth”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Deplano”, “given” : “Ariane”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ryck”, “given” : “Raf”, “non-dropping-particle” : “De”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Struelens”, “given” : “Marc”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zinn”, “given” : “Christina Elsberg”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Fussing”, “given” : “Vivian”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Salmenlinna”, “given” : “Saara”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Vuopio-Varkila”, “given” : “Jaana”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Solh”, “given” : “Nu00e9vine”, “non-dropping-particle” : “El”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Cuny”, “given” : “Christina”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Witte”, “given” : “Wolfgang”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tassios”, “given” : “Panayotis T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Legakis”, “given” : “Nikolas”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Leeuwen”, “given” : “Willem”, “non-dropping-particle” : “Van”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Belkum”, “given” : “Alex”, “non-dropping-particle” : “Van”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Vindel”, “given” : “Anna”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Laconcha”, “given” : “Idoia”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Garaizar”, “given” : “Javier”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Haeggman”, “given” : “Saara”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Olsson-Liljequist”, “given” : “Barbro”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ransjo”, “given” : “Ulrika”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Coombes”, “given” : “Geoffrey”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Cookson”, “given” : “Barry”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Clinical Microbiology”, “id” : “ITEM-1”, “issue” : “4”, “issued” : { “date-parts” : “2003” }, “page” : “1574-1585”, “title” : “Harmonization of pulsed-field gel electrophoresis protocols for epidemiological typing of strains of methicillin-resistant Staphylococcus aureus: A single approach developed by consensus in 10 European laboratories and its application for tracing the spre”, “type” : “article-journal”, “volume” : “41” }, “uris” : “http://www.mendeley.com/documents/?uuid=ba1f5804-31d4-46e8-ab7c-fdf6602261d0” } , “mendeley” : { “formattedCitation” : “(Murchan et al. 2003)”, “plainTextFormattedCitation” : “(Murchan et al. 2003)”, “previouslyFormattedCitation” : “(Murchan et al. 2003)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Murchan et al. 2003).

Typing methods vary of their capability to display and define genetic adjustments not only between species, however additionally between strains within a single species. That is contemplated in variations among the resolving strength of the numerous typing strategies. For example, MLST is less discriminatory than PFGE for the analysis of S. aureus in hospital outbreaks, reflective the actual fact that the evolution of diversity over short time periods is more possible to result from the positive selection pressure of virulence or antibiotic resistance genes based on mobile genetics elements genes, than for spontaneous mutations in housekeeping genes ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1128/CMR.00025-05”, “ISSN” : “08938512”, “PMID” : “16847083”, “abstract” : “Nosocomial infections are an important source of morbidity and mortality in hospital settings, afflicting an estimated 2 million patients in United States each year. This number represents up to 5% of hospitalized patients and results in an estimated 88,000 deaths and 4.5 billion dollars in excess health care costs. Increasingly, hospital-acquired infections with multidrug-resistant pathogens represent a major problem in patients. Understanding pathogen relatedness is essential for determining the epidemiology of nosocomial infections and aiding in the design of rational pathogen control methods. The role of pathogen typing is to determine whether epidemiologically related isolates are also genetically related. To determine molecular relatedness of isolates for epidemiologic investigation, new technologies based on DNA, or molecular analysis, are methods of choice. These DNA-based molecular methodologies include pulsed-field gel electrophoresis (PFGE), PCR-based typing methods, and multilocus sequence analysis. Establishing clonality of pathogens can aid in the identification of the source (environmental or personnel) of organisms, distinguish infectious from noninfectious strains, and distinguish relapse from reinfection. The integration of molecular typing with conventional hospital epidemiologic surveillance has been proven to be cost-effective due to the associated reduction in the number of nosocomial infections. Cost-effectiveness is maximized through the collaboration of the laboratory, through epidemiologic typing, and the infection control department during epidemiologic investigations.”, “author” : { “dropping-particle” : “”, “family” : “Singh”, “given” : “Aparajita”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “V.”, “family” : “Goering”, “given” : “Richard”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Simjee”, “given” : “Shabbir”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Foley”, “given” : “Steven L.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Zervos”, “given” : “Marcus J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical Microbiology Reviews”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2006” }, “page” : “512-530”, “title” : “Application of molecular techniques to the study of hospital infection”, “type” : “article”, “volume” : “19” }, “uris” : “http://www.mendeley.com/documents/?uuid=8212a4b8-f4d1-494d-b44b-a35d7cc224b0” } , “mendeley” : { “formattedCitation” : “(Singh et al. 2006)”, “plainTextFormattedCitation” : “(Singh et al. 2006)”, “previouslyFormattedCitation” : “(Singh et al. 2006)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Singh et al. 2006).

Phenotyping methods:Phenotyping methods are used to represent the products of gene expression as a way to become aware of a species or to discriminate among strains, and that include biochemical profiles, antibiogram profiles, phage typing and the presence of surface antigens and protein analysis. Although, there are limitations in using those methods significantly for typing MRSA strains because they’re motivated by using growth situations and epigenetic modifications ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/jac/40.1.135”, “ISBN” : “0305-7453 (Print)\r0305-7453 (Linking)”, “ISSN” : “03057453”, “PMID” : “13545234”, “abstract” : “Objective: To study markers of progression in a cohort of HIV-infected intravenous drug users (IDU). Design: A prospective epidemiologic study. Setting and patients. We studied progression of HIV infection among 126 IDU attending the Municipal Health Service in Amsterdam. Main outcome measures: Progression was defined as a decline of the CD4 cell count to 30 years relative hazard (RH), 7.7 95% confidence intervals (CI), 1.7-36.0, core antibody negativity RH, 5.3 (95% Cl, 1.6-17.6), CD4 cell count for CD4 cells 350-500 x 10(6)/l, RH, 1.38 (95% Cl, 0.37-5.16); for CD4 cells 200-350 x 10(6)/l, RH, 9.20 (95% Cl, 2.73-31.05) compared with a CD4 count > 500 x 10(6)/l. A lower rate of progression was associated with borrowing used injecting equipment. IDU who reported borrowing injecting equipment between 1980 and baseline 10-99 times or >99 times had a RH of 0.44 (95% Cl, 0.22-0.88) and 0.19 (95% Cl, 0.03-0.37), respectively, compared with IDU who had borrowed <10 times. p24 antigen positivity was more predictive than core antibody negativity in a model with time-dependent variables, the relative risk for p24 antigen-positive participants was 3.5 (95% Cl, 1.3-9.3). Additional analysis of progression to AIDS in a larger group of IDU showed comparable results with regard to the effect of borrowing on progression. Conclusions: Our observation that those IDU who reported borrowing injecting equipment most frequently appeared to have the lowest rate of progression, corrected for some sources of potential confounding, requires further epidemiologic confirmation and extended laboratory studies since other sources of bias might have been present. Baseline CD4 count, age and core antibody or p24 antigen were predictive of progression in IDU. We wish to emphasize that our results do not imply that borrowing should be encouraged, but may have implications for our understanding of HIV pathogenesis.”, “author” : { “dropping-particle” : “”, “family” : “Hiramatsu”, “given” : “K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hanaki”, “given” : “H.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ino”, “given” : “T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Yabuta”, “given” : “K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Oguri”, “given” : “T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tenover”, “given” : “F. C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Antimicrobial Chemotherapy”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “1997” }, “page” : “135-136”, “title” : “Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility 1”, “type” : “article”, “volume” : “40” }, “uris” : “http://www.mendeley.com/documents/?uuid=07357655-673a-471b-8bb5-c5ce18b2e43d” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1128/JCM.02402-06”, “ISBN” : “0095-1137 (Print)\r0095-1137 (Linking)”, “ISSN” : “00951137”, “PMID” : “17428929”, “abstract” : “We analyzed a representative sample of methicillin-resistant Staphylococcus aureus (MRSA) from 11 European countries (referred to as the HARMONY collection) using three molecular typing methods used within the HARMONY group to examine their usefulness for large, multicenter MRSA surveillance networks that use these different laboratory methodologies. MRSA isolates were collected based on their prevalence in each center and their genetic diversity, assessed by pulsed-field gel electrophoresis (PFGE). PFGE groupings (< or = 3 bands difference between patterns) were compared to those made by sequencing of the variable repeats in the protein A gene spa and clonal designations based on multilocus sequence typing (MLST), combined with PCR analysis of the staphylococcal chromosome cassette containing the mec genes involved in methicillin resistance (SCCmec). A high level of discrimination was achieved using each of the three methodologies, with discriminatory indices between 89.5% and 91.9% with overlapping 95% confidence intervals. There was also a high level of concordance of groupings made using each method. MLST/SCCmec typing distinguished 10 groups containing at least two isolates, and these correspond to the majority of nosocomial MRSA clones described in the literature. PFGE and spa typing resolved 34 and 31 subtypes, respectively, within these 10 MRSA clones, with each subtype differing only slightly from the most common pattern using each method. The HARMONY group has found that the methods used in this study differ in their availability and affordability to European centers involved in MRSA surveillance. Here, we demonstrate that the integration of such technologies is achievable, although common protocols (such as we have developed for PFGE) may also be important, as is the use of centralized Internet sites to facilitate data analysis. PFGE and spa-typing data from analysis of MRSA isolates from the many centers that have access to the relevant equipment can be compared to reference patterns/sequences, and clonal designations can be made. In the majority of cases, these will correspond to those made by the (more expensive) method of choice-MLST/SCCmec typing-and these alternative methods can therefore be used as frontline typing systems for multicenter surveillance of MRSA.”, “author” : { “dropping-particle” : “”, “family” : “Cookson”, “given” : “Barry D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Robinson”, “given” : “D. Ashley”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Monk”, “given” : “Alastair B.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Murchan”, “given” : “Stephen”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Deplano”, “given” : “Ariane”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ryck”, “given” : “Rafau00ebl”, “non-dropping-particle” : “De”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Struelens”, “given” : “Marc J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Scheel”, “given” : “Christina”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Fussing”, “given” : “Vivian”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Salmenlinna”, “given” : “Saara”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Vuopio-Varkila”, “given” : “Jaana”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Cuny”, “given” : “Christina”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Witte”, “given” : “Wolfgang”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tassios”, “given” : “Panayotis T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Legakis”, “given” : “Nikolas J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Leeuwen”, “given” : “Willem”, “non-dropping-particle” : “Van”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Belkum”, “given” : “Alex”, “non-dropping-particle” : “Van”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Vindel”, “given” : “Anna”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Garaizar”, “given” : “Javier”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Haeggman”, “given” : “Sara”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Olsson-Liljequist”, “given” : “Barbro”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ransjo”, “given” : “Ulrika”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Muller-Premru”, “given” : “Manica”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hryniewicz”, “given” : “Waleria”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Rossney”, “given” : “Angela”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “O’Connell”, “given” : “Brian”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Short”, “given” : “Benjamin D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Thomas”, “given” : “Jonathan”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “O’Hanlon”, “given” : “Simon”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Enright”, “given” : “Mark C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Clinical Microbiology”, “id” : “ITEM-2”, “issue” : “6”, “issued” : { “date-parts” : “2007” }, “page” : “1830-1837”, “title” : “Evaluation of molecular typing methods in characterizing a European collection of epidemic methicillin-resistant Staphylococcus aureus strains: The HARMONY collection”, “type” : “article-journal”, “volume” : “45” }, “uris” : “http://www.mendeley.com/documents/?uuid=6dc313cd-5363-48d0-9eb9-3d33b3ed99b4” } , “mendeley” : { “formattedCitation” : “(Cookson et al. 2007; K. Hiramatsu et al. 1997)”, “plainTextFormattedCitation” : “(Cookson et al. 2007; K. Hiramatsu et al. 1997)”, “previouslyFormattedCitation” : “(Cookson et al. 2007; K. Hiramatsu et al. 1997)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Cookson et al. 2007; K. Hiramatsu et al. 1997)
Genotyping methods:In fact, for the molecular typing of S. aureus, several typing methods have been developed. Most importantly for a typing method to be effective it should be inexpensive, have high discriminatory power, good reproducibility, and be easy to perform and interpret. Several molecular techniques have been developed for the typing of bacterial strains in the last decade including : arbitrarily primed polymerase chain reaction (AP-PCR), pulsed-field gel electrophoresis (PFGE), plasmid fingerprinting (PF), variable number tandem repeat analysis (VNTR) typing, multiple-locus variable-number tandem repeat analysis (MLVA), multilocus sequence typing (MLST) and SCCmec typing in the case of MRSA. All These techniques have been found mainly in research and reference laboratories but now a days are being used in advanced clinical laboratories ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “http://dx.doi.org/10.1590/S1413-86702003000100005”, “ISBN” : “1413-8670 (Print)\r1413-8670 (Linking)”, “ISSN” : “1413-8670”, “PMID” : “12807690”, “abstract” : “Staphylococcus aureus has long been recognised as an important pathogen in human disease. Serious staphylococcal infections can frequently occur in inpatients and may lead to dire consequences, especially for therapy with antimicrobial agents. The increase in the frequency of Methicillin-Resistant Staphylococcus aureus (MRSA) as the causal agent of nosocomial infection and the possibility of emergence of resistance to vancomycin demands a quick and trustworthy characterization of isolates and identification of clonal spread within hospitals. Enough information must be generated to permit the implementation of appropriate measures for control of infection, so that outbreaks can be contained. Molecular typing techniques reviewed in this manuscript include: plasmid profile analysis, analysis of chromosomal DNA after enzymatic restriction, Southern blotting, pulsed field gel electrophoresis (PFGE), techniques involving polymerase chain reaction and multilocus sequence typing (MLST). Repetitive DNA Sequence PCR (rep-PCR) may be used for screening due to its practicality, low cost and reproducibility. Because of its high discriminatory power Pulsed-Field Gel Electrophoresis (PFGE) still remains the gold standard for MRSA typing. New techniques with higher reproducibility and discriminatory power, such as Multi-Locus Sequence Typing (MLST), are appearing. These are mostly useful for global epidemiology studies. Molecular typing techniques are invaluable tools for the assessment of putative MRSA outbreaks and so should be extensively used for this purpose”, “author” : { “dropping-particle” : “”, “family” : “Trindade”, “given” : “P A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “McCulloch”, “given” : “J A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Oliveira”, “given” : “G A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Mamizuka”, “given” : “E M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Braz.J.Infect.Dis.”, “id” : “ITEM-1”, “issue” : “1413-8670 (Print)”, “issued” : { “date-parts” : “2003” }, “page” : “32-43”, “title” : “Molecular techniques for MRSA typing: current issues and perspectives”, “type” : “article-journal”, “volume” : “7” }, “uris” : “http://www.mendeley.com/documents/?uuid=7fa3f01c-e7e9-41e8-bb44-25629d84d7b8” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1128/JCM.41.4.1801-1804.2003”, “ISBN” : “0095-1137”, “ISSN” : “0095-1137”, “PMID” : “12682193”, “abstract” : “The PCR-based methodology applied to multiple-locus variable numbers of tandem repeat (VNTR) analysis was recently shown to be a useful technique for the molecular typing of clinical isolates of several bacterial species. We have adopted this method for the molecular typing of methicillin-resistant Staphylococcus aureus. Five staphylococcal VNTR loci (sdr, clfA, clfB, ssp, and spa) were subjected to analysis, and it was shown that the method allows typing of S. aureus strains with the discriminatory power and reproducibility of pulsed-field gel electrophoresis while at the same time being rapid and applicable to analysis of large numbers of isolates.”, “author” : { “dropping-particle” : “”, “family” : “Sabat”, “given” : “A.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Krzyszton-Russjan”, “given” : “J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Strzalka”, “given” : “W.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Filipek”, “given” : “R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kosowska”, “given” : “K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hryniewicz”, “given” : “W.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Travis”, “given” : “J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Potempa”, “given” : “J.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Clinical Microbiology”, “id” : “ITEM-2”, “issue” : “4”, “issued” : { “date-parts” : “2003” }, “page” : “1801-1804”, “title” : “New method for typing Staphylococcus aureus strains: multiple-locus variable-number tandem repeat analysis of polymorphism and genetic relationships of clinical isolates”, “type” : “article-journal”, “volume” : “41” }, “uris” : “http://www.mendeley.com/documents/?uuid=ba42a868-bc93-4b77-8e42-a4b7382c0c8a” } , “mendeley” : { “formattedCitation” : “(Sabat et al. 2003; Trindade et al. 2003)”, “plainTextFormattedCitation” : “(Sabat et al. 2003; Trindade et al. 2003)”, “previouslyFormattedCitation” : “(Sabat et al. 2003; Trindade et al. 2003)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Sabat et al. 2003; Trindade et al. 2003).

The whole genome sequencing is one of the most effective technology to revel information about the virulence of pathogens and its epidemiological spread in an outbreak ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1016/j.meegid.2013.04.030”, “ISBN” : “2122633255”, “ISSN” : “15671348”, “PMID” : “23648426”, “abstract” : “Staphylococcus aureus is a prominent cause of human infections globally. The high prevalence of infections is compounded by antibiotic resistance-a significant problem for treatment. Methicillin-resistant S. aureus (MRSA) is endemic in hospitals and healthcare facilities worldwide, and is an increasingly common cause of community-associated bacterial infections in industrialized countries. Although much focus is placed on the role of S. aureus as a human pathogen, it is in fact a human commensal organism that has had a relatively long coexistence with the human host. Many S. aureus infections can be explained by host susceptibility or other predisposing risk factors. On the other hand, the emergence/re-emergence of successful S. aureus clones (referred to as epidemic waves) suggests a rapid bacterial adaption and evolution, which includes the emergence of antibiotic resistance and increased virulence and/or transmissibility. It is within this context that we review our understanding of selected S. aureus epidemic waves, and highlight the use of genome sequencing as a means to better understand the evolution of each lineage. u00a9 2013 The Authors.”, “author” : { “dropping-particle” : “”, “family” : “Uhlemann”, “given” : “Anne Catrin”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Otto”, “given” : “Michael”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Lowy”, “given” : “Franklin D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “DeLeo”, “given” : “Frank R.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Infection, Genetics and Evolution”, “id” : “ITEM-1”, “issued” : { “date-parts” : “2014” }, “page” : “563-574”, “title” : “Evolution of community- and healthcare-associated methicillin-resistant Staphylococcus aureus”, “type” : “article-journal”, “volume” : “21” }, “uris” : “http://www.mendeley.com/documents/?uuid=b93dec4f-bf32-4c89-9462-9b31b17c98d2” } , “mendeley” : { “formattedCitation” : “(Uhlemann et al. 2014)”, “plainTextFormattedCitation” : “(Uhlemann et al. 2014)”, “previouslyFormattedCitation” : “(Uhlemann et al. 2014)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Uhlemann et al. 2014), as well its molecular changes that enable the spread of the infection from one to another and its expensive.

In fact, to well understand the epidemiology of nosocomial pathogens such as MRSA, molecular methods have been applied aiming to control the incidence of MRSA thorough developing a knowledge of its epidemiology and molecular typing techniques which ideally suited for this purpose because they are not phenotype-dependent ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1111/j.1469-0691.2006.01573.x”, “ISBN” : “0095-1137 (Print)\n0095-1137 (Linking)”, “ISSN” : “1198-743X”, “PMID” : “17391376”, “abstract” : “Staphylococcus aureus is a potentially pathogenic bacterium that causes a broad spectrum of diseases. S. aureus can adapt rapidly to the selective pressure of antibiotics, and this has resulted in the emergence and spread of methicillin-resistant S. aureus (MRSA). Resistance to methicillin and other beta-lactam antibiotics is caused by the mecA gene, which is situated on a mobile genetic element, the Staphylococcal Cassette Chromosome mec (SCCmec). To date, five SCCmec types (I-V) have been distinguished, and several variants of these SCCmec types have been described. All SCCmec elements carry genes for resistance to beta-lactam antibiotics, as well as genes for the regulation of expression of mecA. Additionally, SCCmec types II and III carry non-beta-lactam antibiotic resistance genes on integrated plasmids and a transposon. The epidemiology of MRSA has been investigated by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), spa typing and SCCmec typing. Numerous MRSA clones have emerged and disseminated worldwide. SCCmec has been acquired on at least 20 occasions by different lineages of methicillin-sensitive S. aureus. Although most MRSA strains are hospital-acquired (HA-MRSA), community-acquired MRSA (CA-MRSA) strains have now been recognised. CA-MRSA is both phenotypically and genotypically different from HA-MRSA. CA-MRSA harbours SCCmec types IV or V, and is associated with the genes encoding Panton-Valentine leukocidin. The prevalence of MRSA ranges from 0.6% in The Netherlands to 66.8% in Japan. This review describes the latest developments in knowledge concerning the structure of SCCmec, the molecular evolution of MRSA, the methods used to investigate the epidemiology of MRSA, and the risk-factors associated with CA-MRSA and HA-MRSA.”, “author” : { “dropping-particle” : “”, “family” : “Deurenberg”, “given” : “R H”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Vink”, “given” : “C”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Kalenic”, “given” : “S”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Friedrich”, “given” : “A W”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Bruggeman”, “given” : “C A”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Stobberingh”, “given” : “E E”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2007” }, “page” : “222-235”, “title” : “The molecular evolution of methicillin-resistant Staphylococcus aureus.”, “type” : “article-journal”, “volume” : “13” }, “uris” : “http://www.mendeley.com/documents/?uuid=979191da-6ad3-4e0e-8be7-143edd4ae2da” } , “mendeley” : { “formattedCitation” : “(Deurenberg et al. 2007)”, “plainTextFormattedCitation” : “(Deurenberg et al. 2007)”, “previouslyFormattedCitation” : “(Deurenberg et al. 2007)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(Deurenberg et al. 2007)
Antimicrobial susceptibility pattern:The susceptibility of a bacterium to unique antibiotics can be used to evaluate and differentiate MRSA strains. Cheapness and its potential for use routinely in many medical laboratories consider the main advantage of this method. In contrast , antimicrobial susceptibility styles (antibiograms) have low discriminatory power and reproducibility and are affected from environmental factors. Moreover, the obtaining or loss of resistance plasmids way that unrelated strains can deliver comparable antibiograms whilst genetically related lines can gave a different antibiograms ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1093/jac/40.1.135”, “ISBN” : “0305-7453 (Print)\r0305-7453 (Linking)”, “ISSN” : “03057453”, “PMID” : “13545234”, “abstract” : “Objective: To study markers of progression in a cohort of HIV-infected intravenous drug users (IDU). Design: A prospective epidemiologic study. Setting and patients. We studied progression of HIV infection among 126 IDU attending the Municipal Health Service in Amsterdam. Main outcome measures: Progression was defined as a decline of the CD4 cell count to 30 years relative hazard (RH), 7.7 95% confidence intervals (CI), 1.7-36.0, core antibody negativity RH, 5.3 (95% Cl, 1.6-17.6), CD4 cell count for CD4 cells 350-500 x 10(6)/l, RH, 1.38 (95% Cl, 0.37-5.16); for CD4 cells 200-350 x 10(6)/l, RH, 9.20 (95% Cl, 2.73-31.05) compared with a CD4 count > 500 x 10(6)/l. A lower rate of progression was associated with borrowing used injecting equipment. IDU who reported borrowing injecting equipment between 1980 and baseline 10-99 times or >99 times had a RH of 0.44 (95% Cl, 0.22-0.88) and 0.19 (95% Cl, 0.03-0.37), respectively, compared with IDU who had borrowed <10 times. p24 antigen positivity was more predictive than core antibody negativity in a model with time-dependent variables, the relative risk for p24 antigen-positive participants was 3.5 (95% Cl, 1.3-9.3). Additional analysis of progression to AIDS in a larger group of IDU showed comparable results with regard to the effect of borrowing on progression. Conclusions: Our observation that those IDU who reported borrowing injecting equipment most frequently appeared to have the lowest rate of progression, corrected for some sources of potential confounding, requires further epidemiologic confirmation and extended laboratory studies since other sources of bias might have been present. Baseline CD4 count, age and core antibody or p24 antigen were predictive of progression in IDU. We wish to emphasize that our results do not imply that borrowing should be encouraged, but may have implications for our understanding of HIV pathogenesis.”, “author” : { “dropping-particle” : “”, “family” : “Hiramatsu”, “given” : “K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Hanaki”, “given” : “H.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Ino”, “given” : “T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Yabuta”, “given” : “K.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Oguri”, “given” : “T.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Tenover”, “given” : “F. C.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “Journal of Antimicrobial Chemotherapy”, “id” : “ITEM-1”, “issue” : “1”, “issued” : { “date-parts” : “1997” }, “page” : “135-136”, “title” : “Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility 1”, “type” : “article”, “volume” : “40” }, “uris” : “http://www.mendeley.com/documents/?uuid=07357655-673a-471b-8bb5-c5ce18b2e43d” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1053/jhin.1999.0701”, “ISSN” : “0195-6701”, “PMID” : “10706798”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) has spread to all parts of the world. Effective control measures are dependent on a thorough knowledge of the organism’s epidemiology which requires a typing technique that can be universally applied. Many typing methods have been developed for MRSA but none has been adopted as the internationally recognized standard. This review summarizes the information available on each in order to assess their suitability as a reference procedure. The majority of phenotypic and genotypic techniques are not sufficiently discriminatory, reproducible, stable or useful in an outbreak to be acceptable. The methods which do fulfil these requirements and have a potential for standardization, such as pulsed-field gel electrophoresis, binary typing or a combination of more rapid techniques, require further systematic evaluation.”, “author” : { “dropping-particle” : “”, “family” : “Weller”, “given” : “T M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Journal of hospital infection”, “id” : “ITEM-2”, “issue” : “3”, “issued” : { “date-parts” : “2000” }, “page” : “160-172”, “title” : “Methicillin-resistant Staphylococcus aureus typing methods: which should be the international standard?”, “type” : “article-journal”, “volume” : “44” }, “uris” : “http://www.mendeley.com/documents/?uuid=9e54afcf-6b80-43ae-b023-366770517994” } , “mendeley” : { “formattedCitation” : “(K. Hiramatsu et al. 1997; Weller 2000)”, “plainTextFormattedCitation” : “(K. Hiramatsu et al. 1997; Weller 2000)”, “previouslyFormattedCitation” : “(K. Hiramatsu et al. 1997; Weller 2000)” }, “properties” : { “noteIndex” : 0 }, “schema” : “https://github.com/citation-style-language/schema/raw/master/csl-citation.json” }(K. Hiramatsu et al. 1997; Weller 2000). However, antimicrobial susceptibility patterns consider unreliable as a distinguishing typing method and neither the antibiograms of an epidemic or endemic clone can be useful for monitoring and treatment purposes ADDIN CSL_CITATION { “citationItems” : { “id” : “ITEM-1”, “itemData” : { “DOI” : “10.1053/jhin.1999.0701”, “ISSN” : “0195-6701”, “PMID” : “10706798”, “abstract” : “Methicillin-resistant Staphylococcus aureus (MRSA) has spread to all parts of the world. Effective control measures are dependent on a thorough knowledge of the organism’s epidemiology which requires a typing technique that can be universally applied. Many typing methods have been developed for MRSA but none has been adopted as the internationally recognized standard. This review summarizes the information available on each in order to assess their suitability as a reference procedure. The majority of phenotypic and genotypic techniques are not sufficiently discriminatory, reproducible, stable or useful in an outbreak to be acceptable. The methods which do fulfil these requirements and have a potential for standardization, such as pulsed-field gel electrophoresis, binary typing or a combination of more rapid techniques, require further systematic evaluation.”, “author” : { “dropping-particle” : “”, “family” : “Weller”, “given” : “T M”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” } , “container-title” : “The Journal of hospital infection”, “id” : “ITEM-1”, “issue” : “3”, “issued” : { “date-parts” : “2000” }, “page” : “160-172”, “title” : “Methicillin-resistant Staphylococcus aureus typing methods: which should be the international standard?”, “type” : “article-journal”, “volume” : “44” }, “uris” : “http://www.mendeley.com/documents/?uuid=9e54afcf-6b80-43ae-b023-366770517994” }, { “id” : “ITEM-2”, “itemData” : { “DOI” : “10.1128/JCM.02402-06”, “ISBN” : “0095-1137 (Print)\r0095-1137 (Linking)”, “ISSN” : “00951137”, “PMID” : “17428929”, “abstract” : “We analyzed a representative sample of methicillin-resistant Staphylococcus aureus (MRSA) from 11 European countries (referred to as the HARMONY collection) using three molecular typing methods used within the HARMONY group to examine their usefulness for large, multicenter MRSA surveillance networks that use these different laboratory methodologies. MRSA isolates were collected based on their prevalence in each center and their genetic diversity, assessed by pulsed-field gel electrophoresis (PFGE). PFGE groupings (< or = 3 bands difference between patterns) were compared to those made by sequencing of the variable repeats in the protein A gene spa and clonal designations based on multilocus sequence typing (MLST), combined with PCR analysis of the staphylococcal chromosome cassette containing the mec genes involved in methicillin resistance (SCCmec). A high level of discrimination was achieved using each of the three methodologies, with discriminatory indices between 89.5% and 91.9% with overlapping 95% confidence intervals. There was also a high level of concordance of groupings made using each method. MLST/SCCmec typing distinguished 10 groups containing at least two isolates, and these correspond to the majority of nosocomial MRSA clones described in the literature. PFGE and spa typing resolved 34 and 31 subtypes, respectively, within these 10 MRSA clones, with each subtype differing only slightly from the most common pattern using each method. The HARMONY group has found that the methods used in this study differ in their availability and affordability to European centers involved in MRSA surveillance. Here, we demonstrate that the integration of such technologies is achievable, although common protocols (such as we have developed for PFGE) may also be important, as is the use of centralized Internet sites to facilitate data analysis. PFGE and spa-typing data from analysis of MRSA isolates from the many centers that have access to the relevant equipment can be compared to reference patterns/sequences, and clonal designations can be made. In the majority of cases, these will correspond to those made by the (more expensive) method of choice-MLST/SCCmec typing-and these alternative methods can therefore be used as frontline typing systems for multicenter surveillance of MRSA.”, “author” : { “dropping-particle” : “”, “family” : “Cookson”, “given” : “Barry D.”, “non-dropping-particle” : “”, “parse-names” : false, “suffix” : “” }, { “dropping-particle” : “”, “family” : “Robinson”, “given” : “D. 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Many different protocols have been developed in laboratories that have extensive experience with the technique and have established national databases. However, the comparabilities of the different European PFGE protocols for MRSA and of the various national MRSA clones themselves had not been addressed until now. This multinational European Union (EU) project has established for the first time a European database of representative epidemic MRSA (EMRSA) strains and has compared them by using a new “harmonized” PFGE protocol developed by a consensus approach that has demonstrated sufficient reproducibility to allow the successful comparison of pulsed-field gels between laboratories and the tracking of strains around the EU. In-house protocols from 10 laboratories in eight European countries were compared by each center with a “gold standard” or initial harmonized protocol in which many of the parameters had been standardized. The group found that it was not important to standardize some elements of the protocol, such as the type of agarose, DNA block preparation, and plug digestion. Other elements were shown to be critical, namely, a standard gel volume and concentration of agarose, the DNA concentration in the plug, the ionic strength and volume of running buffer used, the running temperature, the voltage, and the switching times of electrophoresis. A new harmonized protocol was agreed on, further modified in a pilot study in two laboratories, and finally tested by all others. Seven laboratories’ gels were found to be of sufficiently good quality to allow comparison of the strains by using a computer software program, while two gels could not be analyzed because of inadequate destaining and DNA overloading. Good-quality gels and inclusion of an internal quality control strain are essential before attempting intercenter PFGE comparisons. A number of clonally related strains have been shown to be present in multiple countries throughout Europe. The well-known Iberian clone has been demonstrated in Belgium, Finland, France, Germany, and Spain (and from the wider HARMONY collection in Portugal, Slovenia, and Sweden). Strains from the United Kingdom (EMRSA-15 and -16) have been identified in several othercountries, and other clonally related strains have also been identified. 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Appendix A
Chapter tow
General Material and Methods:Chemical and Reagents:
The chemical and reagents that were used in this study are listed in Appendix A with their suppliers.
Preparation of buffers and solutions :Buffers and solutions are described in details in Appendix A.
Chelex preparation:
To prepare 5 % chelex to use it for the DNA extraction at the Sma I Multilplex PCR, we measure 2.5g of chelex and add it to falcon tube contain 50ml sterile distilled water. Vortex to make sure it mixes well.

TAE buffer preparation for gel electrophoresis:
TAE buffer 50 X preparation:
Measure the following ingredients : 242g Tris free base, 18.61g Disodium EDTA.
Add the previous measured ingredients to 700ml sterile distilled water.
Stir until dissolved then add 57.1ml Glacial Acetic Acid and adjust the volume to 1 Liter with sterile distilled water.

Stored at room temperature (25 C).

TAE buffer 1 X preparation:
Measure 294ml from sterile distilled water.

Measure 6ml from 50X TAE buffer and add it to the measured distilled water.

Mix well and it ready to use.

Stored at room temperature (25 C).

Culture Medium:
Chromagar MRSA medium been ordered from the ( Saudi Prepared Media Laboratory Company LTD). The catalog number is 1031 for this item based on company profile. This Culture medium were used this study will be described in details in Appendix A.

Growth and storage of strains:Sources of standard staphylococci strains:The standard S. aureus strains and two S. epidermidis strains used in these studies were obtained from known ATCC samples.
Sources of Nasal swab isolates:
A total of 483 nasal swab were collected from four different malls based on its geographical location in Jeddah city to cover the parameter of the city. Amies transport medium swab were used to collect the samples from the participant after meeting the inclusion criteria of our study which will be listed in the coming section.

Inclusion and exclusion criteria:
The inclusion criteria of our study are listed as:
Adult ( 18 – 65 years old)
Jeddah Resident
Did not have any infection in the last three months.
Did not use any antibiotics drugs for the last month.
Not been hospitalized at the last three months.

Don’t live with first degree relative that is working in medical field.
Not a health care worker or working in health care facilities.

However, who never meet up with the inclusion criteria was excluded from the study and no samples were collected from them.

Sample collection methods:
To collect the samples for our research we apply for an authorization approval letter from the Highness governor of Jeddah City Prince Meshal Bin Majed Al Saud. Upon his Highness approval letter, we coverage four big mall in Jeddah city that was selected based on the geographical location to cover the areas from all geographical directions. The mall is listed as following:
Red Sea Mall ( North side area)
Sultan Mall ( West side area)
Al Salam Mall ( South side area)
Al Yasmine Mall ( East side area)
In each mall, there was a group contain eight students from the college of medical laboratory technology, four males and four females, supervised by doctor of faculty member. The last group was supervised by myself as major researcher of this research.
Amie’s transport medium were used to collect the samples from all participants nasal cavity. The procedure of the samples collection is simply to insert the swab to the nasal cavity for about 2cm and rotate it five times attaching the cavity wall to collect the samples from both cavity. The sample collection procedure was though and demonstrated to all the students who help us in collecting the samples.

Identification of MRSA from collected samples:Chromogenic Agar MRSA Screening:All samples that were collected were cultured on the same day on Chromogenic MRSA Agar, incubated over night at 37 C and check for growth on the next day. Based on factory recommendation that all pink colony consider as MRSA while other colors such as blue or white not consider as MRSA.
Subculture on Blood Agar and Glycerol:
After the overnight incubation, all the isolates been checked for growth and whatever give pink to purple color been subculture on blood agar and glycerol. Blood cultured agar plates incubated at 37 C over night to be used later for the identification and DNA extraction, while the samples in glycerol been stored at – 80 C for back up.

Latex slide agglutination Coagulase Screening Test:
We did screen all positive samples from the Chromogenic MRSA agar with latex slide agglutination coagulase test. procedure as below list:
Mix the latex reagent by shaking; expel any latex from the dropper for complete mixing.
Dispense 1 drop of Test Latex onto one of the circles on the reaction card and add 1 drop of Control Latex onto another circle.
Using a microbiological loop pick up and smear colonies onto the Test Latex-containing circle and mix this into the Test Latex reagent. Spread to cover the circle.

Repeat step 3 for the Control Latex.
Pick up and hand rock the card for up to 20 sec and observe for agglutination under normal lighting conditions. Read macroscopically.

Dispose of the reaction card in an appropriate biohazard container.
Re-cap the bottles and return to the refrigerator.
Agglutination means sample is coagulase positive.

Extraction of chromosomal DNA from MRSA:
2.7.4.1 Rapid Extraction of chromosomal DNA using the boiling method for conventional Polymerase Chain Reaction (PCR):
The DNA extraction procedure was done as the following step:
Sterile Eppendorf tubes is labeled with the sample code.

30 l of sterile distilled water added to each tube.

1-3 colony from the subculture isolates been added to the tube.

Vortex all tubes and then quick spin it.

All tube been placed in heat block for 10 min at 95 C.

Centrifuge the samples at 13000 rpm for 5 minutes.
Sample is ready to use for conventional PCR.

2.7.4.2 Extraction of chromosomal DNA from MRSA for Sma I Multilplex PCR:
The DNA extraction procedure was done as the following step:
Sterile Eppendorf tubes is labeled with the sample code.

200 l of 5 % chelex added to each tube.

2-5 colony of the subculture isolates been added to the tube.

Vortex all tubes and then quick spin it.

All tube been placed in heat block for 10 min at 95 C.

Centrifuge the samples at 13000 rpm for 5 minutes.
Sample is ready to use for Sma I Multilplex PCR.

Molecular typing of MRSA isolates:
Polymerase Chain Reaction ( PCR):In order to amplify regions of the DNA the PCR technique was used. Oligonucleotide primers for amplifying specific MRSA genes were designed according to the following parameters: G/C between 50-60%, the 3′-end had a G or C and more three adjacent nucleotide repeats (e.g. AAAA or TTTT) were avoided.
At this part of the study we apply three different single plex PCR experiment targeting different genes concern MRSA. These reactions applied for only the positive isolate from the chromogenic MRSA agar and been divided as the following:
Coa PCR : targeting the Coa gene that confirm our finding if the isolate is S.aureus or not.

MecA PCR: targeting the mecA gene to confirm our finding if the isolates is consider as MRSA or not.
PVL PCR: targeting the PVL gene to confirm our finding with CA-MRSA, while this gene is present in only 2% of the CA-MRSA.

Each one of these experiments were done separately as single plex PCR experiment targeting one gene at time for all positive isolates. PCR reactions were performed as indicated in Table 3 and according to the reaction conditions in Table 4 .The sequences of primers used in this study are listed in Table 5.

Components Volume per 25 l reaction (l)
DNA polymerase Buffer 2.5
BSA 2
MgCl2 1.5
dNTP 1
Coa Forward Primer 0.75
Coa Reverse Primer 0.75
Taq polymerase 0.25
Milli-Q water 14.25
Templets DNA 2
Table SEQ Table * ARABIC 3: Table 3: Components of PCR reaction Mixture
Genes
Steps
Coa mecA PVL
C Min Cycle C Min Cycle C Min Cycle
Denaturation 96 2 1 96 2 1 96 2 1
Denaturation 96 0.4 96 0.4 96 0.4 Annealing 56 0.4 -179070-2444750035 56 0.4 -179070-2444750035 56 0.4 -179070-2444750035
Extension 72 0.4 72 0.4 72 0.4 Final Extension 72 2 1 72 2 1 72 2 1
Table SEQ Table * ARABIC 4: PCR reaction Conditions2.8.2. Detection of the mecA methicillin-resistance gene:S.aureus ATCC control were used as a mecA positive control and S.epidermidis ATCC control as a mecA negative control. The primer pairs designed by Murakami et al. (1991) were used to amplify a 532-bp region of mecA. The PCR reaction was performed as in Table 3 according to reaction condition in Table 4
2.8.3. Detection of coagulase (coa) gene:The presence of the coa gene was determined using the primers of Walker et al. (1998). These primers were used to amplify an 830bp region of the coa gene according to the PCR reaction and condition in Table 3 and Table 4. DNA for S. aureus NCTC 6571 was used as a coa positive control and S. epidermidis was used as a coa negative control.
2.8.4. Detection of the Panton-Valentin leukocidin (lukS-PV) gene:De novo primers were designed to target a 443bp region of the lukS-PV gene. The sequences of this gene were acquired from the National Centre for Biotechnology Information (NCBI) database. The PCR reaction was performed as in Table 3 according to reaction condition in Table 4 , PVL- MRSA strains were used as controls.

Pulse field gel Electrophoresis :For the single plex gene detection we used an amount of about 5-10 ?l of PCR product was mixed with loading dye buffer and loaded on 2% agarose gel containing ethidium bromide (0.5?g/ml). Electrophoresis carried out in 1X TAE buffer at 100 V for 50-60 min. PCR products were sized against molecular marker ladder (100bp-1kb), their bands visualized under UV-light and documented using a gel documentation system.

Sma I Multilplex PCR:Multiplex PCR was performed in a reaction mixture volume of 25 l, containing 2.5l DNA polymerase buffer, 1 l dNTP, 1.5 l MgCl2, 2 bovine serum albumin (BSA), 0.5 M concentrations of primers except mecA primers, which were 1M, 0.5 l of 5 U/l Taq polymerase (Qiagen), and 3 l of DNA template. The reaction conditions were as follows: initial denaturation for 2 min at 96°C, followed by 35 cycles of 96°C for 40 s, 56°C for 40 s, and 72°C for 40 s, with a final extension at 72°C for 2 min. The resulting amplicons were separated on 3% pulse field agarose gel (LMP; BioGene, United Kingdom) in 1 x TAE at 100 V for 3 h and stained after the running time is done for 30 minutes in 0.5 g/ml ethidium bromide which made by adding 35 l of ethidium bromide to 700 ml of 1X TAE buffer that stored at 4 C. gel been washer with distilled water prior visualizing it under UV-light and documented using a gel documentation system. PCR products were sized against molecular marker ladder (50bp-1kb).

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