Global epidemiology of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA)

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During the 1990s, various reports of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections appeared in the literature, caused by novel strains genetically distinct from traditional healthcare-associated MRSA (HA-MRSA). Numerous lineages of CA-MRSA have since emerged on every continent, several of which have spread internationally, most notably USA300. CA-MRSA strains are increasingly implicated in nosocomial infections, and may eventually displace HA-MRSA strains in hospitals. Consequently, distinctions based on clinical epidemiology and susceptibility are becoming less relevant, arguing in favor of genotypic definitions. We review the current molecular epidemiology of CA-MRSA with respect to genetic diversity, global distribution, and factors related to its emergence and spread.

Highlights

► Numerous CA-MRSA lineages have been described in the last two decades. ► Several of these may be considered pandemic, particularly USA300. ► We highlight the molecular epidemiology of CA-MRSA clones at the present time. ► The close association between CA-MRSA and PVL remains controversial. ► CA-MRSA clones are increasingly causing healthcare-associated infections worldwide.

Introduction

Methicillin resistance in staphylococci is associated with acquisition of a large transmissible element known as staphylococcal cassette chromosome mec (SCCmec), an event that occurred in Staphylococcus aureus prior to the isolation of the first methicillin-resistant S. aureus (MRSA) strain in 1961 [1]. For most of the half-century following this watershed event, MRSA was considered to be a nosocomial pathogen, with a limited number of clonal backgrounds causing serious infections in individuals with healthcare-associated risk factors [2]. During the 1990s, however, reports of de novo community-associated MRSA (CA-MRSA) infections among healthy individuals began to appear in the literature, and were soon shown to be associated with genetically distinct lineages of MRSA, apparently unrelated to existing healthcare-associated MRSA (HA-MRSA) strains [3]. Soon thereafter, numerous lineages of CA-MRSA emerged on every continent [4••, 5••, 6••].

CA-MRSA strains are increasingly implicated in nosocomial infections [7], and mathematical models predict that they will ultimately displace traditional HA-MRSA strains in healthcare settings [8, 9]. Moreover, antimicrobial resistance is steadily increasing in certain lineages [10], which are likewise implicated in a widening spectrum of invasive disease [4••, 11]. Consequently, traditional distinctions between HA-MRSA and CA-MRSA based on clinical epidemiology and susceptibility are becoming increasingly less relevant [4••, 12], leading some authors to argue in favor of genotypic-based definitions for CA-MRSA [13]. Given the multiplicity of CA-MRSA strains which continue to emerge, this review will focus on the current molecular epidemiology of CA-MRSA.

Section snippets

Molecular typing of Staphylococcus aureus

An understanding of molecular typing methods for S. aureus is necessary to appreciate the nomenclature currently used to describe distinct clonal groups. At the present time, there are four primary methods in use internationally, including pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), spa typing, and SCCmec typing for MRSA [14, 15]. The first two methods have been developed for numerous bacterial and fungal species, while the latter two are specific to

Origins and emergence of CA-MRSA

In 1999, following a report describing four pediatric fatalities in the midwestern United States, CA-MRSA was recognized as a distinct clinical entity [17]. Before that, putative CA-MRSA cases were associated with intravenous drug users in Detroit, Michigan, and aboriginal populations in Western Australia [5••, 17]. Both the Australian (WA-1) and the U.S. (MW2) strains were subsequently classified as MLST clonal complex (CC) 1. Beginning in 2000, further outbreaks of CA-MRSA infections were

Molecular epidemiology of CA-MRSA

Currently, worldwide reports of CA-MRSA are associated with >20 distinct genetic lineages (Figure 1, Table 1, Table 2), five of which are globally predominant, including ST1-IV (WA-1, USA400), ST8-IV (USA300), ST30-IV (South West Pacific clone), ST59-V (Taiwan clone), and ST80-IV (European clone) [5••, 6••, 22•]. Among the latter, ST8-IV and ST30-IV may be considered pandemic, as they have been isolated repeatedly from every continent [6••, 23••]. ST8-IV is primarily associated with the global

USA300

Most reports of CA-MRSA involve USA300, currently the most prevalent MRSA strain in the U.S., and the only CA-MRSA strain thus far which appears to pose a global epidemic threat [16•, 40•]. The earliest known cases of USA300 were associated with a collegiate football team in Pennsylvania, followed by several outbreaks among prisoners in Mississippi and Los Angeles [11], and some authors speculate that the prevalence of incarceration in the U.S. may be amplifying the epidemic spread of USA300 [

Panton-Valentine leukocidin (PVL)

The potential role of the bacteriophage-encoded PVL toxin in CA-MRSA pathogenesis remains a matter of significant controversy, as reviewed extensively elsewhere [5••, 6••, 20]. The epidemiologic association between PVL and CA-MRSA is nevertheless striking [19], insofar as it is harbored by nearly every major CA-MRSA lineage [27], but found infrequently (<5%) in HA-MRSA and MSSA [3, 20]. It is also conspicuously absent from certain CA-MRSA lineages such as WA-1 (ST1-IV) [3, 23••], and its

Conclusion

The simultaneous global emergence of genetically divergent CA-MRSA strains rivals the earlier spread of intercontinental HA-MRSA lineages, and highlights the evolutionary versatility of MRSA as a pathogen no longer limited to healthcare environments [2, 3]. A recent study suggests that higher levels of methicillin resistance in HA-MRSA strains may suppress expression of virulence factors, thereby limiting their ability to compete with CA-MRSA strains in community settings [53]. Moreover,

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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