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Community-associated meticillin-resistant Staphylococcus aureus: the case for a genotypic definition

  • J.A. Otter
    Correspondence
    Corresponding author. Address: Directorate of Infection, 5th Floor, North Wing, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK. Tel.: +44 (0) 207 188 3127; fax: +44 (0) 207 928 0730.
    Affiliations
    Centre for Clinical Infection and Diagnostic Research (CIDR), Department of Infections Diseases, King's College London School of Medicine and Guy's and St. Thomas' NHS Foundation Trust, London, UK
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  • G.L. French
    Affiliations
    Centre for Clinical Infection and Diagnostic Research (CIDR), Department of Infections Diseases, King's College London School of Medicine and Guy's and St. Thomas' NHS Foundation Trust, London, UK
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      Summary

      Background

      New distinct strains of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) have emerged as a cause of infection in previously healthy individuals in community settings. It is important to identify CA-MRSA for clinical management, epidemiological analysis, infection prevention and control, and regulatory reporting, but definitions and nomenclature of these strains are confused.

      Aim

      To review attempts to define CA-MRSA and propose a new definition.

      Methods

      Non-systematic review.

      Findings

      Epidemiological definitions were useful for differentiating CA-MRSA and healthcare-associated (HA)-MRSA strain types in the past. However, although HA-MRSA strain types are rarely transmitted in the community, CA-MRSA strains have started to be transmitted in healthcare facilities, so epidemiological definitions are breaking down. CA-MRSA are community strains of S. aureus that have acquired the meticillin resistance gene, mecA. They are distinct from HA-MRSA and should be defined genetically. This may be done by combining genotypic typing by multi-locus sequence or spa with analysis of the staphylococcal cassette chromosome mec. Carriage of Panton-Valentine leukocidin or antimicrobial susceptibility profiles can be useful indicators of CA-MRSA but should not be used for their definition.

      Conclusion

      For full assessment of their epidemiology, MRSA infections should be characterized as: (1) caused by HA- or CA-MRSA strain types; (2) acquired in community or healthcare settings; and (3) onset in the community or healthcare facility.

      Introduction

      The great majority of infections with meticillin-resistant Staphylococcus aureus (MRSA) have occurred as a result of cross-infection in hospitals and other healthcare facilities. Only a limited number of clonal lineages of MRSA have been involved, and these healthcare-associated strains (HA-MRSA) have rarely spread or caused infections amongst healthy individuals in the community or amongst healthcare workers.
      • Otter J.A.
      • French G.L.
      Molecular epidemiology of community-associated meticillin-resistant Staphylococcus aureus in Europe.
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      However, MRSA infections in previously healthy individuals with no history of healthcare contact were noticed in the early 1990s in Australia and New Zealand, in the late 1990s in the USA, and in the early 2000s in Europe and elsewhere.
      • Otter J.A.
      • French G.L.
      Molecular epidemiology of community-associated meticillin-resistant Staphylococcus aureus in Europe.
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      Centers for Disease Control and Prevention
      Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus – Minnesota and North Dakota, 1997–1999.
      • Vandenesch F.
      • Naimi T.
      • Enright M.C.
      • et al.
      Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence.
      • Udo E.E.
      • Pearman J.W.
      • Grubb W.B.
      Genetic analysis of community isolates of methicillin-resistant Staphylococcus aureus in Western Australia.
      Subsequent molecular analysis showed that these infections were being caused by new types of MRSA which appeared to be common community strains of meticillin-susceptible S. aureus that had acquired the mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec) that encodes the meticillin resistance gene, mecA.
      • Enright M.C.
      • Robinson D.A.
      • Randle G.
      • Feil E.J.
      • Grundmann H.
      • Spratt B.G.
      The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA).
      • Deurenberg R.H.
      • Stobberingh E.E.
      The molecular evolution of hospital- and community-associated methicillin-resistant Staphylococcus aureus.
      There is considerable confusion in the literature regarding the definition and nomenclature of these new MRSA types.
      • Millar B.C.
      • Loughrey A.
      • Elborn J.S.
      • Moore J.E.
      Proposed definitions of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA).
      • Popovich K.J.
      • Weinstein R.A.
      Commentary: the graying of methicillin-resistant Staphylococcus aureus.
      For example, they have been termed ‘community-associated’, ‘community-acquired’, ‘community-onset’, ‘community’, ‘true’ and ‘de-novo’ types of MRSA.
      • Millar B.C.
      • Loughrey A.
      • Elborn J.S.
      • Moore J.E.
      Proposed definitions of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA).
      • Popovich K.J.
      • Weinstein R.A.
      Commentary: the graying of methicillin-resistant Staphylococcus aureus.
      • Witte W.
      • Braulke C.
      • Cuny C.
      • et al.
      Emergence of methicillin-resistant Staphylococcus aureus with Panton-Valentine leukocidin genes in central Europe.
      The most common term used to describe these strains was initially ‘community-acquired MRSA’,
      Centers for Disease Control and Prevention
      Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus – Minnesota and North Dakota, 1997–1999.
      • Vandenesch F.
      • Naimi T.
      • Enright M.C.
      • et al.
      Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence.
      but this has been widely replaced by ‘community-associated MRSA’ (CA-MRSA), reflecting uncertainty as to whether the MRSA was acquired in hospital or in the community.9,11–13 However, ‘CA-MRSA’ is poorly defined and used in different ways by different authors.
      • Millar B.C.
      • Loughrey A.
      • Elborn J.S.
      • Moore J.E.
      Proposed definitions of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA).
      This review will discuss the limitations of an epidemiological definition of CA-MRSA, and propose practical ways to define CA-MRSA by genotype.

      Definitions of CA-MRSA

      CA-MRSA were traditionally regarded as MRSA strains causing infection in previously healthy young patients without prior healthcare contact, susceptible to most non-β-lactam antimicrobial agents, and carrying Panton-Valentine leukocidin (PVL) genes and SCCmec types IV or V (Table I).
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      • Vandenesch F.
      • Naimi T.
      • Enright M.C.
      • et al.
      Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence.
      • Naimi T.S.
      • LeDell K.H.
      • Como-Sabetti K.
      • et al.
      Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection.
      However, as the microbiology and epidemiology of CA-MRSA have evolved, traditional definitions has broken down.
      • Millar B.C.
      • Loughrey A.
      • Elborn J.S.
      • Moore J.E.
      Proposed definitions of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA).
      Table IClinical, microbiological and genetic features of community-associated meticillin-resistant Staphylococcus aureus (MRSA)
      Clinical features
       Affected patients are less likely to have had healthcare contact
      • Naimi T.S.
      • LeDell K.H.
      • Como-Sabetti K.
      • et al.
      Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection.
      • Herold B.C.
      • Immergluck L.C.
      • Maranan M.C.
      • et al.
      Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk.
       Can affect healthy individuals of all ages
      • Naimi T.S.
      • LeDell K.H.
      • Como-Sabetti K.
      • et al.
      Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection.
      • Otter J.A.
      • French G.L.
      The emergence of community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital, 2000–2006.
       Characterized by primary SSTIs occurring in patients with no initial skin wound, especially abscesses
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
       Can cause life-threatening invasive infections such as bacteraemia and necrotizing pneumonia
      • Hidron A.I.
      • Low C.E.
      • Honig E.G.
      • Blumberg H.M.
      Emergence of community-acquired meticillin-resistant Staphylococcus aureus strain USA300 as a cause of necrotising community-onset pneumonia.
       Occasionally fatal in previously healthy paediatric patients and young adults
      • Hidron A.I.
      • Low C.E.
      • Honig E.G.
      • Blumberg H.M.
      Emergence of community-acquired meticillin-resistant Staphylococcus aureus strain USA300 as a cause of necrotising community-onset pneumonia.
       Apparent association with non-nasal sites of colonization
      • Yang E.S.
      • Tan J.
      • Eells S.
      • Rieg G.
      • Tagudar G.
      • Miller L.G.
      Body site colonization in patients with community-associated methicillin-resistant Staphylococcus aureus and other types of S. aureus skin infections.
       Recurrent SSTIs
      • Huang H.
      • Flynn N.M.
      • King J.H.
      • Monchaud C.
      • Morita M.
      • Cohen S.H.
      Comparisons of community-associated methicillin-resistant Staphylococcus aureus (MRSA) and hospital-associated MRSA infections in Sacramento, California.
      • Fritz S.A.
      • Epplin E.K.
      • Garbutt J.
      • Storch G.A.
      Skin infection in children colonized with community-associated methicillin-resistant Staphylococcus aureus.
       Transmission within family groups
      • Huijsdens X.W.
      • van Santen-Verheuvel M.G.
      • Spalburg E.
      • et al.
      Multiple cases of familial transmission of community-acquired methicillin-resistant Staphylococcus aureus.
      Microbiological features
       Faster growth rate and competitive advantage with HA-MRSA in vitro
      • Laurent F.
      • Lelievre H.
      • Cornu M.
      • et al.
      Fitness and competitive growth advantage of new gentamicin-susceptible MRSA clones spreading in French hospitals.
       Less frequent resistance to non-β-lactam antimicrobial classes
      • Vandenesch F.
      • Naimi T.
      • Enright M.C.
      • et al.
      Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence.
      • Naimi T.S.
      • LeDell K.H.
      • Como-Sabetti K.
      • et al.
      Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection.
       Low-level/heterogeneous expression of meticillin resistance
      • Laurent F.
      • Lelievre H.
      • Cornu M.
      • et al.
      Fitness and competitive growth advantage of new gentamicin-susceptible MRSA clones spreading in French hospitals.
      Genetic features
       Usually SCCmec IV or V
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      • Deurenberg R.H.
      • Stobberingh E.E.
      The molecular evolution of hospital- and community-associated methicillin-resistant Staphylococcus aureus.
       Epidemiological association with PVL carriage
      • Vandenesch F.
      • Naimi T.
      • Enright M.C.
      • et al.
      Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence.
      • Naimi T.S.
      • LeDell K.H.
      • Como-Sabetti K.
      • et al.
      Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection.
       Distinct and diverse MLST types and clonal complexes
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      • Deurenberg R.H.
      • Stobberingh E.E.
      The molecular evolution of hospital- and community-associated methicillin-resistant Staphylococcus aureus.
      SSTI, skin and soft tissue infection; HA-MRSA, healthcare-associated MRSA; SCCmec, staphylococcal cassette chromosome mec; PVL, Panton-Valentine leukocidin; MLST, multi-locus sequence type.

      Epidemiological definitions

      Epidemiological definitions of CA-MRSA are based on the timing of the first MRSA isolate relative to hospital admission, and were originally developed to determine whether an infection was likely to have been acquired during a hospital stay.
      • Coia J.E.
      • Duckworth G.J.
      • Edwards D.I.
      • et al.
      Guidelines for the control and prevention of meticillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities.
      Typically, these definitions regard MRSA colonization or infection presenting in community settings or at hospital re-admission as ‘community-acquired’ or ‘community-associated’, regardless of whether or not the patient has a history of healthcare contact.
      • Miller R.
      • Esmail H.
      • Peto T.
      • Walker S.
      • Crook D.
      • Wyllie D.
      Is MRSA admission bacteraemia community-acquired? A case control study.
      • Tacconelli E.
      • Venkataraman L.
      • De Girolami P.C.
      • D'Agata E.M.
      Methicillin-resistant Staphylococcus aureus bacteraemia diagnosed at hospital admission: distinguishing between community-acquired versus healthcare-associated strains.
      • Pearson A.
      Historical and changing epidemiology of healthcare-associated infections.
      MRSA causing such infections may then be misclassified as CA-MRSA. For example, several studies have found that most MRSA bacteraemias diagnosed at hospital admission, and therefore designated by some as community-acquired infections, are caused by nosocomial strains of MRSA (HA-MRSA) from a previous healthcare contact.
      • Miller R.
      • Esmail H.
      • Peto T.
      • Walker S.
      • Crook D.
      • Wyllie D.
      Is MRSA admission bacteraemia community-acquired? A case control study.
      • Tacconelli E.
      • Venkataraman L.
      • De Girolami P.C.
      • D'Agata E.M.
      Methicillin-resistant Staphylococcus aureus bacteraemia diagnosed at hospital admission: distinguishing between community-acquired versus healthcare-associated strains.
      Similarly, several reports in the era before the emergence of true or de-novo CA-MRSA described HA-MRSA strains causing infection in community settings as ‘community MRSA’.
      • Rosenberg J.
      Methicillin-resistant Staphylococcus aureus (MRSA) in the community: who's watching?.
      • Johnston B.L.
      Methicillin-resistant Staphylococcus aureus as a cause of community-acquired pneumonia – a critical review.
      The limitations of epidemiological definitions of CA-MRSA are illustrated by a study comparing two different epidemiological definitions of CA-MRSA: one identified 49% of 100 isolates as CA-MRSA, whereas the other only identified 5% as CA-MRSA.
      • Folden D.V.
      • Machayya J.A.
      • Sahmoun A.E.
      • et al.
      Estimating the proportion of community-associated methicillin-resistant Staphylococcus aureus: two definitions used in the USA yield dramatically different estimates.
      The US Centers for Disease Control and Prevention (CDC) proposed an epidemiological definition of CA-MRSA that has been widely adopted.
      • Folden D.V.
      • Machayya J.A.
      • Sahmoun A.E.
      • et al.
      Estimating the proportion of community-associated methicillin-resistant Staphylococcus aureus: two definitions used in the USA yield dramatically different estimates.
      • Rossney A.S.
      • Shore A.C.
      • Morgan P.M.
      • Fitzgibbon M.M.
      • O'Connell B.
      • Coleman D.C.
      The emergence and importation of diverse genotypes of MRSA harboring the Panton-Valentine leukocidin gene pvl reveals that pvl is a poor marker for community-acquired MRSA in Ireland.
      • Buck J.M.
      • Como-Sabetti K.
      • Harriman K.H.
      • et al.
      Community-associated methicillin-resistant Staphylococcus aureus, Minnesota, 2000–2003.
      • Huang H.
      • Flynn N.M.
      • King J.H.
      • Monchaud C.
      • Morita M.
      • Cohen S.H.
      Comparisons of community-associated methicillin-resistant Staphylococcus aureus (MRSA) and hospital-associated MRSA infections in Sacramento, California.
      In order to fulfil the current CDC definition of CA-MRSA, MRSA must be identified in the outpatient setting or less than 48 h after hospital admission in an individual with no medical history of MRSA infection or colonization, admission to a healthcare facility, dialysis, surgery or insertion of indwelling devices in the past year.
      • Millar B.C.
      • Loughrey A.
      • Elborn J.S.
      • Moore J.E.
      Proposed definitions of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA).
      • Buck J.M.
      • Como-Sabetti K.
      • Harriman K.H.
      • et al.
      Community-associated methicillin-resistant Staphylococcus aureus, Minnesota, 2000–2003.
      In the CDC definition, the inclusion of an assessment of previous healthcare contact means that MRSA linked to a hospitalization but presenting in the community or at hospital re-admission are classified correctly as HA-MRSA. Indeed, in a recent study from Oxford, none of the MRSA bacteraemias identified on hospital admission met the CDC definition of CA-MRSA.
      • Miller R.
      • Esmail H.
      • Peto T.
      • Walker S.
      • Crook D.
      • Wyllie D.
      Is MRSA admission bacteraemia community-acquired? A case control study.
      However, as more patients in the community are affected by CA-MRSA, repeat MRSA episodes are increasingly likely to be misclassified as HA-MRSA by epidemiological definitions.
      • Fritz S.A.
      • Epplin E.K.
      • Garbutt J.
      • Storch G.A.
      Skin infection in children colonized with community-associated methicillin-resistant Staphylococcus aureus.
      • Crum-Cianflone N.
      • Weekes J.
      • Bavaro M.
      Recurrent community-associated methicillin-resistant Staphylococcus aureus infections among HIV-infected persons: incidence and risk factors.
      A particular challenge to epidemiological definitions is the transmission of CA-MRSA among the injecting drug user/homeless group.
      • Cooke F.J.
      • Gkrania-Klotsas E.
      • Howard J.C.
      • et al.
      Clinical, molecular and epidemiological description of a cluster of community-associated methicillin-resistant Staphylococcus aureus isolates from injecting drug users with bacteraemia.
      • Otter J.A.
      • French G.L.
      Community-associated meticillin-resistant Staphylococcus aureus in injecting drug users and the homeless in south London.
      These patients often have a history of previous hospital admission for other reasons, but their infections may be caused by CA-MRSA strains originally acquired in the community.
      Epidemiological definitions are further limited by the emergence of CA-MRSA clones as an increasingly common cause of healthcare-associated infection.
      • Popovich K.J.
      • Weinstein R.A.
      Commentary: the graying of methicillin-resistant Staphylococcus aureus.
      • Otter J.A.
      • French G.L.
      Nosocomial transmission of community-associated methicillin-resistant Staphylococcus aureus: an emerging threat.
      • Popovich K.J.
      • Weinstein R.A.
      • Hota B.
      Are community-associated methicillin-resistant Staphylococcus aureus (MRSA) strains replacing traditional nosocomial MRSA strains?.
      • Otter J.A.
      • French G.L.
      Community-associated meticillin-resistant Staphylococcus aureus strains as a cause of healthcare-associated infection.
      Purely epidemiological definitions of CA-MRSA do not consider the genetic background of the MRSA involved and will misclassify CA-MRSA acquired in hospital.

      Need for a genotypic definition

      Millar et al. proposed guidelines for developing a definition of CA-MRSA combining epidemiological factors, antimicrobial susceptibility (AMS) pattern, clinical presentation and SCCmec type.
      • Millar B.C.
      • Loughrey A.
      • Elborn J.S.
      • Moore J.E.
      Proposed definitions of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA).
      However, although this is an improvement on the CDC definition, these guidelines are confounded by CA-MRSA acquired in healthcare settings which only meet some of the proposed criteria for CA-MRSA.
      • Millar B.C.
      • Loughrey A.
      • Elborn J.S.
      • Moore J.E.
      Proposed definitions of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA).
      Also, the guidelines recommend the use of SCCmec typing alone for inferring the MRSA genetic background, but this is not useful for determining the MRSA lineage because isolates with a non-typeable SCCmec cassette may be missed, and SCCmec IV carrying HA-MRSA lineages such as ST22-IV (EMRSA-15) and ST5-IV (USA800/paediatric clone) may be misclassified as CA-MRSA.
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      • Otter J.A.
      • Klein J.L.
      • Watts T.L.
      • Kearns A.M.
      • French G.L.
      Identification and control of an outbreak of ciprofloxacin-susceptible EMRSA-15 on a neonatal unit.
      CA-MRSA are usually common community types of meticillin-susceptible S. aureus that have acquired mecA de novo.
      • Enright M.C.
      • Robinson D.A.
      • Randle G.
      • Feil E.J.
      • Grundmann H.
      • Spratt B.G.
      The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA).
      • Deurenberg R.H.
      • Stobberingh E.E.
      The molecular evolution of hospital- and community-associated methicillin-resistant Staphylococcus aureus.
      Therefore, it is proposed that combining a genotyping method [such as multi-locus sequence typing (MLST), spa or pulsed-field gel electrophoresis] with SCCmec analysis to infer the likely origin of the MRSA is the best way to define CA-MRSA strains at the current time. These isolates may be PVL-positive or PVL-negative, have any clinical presentation, have any AMS pattern, and can be classified as either healthcare- or community-associated using epidemiological criteria.

      Practical definition of CA-MRSA

      The introduction of a genotypic method into the definition of CA-MRSA adds extra cost, time and requirement for laboratory equipment, expertise and experience to define these strains. However, the costs of genotyping are decreasing, and the equipment and expertise required, particularly for spa typing, is within the capabilities of most clinical laboratories.
      • Aires-de-Sousa M.
      • Boye K.
      • de Lencastre H.
      • et al.
      High interlaboratory reproducibility of DNA sequence-based typing of bacteria in a multicenter study.
      Furthermore, collaboration with reference centres can be sought to provide genotyping. If this approach becomes more widely accepted and the demands for genotyping increase, it is likely that simpler/automated methods may become commercially available.
      Despite these difficulties, the authors believe that future studies of MRSA should use genotypic rather than epidemiological definitions of CA-MRSA. Ideally, all isolates should be genotyped, but in many circumstances, molecular markers or AMS profiles can be used to select representative strains for more detailed genotypic analysis, as discussed below.

      Molecular markers

      There is no single, stable genetic marker for CA-MRSA strains. PVL has been proposed as a marker of CA-MRSA.
      • Millar B.C.
      • Loughrey A.
      • Elborn J.S.
      • Moore J.E.
      Proposed definitions of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA).
      • Rossney A.S.
      • Shore A.C.
      • Morgan P.M.
      • Fitzgibbon M.M.
      • O'Connell B.
      • Coleman D.C.
      The emergence and importation of diverse genotypes of MRSA harboring the Panton-Valentine leukocidin gene pvl reveals that pvl is a poor marker for community-acquired MRSA in Ireland.
      • Ellington M.J.
      • Perry C.
      • Ganner M.
      • et al.
      Clinical and molecular epidemiology of ciprofloxacin-susceptible MRSA encoding PVL in England and Wales.
      There is undoubtedly an epidemiological association between CA-MRSA and the carriage of PVL,
      • Vandenesch F.
      • Naimi T.
      • Enright M.C.
      • et al.
      Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence.
      • Naimi T.S.
      • LeDell K.H.
      • Como-Sabetti K.
      • et al.
      Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection.
      but some globally disseminated CA-MRSA clones do not carry PVL.
      • Rossney A.S.
      • Shore A.C.
      • Morgan P.M.
      • Fitzgibbon M.M.
      • O'Connell B.
      • Coleman D.C.
      The emergence and importation of diverse genotypes of MRSA harboring the Panton-Valentine leukocidin gene pvl reveals that pvl is a poor marker for community-acquired MRSA in Ireland.
      • Zhang K.
      • McClure J.A.
      • Elsayed S.
      • Tan J.
      • Conly J.M.
      Coexistence of Panton-Valentine leukocidin-positive and -negative community-associated methicillin-resistant Staphylococcus aureus USA400 sibling strains in a large Canadian health-care region.
      • Nimmo G.R.
      • Coombs G.W.
      Community-associated methicillin-resistant Staphylococcus aureus (MRSA) in Australia.
      Many of the reports of CA-MRSA have come from the USA, where USA300 (ST8-IV), which is predominantly PVL-positive,
      • Larsen A.R.
      • Goering R.
      • Stegger M.
      • et al.
      Two distinct clones of methicillin-resistant Staphylococcus aureus (MRSA) with the same USA300 pulsed-field gel electrophoresis profile: a potential pitfall for identification of USA300 community-associated MRSA.
      is the dominant clone.
      • Otter J.A.
      • French G.L.
      Molecular epidemiology of community-associated meticillin-resistant Staphylococcus aureus in Europe.
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      • Popovich K.J.
      • Weinstein R.A.
      • Hota B.
      Are community-associated methicillin-resistant Staphylococcus aureus (MRSA) strains replacing traditional nosocomial MRSA strains?.
      • Otter J.A.
      • Havill N.L.
      • Boyce J.M.
      • French G.L.
      Comparison of community-associated methicillin-resistant Staphylococcus aureus from teaching hospitals in London and the USA, 2004–2006: where is USA300 in the UK?.
      In contrast to the dominance of USA300 in the USA, the common CA-MRSA clones in Europe and elsewhere are heterogeneous, including a mixture of PVL-positive and PVL-negative clones.
      • Otter J.A.
      • French G.L.
      Molecular epidemiology of community-associated meticillin-resistant Staphylococcus aureus in Europe.
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      Successful PVL-negative CA-MRSA clones include ST1-IV (WA-MRSA-1), which is the most common CA-MRSA clone in Western Australia
      • Nimmo G.R.
      • Coombs G.W.
      Community-associated methicillin-resistant Staphylococcus aureus (MRSA) in Australia.
      and was the most common CA-MRSA clone at a London hospital from 2000 to 2006,
      • Otter J.A.
      • French G.L.
      The emergence of community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital, 2000–2006.
      and the ST398-V pig-associated clone in Europe.
      • Huijsdens X.W.
      • van Dijke B.J.
      • Spalburg E.
      • et al.
      Community-acquired MRSA and pig-farming.
      One study reported the co-existence of sibling clones of PVL-positive and PVL-negative USA400 in Canada.
      • Zhang K.
      • McClure J.A.
      • Elsayed S.
      • Tan J.
      • Conly J.M.
      Coexistence of Panton-Valentine leukocidin-positive and -negative community-associated methicillin-resistant Staphylococcus aureus USA400 sibling strains in a large Canadian health-care region.
      A study from Ireland found that only two (7%) of 30 isolates that met the CDC definition of CA-MRSA carried PVL. Therefore, although MRSA producing PVL are likely to be CA-MRSA, PVL production should not be used as part of the definition of CA-MRSA.
      CA-MRSA usually carry SCCmec types IV or V, whereas HA-MRSA usually carry SCCmec types I–III.
      • Deurenberg R.H.
      • Stobberingh E.E.
      The molecular evolution of hospital- and community-associated methicillin-resistant Staphylococcus aureus.
      International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements (IWG-SCC)
      Classification of staphylococcal cassette chromosome mec (SCCmec): guidelines for reporting novel SCCmec elements.
      Some researchers have used the carriage of SCCmec IV as a molecular marker for CA-MRSA.
      • Maree C.L.
      • Daum R.S.
      • Boyle-Vavra S.
      • Matayoshi K.
      • Miller L.G.
      Community-associated methicillin-resistant Staphylococcus aureus isolates causing healthcare-associated infections.
      • Davis S.L.
      • Rybak M.J.
      • Amjad M.
      • Kaatz G.W.
      • McKinnon P.S.
      Characteristics of patients with healthcare-associated infection due to SCCmec type IV methicillin-resistant Staphylococcus aureus.
      For example, a retrospective study from Chicago used an AMS-based algorithm for the presumptive detection of ‘SCCmec IV phenotype’ isolates, which were used to infer changes in the prevalence of CA-MRSA.
      • Maree C.L.
      • Daum R.S.
      • Boyle-Vavra S.
      • Matayoshi K.
      • Miller L.G.
      Community-associated methicillin-resistant Staphylococcus aureus isolates causing healthcare-associated infections.
      Since the study was performed in the USA, this approach was valid given the dominance of SCCmec IV USA300 and the fact that SCCmec IV HA-MRSA lineages are rare in the USA.
      However, the SCCmec region is variable, and new types and subtypes are emerging constantly, leading to problems with nomenclature.
      • Deurenberg R.H.
      • Stobberingh E.E.
      The molecular evolution of hospital- and community-associated methicillin-resistant Staphylococcus aureus.
      International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements (IWG-SCC)
      Classification of staphylococcal cassette chromosome mec (SCCmec): guidelines for reporting novel SCCmec elements.
      For example, SCCmec V, which is carried by successful CA-MRSA lineages,
      • Otter J.A.
      • French G.L.
      Molecular epidemiology of community-associated meticillin-resistant Staphylococcus aureus in Europe.
      was first reported in 2004, a decade after the first emergence of CA-MRSA.
      • Ito T.
      • Ma X.X.
      • Takeuchi F.
      • Okuma K.
      • Yuzawa H.
      • Hiramatsu K.
      Novel type V staphylococcal cassette chromosome mec driven by a novel cassette chromosome recombinase, ccrC.
      A particular problem with the use of SCCmec type as a marker for CA-MRSA is the presence of successful hospital lineages carrying SCCmec IV in some parts of the world. For example, unlike most other parts of the world, the most common HA-MRSA clone in the UK, ST22 EMRSA-15, is SCCmec IV,
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      • Otter J.A.
      • Klein J.L.
      • Watts T.L.
      • Kearns A.M.
      • French G.L.
      Identification and control of an outbreak of ciprofloxacin-susceptible EMRSA-15 on a neonatal unit.
      as is the ST5/USA800 paediatric clone which is disseminated in the USA and South America.
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      Furthermore, these SCCmec IV carrying HA-MRSA tend to be relatively susceptible to antimicrobial agents, compounding the likelihood that they will be misclassified as CA-MRSA unless their lineage is determined.
      • Otter J.A.
      • Klein J.L.
      • Watts T.L.
      • Kearns A.M.
      • French G.L.
      Identification and control of an outbreak of ciprofloxacin-susceptible EMRSA-15 on a neonatal unit.

      AMS-based markers

      The SCCmec I–III cassettes, common in HA-MRSA, carry additional antimicrobial resistance genes that are not present in the smaller SCCmec IV and V cassettes associated with CA-MRSA.
      • Millar B.C.
      • Loughrey A.
      • Elborn J.S.
      • Moore J.E.
      Proposed definitions of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA).
      • Larsen A.R.
      • Goering R.
      • Stegger M.
      • et al.
      Two distinct clones of methicillin-resistant Staphylococcus aureus (MRSA) with the same USA300 pulsed-field gel electrophoresis profile: a potential pitfall for identification of USA300 community-associated MRSA.
      Furthermore, CA-MRSA have emerged without the antimicrobial pressure that selects for multiple antimicrobial resistance in hospitals.
      • Lowy F.D.
      Antimicrobial resistance: the example of Staphylococcus aureus.
      Consequently, the first CA-MRSA were susceptible to non-β-lactam antimicrobial agents,
      • Vandenesch F.
      • Naimi T.
      • Enright M.C.
      • et al.
      Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence.
      • Naimi T.S.
      • LeDell K.H.
      • Como-Sabetti K.
      • et al.
      Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection.
      and this susceptibility has been used as a screening marker for these strains. For example, ciprofloxacin susceptibility has been used as a phenotypic marker of CA-MRSA in the UK.
      • Aires-de-Sousa M.
      • Boye K.
      • de Lencastre H.
      • et al.
      High interlaboratory reproducibility of DNA sequence-based typing of bacteria in a multicenter study.
      • Davis S.L.
      • Rybak M.J.
      • Amjad M.
      • Kaatz G.W.
      • McKinnon P.S.
      Characteristics of patients with healthcare-associated infection due to SCCmec type IV methicillin-resistant Staphylococcus aureus.
      • Ito T.
      • Ma X.X.
      • Takeuchi F.
      • Okuma K.
      • Yuzawa H.
      • Hiramatsu K.
      Novel type V staphylococcal cassette chromosome mec driven by a novel cassette chromosome recombinase, ccrC.
      Several studies have attempted to assess the accuracy of AMS-based algorithms for the presumptive identification of CA-MRSA.
      • Otter J.A.
      • French G.L.
      Utility of antimicrobial susceptibility-based algorithms for the presumptive identification of genotypically-defined community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital.
      • Popovich K.
      • Hota B.
      • Rice T.
      • Aroutcheva A.
      • Weinstein R.A.
      Phenotypic prediction rule for community-associated methicillin-resistant Staphylococcus aureus.
      • Gbaguidi-Haore H.
      • Thouverez M.
      • Couetdic G.
      • Cholley P.
      • Talon D.
      • Bertrand X.
      Usefulness of antimicrobial resistance pattern for detecting PVL- or TSST-1-producing MRSA in a French university hospital.
      However, even the best AMS-based classification systems only have a sensitivity of 70–80%.
      • Otter J.A.
      • French G.L.
      Utility of antimicrobial susceptibility-based algorithms for the presumptive identification of genotypically-defined community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital.
      • Popovich K.
      • Hota B.
      • Rice T.
      • Aroutcheva A.
      • Weinstein R.A.
      Phenotypic prediction rule for community-associated methicillin-resistant Staphylococcus aureus.
      • Gbaguidi-Haore H.
      • Thouverez M.
      • Couetdic G.
      • Cholley P.
      • Talon D.
      • Bertrand X.
      Usefulness of antimicrobial resistance pattern for detecting PVL- or TSST-1-producing MRSA in a French university hospital.
      For example, in one UK study, the use of ciprofloxacin susceptibility as a marker missed approximately one-third of CA-MRSA isolates,
      • Otter J.A.
      • French G.L.
      Utility of antimicrobial susceptibility-based algorithms for the presumptive identification of genotypically-defined community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital.
      and it is likely that mutational ciprofloxacin resistance will increase in these strains in future.
      • Lowy F.D.
      Antimicrobial resistance: the example of Staphylococcus aureus.
      AMS profiles tend to vary with lineage, thus algorithms for the presumptive identification of CA-MRSA will need to be developed locally.
      • Vandenesch F.
      • Naimi T.
      • Enright M.C.
      • et al.
      Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence.
      • Otter J.A.
      • Havill N.L.
      • Boyce J.M.
      • French G.L.
      Comparison of community-associated methicillin-resistant Staphylococcus aureus from teaching hospitals in London and the USA, 2004–2006: where is USA300 in the UK?.
      • Otter J.A.
      • French G.L.
      Utility of antimicrobial susceptibility-based algorithms for the presumptive identification of genotypically-defined community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital.
      The resolution of AMS-based algorithms is likely to decrease further over time as CA-MRSA develop broader antimicrobial resistance by continued exposure to antimicrobial selective pressure in hospitals.
      • Huang H.
      • Flynn N.M.
      • King J.H.
      • Monchaud C.
      • Morita M.
      • Cohen S.H.
      Comparisons of community-associated methicillin-resistant Staphylococcus aureus (MRSA) and hospital-associated MRSA infections in Sacramento, California.
      • Diep B.A.
      • Chambers H.F.
      • Graber C.J.
      • et al.
      Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone USA300 in men who have sex with men.
      • Ellington M.J.
      • Ganner M.
      • Warner M.
      • Cookson B.D.
      • Kearns A.M.
      Polyclonal multiply antibiotic-resistant methicillin-resistant Staphylococcus aureus with Panton-Valentine leucocidin in England.
      In addition, a particular problem with using antimicrobial susceptibility as a phenotypic marker of CA-MRSA in the UK is that the most common cause of HA-MRSA, EMRSA-15, is typically susceptible to most non-β-lactam antimicrobials.
      • Otter J.A.
      • Klein J.L.
      • Watts T.L.
      • Kearns A.M.
      • French G.L.
      Identification and control of an outbreak of ciprofloxacin-susceptible EMRSA-15 on a neonatal unit.
      Furthermore, useful algorithms will need to be assessed periodically to reflect changes in resistance patterns.

      Addressing variation in the molecular epidemiology of CA-MRSA

      Genotypic definitions of CA-MRSA will need to reflect differences in the molecular epidemiology of community and healthcare-associated MRSA, and variations in the molecular techniques adopted between countries and laboratories.
      • Otter J.A.
      • French G.L.
      Molecular epidemiology of community-associated meticillin-resistant Staphylococcus aureus in Europe.
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      A genotypic definition is easier to derive in the USA and Latin America, where predominant HA-MRSA lineages are not SCCmec IV and USA300 is so prominent among CA-MRSA.
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      • Otter J.A.
      • Havill N.L.
      • Boyce J.M.
      • French G.L.
      Comparison of community-associated methicillin-resistant Staphylococcus aureus from teaching hospitals in London and the USA, 2004–2006: where is USA300 in the UK?.
      • Reyes J.
      • Rincon S.
      • Diaz L.
      • et al.
      Dissemination of methicillin-resistant Staphylococcus aureus USA300 sequence type 8 lineage in Latin America.
      Similarly, genotypic definitions are straightforward where there is a predominant CA-MRSA clone; for example, PVL-positive ST30-IV (‘SWP’) in Uruguay,
      • Benoit S.R.
      • Estivariz C.
      • Mogdasy C.
      • et al.
      Community strains of methicillin-resistant Staphylococcus aureus as potential cause of healthcare-associated infections, Uruguay, 2002–2004.
      a novel PVL-positive ST5-IV clone in Argentina,
      • Sola C.
      • Saka H.A.
      • Vindel A.
      • Bocco J.L.
      Emergence and dissemination of a community-associated methicillin-resistant Panton-Valentine leucocidin-positive Staphylococcus aureus clone sharing the sequence type 5 lineage with the most prevalent nosocomial clone in the same region of Argentina.
      PVL-positive ST22-IV and ST772-V in India,
      • D'Souza N.
      • Rodrigues C.
      • Mehta A.
      Molecular characterization of methicillin-resistant Staphylococcus aureus with emergence of epidemic clones of sequence type (ST) 22 and ST 772 in Mumbai, India.
      PVL-positive ST80-IV in North Africa,
      • Antri K.
      • Rouzic N.
      • Dauwalder O.
      • et al.
      High prevalence of methicillin-resistant Staphylococcus aureus clone ST80-IV in hospital and community settings in Algiers.
      • Ramdani-Bouguessa N.
      • Bes M.
      • Meugnier H.
      • et al.
      Detection of methicillin-resistant Staphylococcus aureus strains resistant to multiple antibiotics and carrying the Panton-Valentine leukocidin genes in an Algiers hospital.
      and PVL-positive ST59-VII in Taiwan.
      • Boyle-Vavra S.
      • Ereshefsky B.
      • Wang C.C.
      • Daum R.S.
      Successful multiresistant community-associated methicillin-resistant Staphylococcus aureus lineage from Taipei, Taiwan, that carries either the novel staphylococcal chromosome cassette mec (SCCmec) type VT or SCCmec type IV.
      • Takano T.
      • Higuchi W.
      • Otsuka T.
      • et al.
      Novel characteristics of community-acquired methicillin-resistant Staphylococcus aureus strains belonging to multilocus sequence type 59 in Taiwan.
      • Chen C.J.
      • Hsueh P.R.
      • Su L.H.
      • Chiu C.H.
      • Lin T.Y.
      • Huang Y.C.
      Change in the molecular epidemiology of methicillin-resistant Staphylococcus aureus bloodstream infections in Taiwan.
      However, developing a genotypic definition is more difficult in Europe and Australia where CA-MRSA are currently characterized by genotypic heterogeneity.
      • Otter J.A.
      • French G.L.
      Molecular epidemiology of community-associated meticillin-resistant Staphylococcus aureus in Europe.
      • Vandenesch F.
      • Naimi T.
      • Enright M.C.
      • et al.
      Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence.
      • Nimmo G.R.
      • Coombs G.W.
      Community-associated methicillin-resistant Staphylococcus aureus (MRSA) in Australia.
      • Tong S.Y.
      • Lilliebridge R.A.
      • Bishop E.J.
      • et al.
      Clinical correlates of Panton-Valentine leukocidin (PVL), PVL isoforms, and clonal complex in the Staphylococcus aureus population of Northern Australia.
      The global molecular epidemiology of CA-MRSA is poorly described, so it is difficult to judge how easy it would be to derive a workable genotypic definition in many parts of the world.
      • Otter J.A.
      • French G.L.
      Molecular epidemiology of community-associated meticillin-resistant Staphylococcus aureus in Europe.
      • Chambers H.F.
      • Deleo F.R.
      Waves of resistance: Staphylococcus aureus in the antibiotic era.
      The present authors recently developed a genotypic definition of CA-MRSA at their London teaching hospital,
      • Otter J.A.
      • French G.L.
      Utility of antimicrobial susceptibility-based algorithms for the presumptive identification of genotypically-defined community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital.
      which currently has a low but apparently increasing prevalence of CA-MRSA,
      • Otter J.A.
      • French G.L.
      The emergence of community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital, 2000–2006.
      and the predominant HA-MRSA clone is ST22-IV EMRSA-15.
      • Ellington M.J.
      • Hope R.
      • Livermore D.M.
      • et al.
      Decline of EMRSA-16 amongst methicillin-resistant Staphylococcus aureus causing bacteraemias in the UK between 2001 and 2007.
      CA-MRSA were defined as isolates that were SCCmec IV or V that did not have a spa type in the same clonal cluster as EMRSA-15 (using Based Upon Repeat Pattern clustering).
      • Otter J.A.
      • French G.L.
      The emergence of community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital, 2000–2006.
      Isolates with non-typeable SCCmec regions were defined as CA-MRSA because they were considered to be unlikely to represent epidemic hospital lineages, and all other isolates were classified as HA-MRSA.
      • Otter J.A.
      • French G.L.
      Utility of antimicrobial susceptibility-based algorithms for the presumptive identification of genotypically-defined community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital.
      In common with previous reports (Table I), isolates defined as CA-MRSA were more likely to be associated with younger patients, abscess formation and PVL production; classified as community acquired by epidemiological criteria; and resistant to fewer classes of antimicrobial agents than isolates defined as HA-MRSA.
      • Otter J.A.
      • French G.L.
      Utility of antimicrobial susceptibility-based algorithms for the presumptive identification of genotypically-defined community-associated methicillin-resistant Staphylococcus aureus at a London teaching hospital.
      Until the emergence of CA-MRSA as a cause of healthcare-associated infection, both genotypic and epidemiological definitions would have identified a broadly similar set of isolates. This is now not the case, as illustrated by the fact that 70% of these CA-MRSA isolates were classified as HA-MRSA by epidemiological criteria. This highlights the limitations of epidemiological classifications if used for presumptive identification of CA-MRSA types, and thus supports the use of a genotypic definition. Although the authors suspect that many of these patients, such as intravenous drug users, probably had community acquisition followed by repeated hospital contacts, genuine nosocomial transmission of CA-MRSA strains appears to be occurring with increasing frequency in other parts of the world.
      • Popovich K.J.
      • Weinstein R.A.
      Commentary: the graying of methicillin-resistant Staphylococcus aureus.
      • Otter J.A.
      • French G.L.
      Nosocomial transmission of community-associated methicillin-resistant Staphylococcus aureus: an emerging threat.
      • Popovich K.J.
      • Weinstein R.A.
      • Hota B.
      Are community-associated methicillin-resistant Staphylococcus aureus (MRSA) strains replacing traditional nosocomial MRSA strains?.
      • Otter J.A.
      • French G.L.
      Community-associated meticillin-resistant Staphylococcus aureus strains as a cause of healthcare-associated infection.

      Acquisition and onset of clinical infection

      Although it is essential to have clear definitions to distinguish between HA- and CA-MRSA strain types, the time and place of onset of colonization and/or infection are also important for epidemiological analysis, and infection prevention and control. Thus, CA-MRSA can be acquired in either community (common) or healthcare (uncommon but increasing) settings. HA-MRSA strains are nearly always acquired during healthcare contact, but with both strain types, the onset of infection may be in either the community or in hospital. Where the information is available, MRSA infections should therefore be characterized as: (1) caused by HA- or CA-MRSA strain type; (2) acquired in community or healthcare settings; and (3) onset in the community or healthcare facility. These data are important for epidemiological analysis, risk assessment, regulatory reporting, and the development of appropriate infection prevention and control in the community, healthcare facility and community/hospital interface.

      Recommendations and conclusion

      At the current time, MRSA strains involved in outbreaks should either be typed by individual hospital laboratories or referred to reference laboratories in order to determine whether they are CA-MRSA or HA-MRSA strain types, because a wider group of patients and staff may be at risk and novel control strategies may be required for CA-MRSA.
      • Otter J.A.
      • French G.L.
      Nosocomial transmission of community-associated methicillin-resistant Staphylococcus aureus: an emerging threat.
      • Otter J.A.
      • French G.L.
      Community-associated meticillin-resistant Staphylococcus aureus strains as a cause of healthcare-associated infection.
      • Teare L.
      • Shelley O.P.
      • Millership S.
      • Kearns A.
      Outbreak of Panton-Valentine leucocidin-positive meticillin-resistant Staphylococcus aureus in a regional burns unit.
      Novel strategies may include hospital staff screening, increased follow-up of cases with hospital and community onset to reduce household transmission, enhanced infection prevention and control measures in community settings, and a focus on preventing transmission of MRSA from livestock to humans in affected areas.
      • Otter J.A.
      • French G.L.
      Molecular epidemiology of community-associated meticillin-resistant Staphylococcus aureus in Europe.
      • Otter J.A.
      • French G.L.
      Community-associated meticillin-resistant Staphylococcus aureus strains as a cause of healthcare-associated infection.
      • Kock R.
      • Becker K.
      • Cookson B.
      • et al.
      Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe.
      Periodic investigation of AMS patterns among MRSA infections, perhaps combined with typing of local sets of isolates, would also be useful to ensure that empiric therapy is appropriate, given that the emergence of CA-MRSA in some parts of the world has forced a change of empiric therapy of staphylococcal skin infections to cover MRSA.
      • Moran G.J.
      • Amii R.N.
      • Abrahamian F.M.
      • Talan D.A.
      Methicillin-resistant Staphylococcus aureus in community-acquired skin infections.
      • Chuck E.A.
      • Frazee B.W.
      • Lambert L.
      • McCabe R.
      The benefit of empiric treatment for methicillin-resistant Staphylococcus aureus.
      Reference laboratories should continue to type representative sets of isolates periodically to ensure that MRSA trends and emerging strain types are monitored adequately.
      • Ellington M.J.
      • Perry C.
      • Ganner M.
      • et al.
      Clinical and molecular epidemiology of ciprofloxacin-susceptible MRSA encoding PVL in England and Wales.
      • Ellington M.J.
      • Hope R.
      • Livermore D.M.
      • et al.
      Decline of EMRSA-16 amongst methicillin-resistant Staphylococcus aureus causing bacteraemias in the UK between 2001 and 2007.
      For full assessment of their epidemiology, MRSA infections should be characterized as: (1) caused by HA- or CA-MRSA strain types; (2) acquired in community or healthcare settings; and (3) onset in the community or healthcare facility.

      Conflict of interest statements

      JAO is employed part-time by Bioquell UK Ltd. GLF declares no potential conflict of interest.

      Funding sources

      None.

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