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      Methicillin-Resistant Staphylococcus aureus: Molecular Characterization, Evolution, and Epidemiology

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      Clinical Microbiology Reviews
      American Society for Microbiology

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          SUMMARY

          Staphylococcus aureus, a major human pathogen, has a collection of virulence factors and the ability to acquire resistance to most antibiotics. This ability is further augmented by constant emergence of new clones, making S. aureus a “superbug.” Clinical use of methicillin has led to the appearance of methicillin-resistant S. aureus (MRSA). The past few decades have witnessed the existence of new MRSA clones. Unlike traditional MRSA residing in hospitals, the new clones can invade community settings and infect people without predisposing risk factors. This evolution continues with the buildup of the MRSA reservoir in companion and food animals. This review focuses on imparting a better understanding of MRSA evolution and its molecular characterization and epidemiology. We first describe the origin of MRSA, with emphasis on the diverse nature of staphylococcal cassette chromosome mec (SCC mec). mecA and its new homologues ( mecB, mecC, and mecD), SCC mec types (13 SCC mec types have been discovered to date), and their classification criteria are discussed. The review then describes various typing methods applied to study the molecular epidemiology and evolutionary nature of MRSA. Starting with the historical methods and continuing to the advanced whole-genome approaches, typing of collections of MRSA has shed light on the origin, spread, and evolutionary pathways of MRSA clones.

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          Invasive methicillin-resistant Staphylococcus aureus infections in the United States.

          As the epidemiology of infections with methicillin-resistant Staphylococcus aureus (MRSA) changes, accurate information on the scope and magnitude of MRSA infections in the US population is needed. To describe the incidence and distribution of invasive MRSA disease in 9 US communities and to estimate the burden of invasive MRSA infections in the United States in 2005. Active, population-based surveillance for invasive MRSA in 9 sites participating in the Active Bacterial Core surveillance (ABCs)/Emerging Infections Program Network from July 2004 through December 2005. Reports of MRSA were investigated and classified as either health care-associated (either hospital-onset or community-onset) or community-associated (patients without established health care risk factors for MRSA). Incidence rates and estimated number of invasive MRSA infections and in-hospital deaths among patients with MRSA in the United States in 2005; interval estimates of incidence excluding 1 site that appeared to be an outlier with the highest incidence; molecular characterization of infecting strains. There were 8987 observed cases of invasive MRSA reported during the surveillance period. Most MRSA infections were health care-associated: 5250 (58.4%) were community-onset infections, 2389 (26.6%) were hospital-onset infections; 1234 (13.7%) were community-associated infections, and 114 (1.3%) could not be classified. In 2005, the standardized incidence rate of invasive MRSA was 31.8 per 100,000 (interval estimate, 24.4-35.2). Incidence rates were highest among persons 65 years and older (127.7 per 100,000; interval estimate, 92.6-156.9), blacks (66.5 per 100,000; interval estimate, 43.5-63.1), and males (37.5 per 100,000; interval estimate, 26.8-39.5). There were 1598 in-hospital deaths among patients with MRSA infection during the surveillance period. In 2005, the standardized mortality rate was 6.3 per 100,000 (interval estimate, 3.3-7.5). Molecular testing identified strains historically associated with community-associated disease outbreaks recovered from cultures in both hospital-onset and community-onset health care-associated infections in all surveillance areas. Invasive MRSA infection affects certain populations disproportionately. It is a major public health problem primarily related to health care but no longer confined to intensive care units, acute care hospitals, or any health care institution.
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            Waves of resistance: Staphylococcus aureus in the antibiotic era.

            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.
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              eBURST: inferring patterns of evolutionary descent among clusters of related bacterial genotypes from multilocus sequence typing data.

              The introduction of multilocus sequence typing (MLST) for the precise characterization of isolates of bacterial pathogens has had a marked impact on both routine epidemiological surveillance and microbial population biology. In both fields, a key prerequisite for exploiting this resource is the ability to discern the relatedness and patterns of evolutionary descent among isolates with similar genotypes. Traditional clustering techniques, such as dendrograms, provide a very poor representation of recent evolutionary events, as they attempt to reconstruct relationships in the absence of a realistic model of the way in which bacterial clones emerge and diversify to form clonal complexes. An increasingly popular approach, called BURST, has been used as an alternative, but present implementations are unable to cope with very large data sets and offer crude graphical outputs. Here we present a new implementation of this algorithm, eBURST, which divides an MLST data set of any size into groups of related isolates and clonal complexes, predicts the founding (ancestral) genotype of each clonal complex, and computes the bootstrap support for the assignment. The most parsimonious patterns of descent of all isolates in each clonal complex from the predicted founder(s) are then displayed. The advantages of eBURST for exploring patterns of evolutionary descent are demonstrated with a number of examples, including the simple Spain(23F)-1 clonal complex of Streptococcus pneumoniae, "population snapshots" of the entire S. pneumoniae and Staphylococcus aureus MLST databases, and the more complicated clonal complexes observed for Campylobacter jejuni and Neisseria meningitidis.
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                Author and article information

                Journal
                Clinical Microbiology Reviews
                Clin Microbiol Reviews
                American Society for Microbiology
                0893-8512
                1098-6618
                October 2018
                September 12 2018
                : 31
                : 4
                Article
                10.1128/CMR.00020-18
                6148192
                30209034
                9eb28bdc-dccd-496f-8a48-c0c0f020fb07
                © 2018
                Product
                Self URI (article page): http://cmr.asm.org/lookup/doi/10.1128/CMR.00020-18

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