Epidemic Methicillin-resistant Staphylococcus Aureus Strains Research Articles

Complete Genome Sequences of Canadian Epidemic Methicillin-Resistant Staphylococcus aureus Strains CMRSA3 and CMRSA6.

Methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 8 (CC8) sequence type 239 (ST239) represents a predominant hospital-associated MRSA sublineage present worldwide. The Canadian epidemic MRSA strains CMRSA3 and CMRSA6 are moderately virulent members of this group but are closely related to the highly virulent strain TW20. Whole-genome sequencing of CMRSA3 and CMRSA6 was conducted to identify genetic determinants associated with their virulence.

Distribution of sasX, pvl, and qacA/B genes in epidemic methicillin-resistant Staphylococcus aureus strains isolated from East China.

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen. Various virulence and antiseptic-resistant factors increase the pathogenicity of MRSA strains and allow for increased infection rates.PurposeThe purpose of this study was to investigate the prevalence and distribution of virulence-associated and antiseptic-resistant genes from epidemic MRSA strains isolated from East China.MethodsA newly designed multiplex PCR assay was used to assess whether the virulence-associated genes sasX and pvl and the chlorhexidine tolerance gene qacA/B were present in 189 clinical isolates of MRSA. Multilocus sequence typing (MLST) and Staphylococcal protein A (spa) typing of these isolates were also performed. The frequency of these genes in isolates with epidemic sequence types (STs) was investigated.ResultsTwenty STs and 36 spa types with five epidemic clones (ST5-t311, ST59-t437, ST5-t002, ST239-t030, and ST239-t037) were identified. The prevalence of sasX, pvl, and qacA/B in all isolates was 5.8%, 10.1%, and 20.1%, respectively. The prevalences of these genes in isolates with ST5, ST59, ST239, and other ST genetic backgrounds were all significantly different (P<0.001). Isolates that had the highest frequency of sasX, pvl, or qacA/B were ST239 (33.3%), ST59 (28.9%), and ST5 (34.1%), respectively. The gene distribution pattern from all of the isolates showed that sasX−pvl−qacA/B+, sasX−pvl+qacA/B−, and sasX+pvl−qacA/B− were closely associated with epidemic clones ST5-t311, ST59-t437, and ST239-t037, respectively.ConclusionThere are significant differences in the prevalence of virulence-associated and antiseptic-resistant genes in epidemic MRSA strains. Using this information, more effective control and prevention strategies for nosocomial MRSA infections can be developed.

Characterization of methicillin-resistant Staphylococcus aureus isolated at Tripoli Medical Center, Libya, between 2008 and 2014.

Bacterial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) represent a well-known public health problem affecting both healthcare-associated and community populations. Past studies have clearly shown the value of characterizing problem organisms including MRSA through the use of molecular techniques (i.e. strain typing), with the aim of informing local, regional and national efforts in epidemiological analysis and infection control. The country of Libya represents a challenge for such analysis due to limited historical infectious disease information and major political unrest culminating in the Libyan Civil War (Libyan Revolution) in 2011. A MRSA study population of 202 isolates, cultured from patients in Tripoli Medical Center through this historical period (2008-2014), was characterized by both phenotypic and molecular methods. The results revealed a diversification of epidemic MRSA strains over time with generally increasing resistance to fluoroquinolone antibiotics. The study identified prevalent MRSA in comparison to known global epidemic types, providing unique insight into the change of strains and/or characteristics over time especially with reference to the potential influence of the political revolution (i.e. pre- and post-2011).

MRSAspat1081, a Highly Transmissible Strain Endemic to Hong Kong, China, in the Netherlands

MRSA<i>spa</i>t1081, a Highly Transmissible Strain Endemic to Hong Kong, China, in the Netherlands

Methicillin-ResistantStaphylococcus aureus

Despite the availability of effective preventative and therapeutic strategies, methicillin-resistant Staphylococcus aureus (MRSA) remains amajor cause of health care–associated and, more recently, community-acquired infections. Since the introduction of methicillin in 1959, epidemics due to different clones ofMRSAhave occurred in diverse geographic regions.1 The result has been the persistence of MRSA as an important pathogen worldwide. In the United States, themost recentMRSA epidemic has been due to the clone USA300. USA300 has been responsible for themajorityof communityandhealth care–associatedoutbreaks since the early 1990s.1 Until recently, thenumber of infections has continued to rise, especially in urban centers. While themajority of these have been skin and soft-tissue infections (SSTIs), a notable minority have been invasive and life-threatening.1 Two articles in this issueof JAMAInternalMedicineprovide additional insight into both the incidence and the risks associatedwithdevelopmentofMRSA infections.Danteset al2provide evidence that the overall incidence of invasiveMRSA infections nationally is declining. Casey et al3 perform an ecological investigation; they find that individuals livingnear high-density farming operations (ie, farms having an animal density of 2 animals or 1000-lbs live weight per acre) or near crop fieldsusingmanure exported from thehigh-density livestock farms are at increased risk of developingMRSA or other bacterial SSTIs. Both studies raise questions thatwarrant further investigation. Dantes et al2 useddata from theActiveBacterial Core Surveillance Program (ABCSP) to compare the national incidence rate of invasive MRSA infections for the years 2005 through 2011. The findings are of special importance because of the surveymethods that areusedand the size of the sample population (approximately 15 million). The ABCSP is an active surveillance program that is population based and includes a reviewofmedical records. It serves as amodel for this type of surveillance. The results show that the incidence of health care–associated community-onset and hospital-onset invasive MRSA infections have declined by 27.7% and 54.2%, respectively. The findings are consistent with several earlier reports including one from the same group. This impressive declinemaywellbeduetothe implementationof infectioncontrol efforts at thehospital level; however, it is alsopossible that the epidemic MRSA strains circulating in the health care setting have evolved, becoming less virulent. In contrast to the decline inhealth care–associatedMRSA, the estimated reduction in incidence of community-associated infections was a modest 5%. In addition to the evidence that the incidenceofMRSA infections is declining, the study highlights 2 important points. The first is the observation that there is an increased risk of recurrent infection among recentlyhospitalizedpatientswith healthcare–associatedcommunity-onset infections.Thesepatients had a 64% risk of infection at 3 months or less followingdischarge.Others have also reported ahigh risk of reinfection in discharged patients either infected or colonized with MRSA.4 Possible explanations for the patients’ increased risk include underlyingmedical comorbidities, persistent colonizationor recolonizationwithMRSA,orexposure tosimilar risks of MRSA infection following discharge. This subset of patients would appear to be candidates for studies directed at reducing their high risk of recurrent infection. The second finding is the limited change in the incidence of communityassociated infections. This is in marked contrast with the reduction in the incidence of health care–associated infections. As noted by the authors, the study highlights the need for a greater understanding of how these epidemic MRSA strains spread and initiate infection within the community. Related articles pages 1970 and 1980 Research Original Investigation National Burden of Invasive MRSA Infections

Rapid Microarray-Based Identification of Different mecA Alleles in Staphylococci

To screen isolates and to identify mecA alleles, published mecA sequences were analyzed, and a microarray for the rapid discrimination of mecA alleles was designed. A GenBank analysis yielded 135 full-length gene sequences annotated as mecA. These sequences clustered into 32 different alleles corresponding to 28 unique amino acid sequences and to 15 distinct hybridization patterns on this microarray. A collection of 78 clinical and veterinary isolates of Staphylococcus spp. was characterized using this assay. Nine of the 15 expected patterns, as well as one as-yet-unknown pattern, were identified. These patterns were detected in various epidemic methicillin-resistant Staphylococcus aureus strains, in S. pseudintermedius, and in coagulase-negative species such as S. epidermidis, S. fleurettii, or S. haemolyticus. There was no correlation between the different mecA hybridization patterns and the SCCmec type. Determination of MICs showed that mecA alleles corresponding to only four of these nine patterns were associated with β-lactam resistance. The mecA alleles that did not confer β-lactam resistance were largely restricted to coagulase-negative staphylococci of animal origin, such as S. sciuri and S. vitulinus. Because of the diversity of sequences and the different impact on β-lactam susceptibility, the existence of different mecA alleles needs to be taken into account when designing diagnostic assays for the detection of mecA.

The Anti-Repressor MecR2 Promotes the Proteolysis of the mecA Repressor and Enables Optimal Expression of β-lactam Resistance in MRSA

Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen, which is cross-resistant to virtually all β-lactam antibiotics. MRSA strains are defined by the presence of mecA gene. The transcription of mecA can be regulated by a sensor-inducer (MecR1) and a repressor (MecI), involving a unique series of proteolytic steps. The induction of mecA by MecR1 has been described as very inefficient and, as such, it is believed that optimal expression of β-lactam resistance by MRSA requires a non-functional MecR1-MecI system. However, in a recent study, no correlation was found between the presence of functional MecR1-MecI and the level of β-lactam resistance in a representative collection of epidemic MRSA strains. Here, we demonstrate that the mecA regulatory locus consists, in fact, of an unusual three-component arrangement containing, in addition to mecR1-mecI, the up to now unrecognized mecR2 gene coding for an anti-repressor. The MecR2 function is essential for the full induction of mecA expression, compensating for the inefficient induction of mecA by MecR1 and enabling optimal expression of β-lactam resistance in MRSA strains with functional mecR1-mecI regulatory genes. Our data shows that MecR2 interacts directly with MecI, destabilizing its binding to the mecA promoter, which results in the repressor inactivation by proteolytic cleavage, presumably mediated by native cytoplasmatic proteases. These observations point to a revision of the current model for the transcriptional control of mecA and open new avenues for the design of alternative therapeutic strategies for the treatment of MRSA infections. Moreover, these findings also provide important insights into the complex evolutionary pathways of antibiotic resistance and molecular mechanisms of transcriptional regulation in bacteria.

Enhanced surveillance of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in children in the UK and Ireland

ObjectiveTo determine the incidence and demographic features of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in children in the UK and Ireland and to characterise MRSA isolated from cases.DesignProspective surveillance study.SettingChildren aged...

‘Feral’ and ‘wild’-type methicillin-resistantStaphylococcus aureusin the United Kingdom

Circulation of methicillin-resistant Staphylococcus aureus (MRSA) outside hospitals could alter the impact of hospital-based control strategies. We investigated two groups of cases (each matched to controls with MRSA): 61 'community cases' not in acute hospital in the year before MRSA isolation; and 21 cases with ciprofloxacin-sensitive (CipS) MRSA. Multi-locus sequence typing, spa-typing and Panton-Valentine leukocidin gene testing were performed and demographics obtained. Additional questionnaires were completed by community case GPs. Community cases comprised 6% of Oxfordshire MRSA. Three community cases had received no regular healthcare or antibiotics: one was infected with CipS. Ninety-one percent of community cases had healthcare-associated sequence type (ST)22/36; CipS MRSA cases had heterogeneous STs but many had recent healthcare exposure. A substantial minority of UK MRSA transmission may occur outside hospitals. Hospital strains are becoming 'feral' or persisting in long-term carriers in the community with regular healthcare contacts; those with recent healthcare exposure may nevertheless acquire non-hospital epidemic MRSA strains in the community.

Single-nucleotide polymorphism in the SCCmec-orfX junction distinguishes between livestock-associated MRSA CC398 and human epidemic MRSA strains

A number of real-time PCR assays for direct detection of methicillinresistant (MRSA) in clinical specimens are targeting staphylococcal cassette chromosome mec (SCCmec) right extremity sequences and the S. aureus chromosomal orfX gene sequences located to the right of the SCCmec integration site. When testing 184 MRSA strains of human and animal origin from geographically distinct locations, we identified several characteristic single-nucleotide polymorphisms (SNPs) within the SCCmec-orfX junction of livestock-associated (LA) MRSA CC398 which serve as suitable strain markers for screening purposes. Within an assay time of 60 minutes and an additional 10 minutes for the melting curve analysis, all MRSA CC398 isolates were correctly identified by their characteristic T(m) value in the commercial LightCycler MRSA Advanced test. Studies to confirm the diagnostic accuracy of the SNP-based strain identification assay with a larger collection of clinical and LA-MRSA strains are ongoing.

Characterisation of MRSA from Malta and the description of a Maltese epidemic MRSA strain

Malta has one of the highest prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA) in Europe. However, only limited typing data are currently available. In order to address this situation, 45 MRSA isolates from the Mater Dei Hospital in Msida, Malta, were characterised using DNA microarrays. The most common strain was ST22-MRSA-IV (UK-EMRSA-15, 30 isolates). Sporadic strains included ST36-MRSA-II (UK-EMRSA-16, two isolates), PVL-positive ST80-MRSA-IV (European Clone, one isolate), ST228-MRSA-I (Italian Clone/South German Epidemic Strain, one isolate) and ST239-MRSA-III (Vienna/Hungarian/Brazilian Epidemic Strain, one isolate). Ten MRSA isolates belonged to a clonal complex (CC) 5/ST149, spa type t002 strain. This strain harboured an SCCmec IV element (mecA, delta mecR, ugpQ, dcs, ccrA2 and ccrB2), as well as novel alleles of ccrA/B and the fusidic acid resistance element Q6GD50 (previously described in the sequenced strain MSSA476, BX571857.1:SAS0043). It also carried the gene for enterotoxin A (sea) and the egc enterotoxin locus, as well as (in nine out of ten isolates) genes encoding the toxic shock syndrome toxin (tst1) and enterotoxins C and L (sec, sel). While the presence of the other MRSA strains suggests foreign importation due to travel between Malta and other European countries, the CC5/t002 strain appears, so far, to be restricted to Malta.

Usefulness of mec-associated direct repeat unit (dru) typing in the epidemiological analysis of highly clonal methicillin-resistant Staphylococcus aureus in Scotland

The incidence of the epidemic methicillin-resistant Staphylococcus aureus (EMRSA) strains EMRSA-15 and EMRSA-16 in Scotland has increased dramatically, now accounting for c. 70% and c. 20% of isolates, respectively. Epidemiological tracking of these EMRSA strains is difficult, as c. 50% of EMRSA-15 and c. 35% of EMRSA-16 isolates are indistinguishable using pulsed-field gel electrophoresis (PFGE) and other typing methods. The usefulness of mec-associated direct repeat unit (dru) sequence analysis as a more sensitive approach to tracking the persistence and spread of these 'clonal' EMRSA strains in Scotland was evaluated. Analysis of 47 EMRSA-15 and 57 EMRSA-16 isolates (including two separately cultured isolates of the Harmony collection type strain) obtained from 22 hospital laboratories over an 8-year period (1997-2005) revealed 13 and 12 different dru types, respectively. Whereas some types appeared to be endemic in multiple hospitals, subtypes that may represent specific strain movement among hospitals in a given geographical region were identified in other instances. These results suggest that mec-associated dru typing may have potential for identifying and tracking specific subtypes of otherwise indistinguishable epidemic MRSA isolates such as those in Scotland.

Are methicillin-resistant Staphylococcus aureus that produce Panton-Valentine leucocidin (PVL) found among residents of care homes?

Panton-Valentine leucocidin (PVL)-positive Staphylococcus aureus are responsible for causing skin and soft tissue infections, with the potential to cause severe invasive disease. Recently, methicillin-resistant Staphylococcus aureus (MRSA) strains that produce PVL have emerged in the community. As residents of care homes are a key group at risk of MRSA colonization and infection, we have examined the epidemiology of MRSA in three large cohorts of residents in urban care homes to establish whether PVL-positive MRSA strains are present in this setting. Nasal swabs (n = 3037) collected from consenting residents of 69 care homes in Leeds, UK, were screened for MRSA using chromogenic agar over three periods (June-August 2005, November-December 2006 and October-November 2007). PCR amplification was used to detect genes encoding PVL. Antibiogram profile and PFGE were also used to characterize MRSA isolates (n = 601). MRSA prevalence was 21%, 20% and 19% in each cohort, respectively. The majority of the isolates were related epidemiologically to the predominant local nosocomial epidemic MRSA strain, EMRSA-15 (78%). No isolate carried the genes encoding PVL. Twelve percent of the isolates (n = 74) had increased susceptibility to non-beta-lactam agents and were distributed across 31 care homes. MRSA strains that produced PVL were not found to be colonizing residents of care homes between 2005 and 2007. Continued surveillance is, however, necessary to understand the interaction between MRSA in care homes and hospitals, especially to reduce the chance that the former may amplify community-associated MRSA strains.

DNA microarray-based genotyping of methicillin-resistant Staphylococcus aureus strains from Eastern Saxony

A diagnostic microarray was used to characterise a collection of methicillin-resistant Staphylococcus aureus (MRSA) isolates from hospitals in the German region of Eastern Saxony. The most abundant epidemic MRSA (EMRSA) strains were ST5-MRSA II (Rhine-Hesse EMRSA, EMRSA-3), CC5/ST228-MRSA I (South German EMRSA), ST22-MRSA IV (Barnim EMRSA, EMRSA-15) and ST45-MRSA IV (Berlin EMRSA). Other strains were found only as sporadic isolates or in minor outbreaks. These strains included ST1-MRSA IV, ST8-MRSA IV (Hannover EMRSA and others), clonal group 5 strains carrying SCCmec type IV elements (Paediatric clone), ST45-MRSA V, CC8/ST239-MRSA III and ST398-MRSA V. Panton-Valentine leukocidin-positive MRSA isolates were still very rare. The predominant strain was ST80-MRSA IV, although increasing numbers of different strains have recently been detected (ST8-MRSA IV, ST30-MRSA IV and ST59-MRSA V). For more common MRSA strains, it was possible to detect variants that differed mainly in the carriage of additional resistance determinants and certain virulence-associated genes. Detection of such variants can sometimes allow epidemic strains to be resolved beyond spa types to a hospital-specific level, which is of significant value for epidemiological purposes.

Clonality of epidemic methicillin-resistant Staphylococcus aureus strains in Finland as defined by several molecular methods

In Finland, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) strains has increased ten fold within the last decade. In order to follow the changing epidemiology of MRSA, accurate typing of S. aureus strains is important. The purpose of this study was to reanalyse 44 previously recognised Finnish epidemic MRSA strains (EMRSA) by several molecular typing methods and to revise their nomenclature. The 44 EMRSA strains were grouped into 26 pulsed-field gel electrophoresis (PFGE) clusters, 20 multi locus sequence typing (MLST) sequence types (ST) belonging to 12 clonal complexes (CC) of which CC8 was the most prevalent, and 27 spa types belonging to four clonal complexes. The staphylococcal cassette chromosome mec (SCCmec) type IV was predominant, and 48% of the strains were nonmultiresistant to antibiotics. The discriminatory power of PFGE clusters, MLST, and spa typing was high. The overall concordance values of typing methods differed when assessed by two different methods. Adjusted Rand coefficient provided fairly low correlations for all comparisons. However, spa type was able to efficiently predict types and clonal complexes of most of the other methods with high probability (> or =80%).

Amoebae promote persistence of epidemic strains of MRSA

The control of healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) infection is of concern worldwide. Given the evidence that several pathogenic species replicate within amoebae and emerge more virulent and more resistant and the abundance of amoebae in healthcare settings, we investigated interactions of Acanthamoeba polyphaga with epidemic MRSA isolates. MRSA proliferated in the presence of amoebae, attributable partly to intracellular replication. Following 24 h of co-culture, confocal microscopy revealed that c. 50% amoebae had viable MRSA within phago-lysosomes and 2% of amoebae were heavily infected with viable cocci throughout the cytoplasm. Infection control strategies should recognize the contribution of protozoa.

Use of Variations in Staphylococcal Interspersed Repeat Units for Molecular Typing of Methicillin-Resistant Staphylococcus aureus Strains

Staphylococcal interspersed repeat unit typing has previously been shown to have the ability to discriminate between epidemic methicillin-resistant Staphylococcus aureus strains in the United Kingdom. The current study illustrates its ability to distinguish between strains within an endemic setting thereby providing a rapid transportable typing method for the identification of transmission events.

Prevalence of methicillin-resistant Staphylococcus aureus among staff and pets in a small animal referral hospital in the UK

The occurrence of methicillin-resistant Staphylococcus aureus (MRSA) and the possible relatedness between human and animal isolates were investigated among veterinary staff and hospitalized animals in a referral small animal hospital in the UK. A total of 300 swab samples were taken from nasal and oral mucosae of 78 veterinary staff, 45 dogs, 12 cats and from 30 environmental surfaces. Staphylococci were isolated by selective enrichment and characterized by biochemical tests and antimicrobial disc susceptibility testing. MRSA isolates were genotypically confirmed by PCR and typed by PFGE. MRSA was isolated from 14 staff (17.9%), four dogs (9%), and three environmental sites (10%) yielding a total of 28 MRSA isolates. PFGE analysis revealed that most MRSA isolates were indistinguishable (56%) or closely related (26%) to EMRSA-15, one of the two epidemic MRSA strains dominant in UK hospitals. Like EMRSA-15, the predominant strain isolated from staff, dogs and environmental sites was resistant to fluoroquinolones in addition to all beta-lactams. The study provides evidence of EMRSA-15 mucosal carriage in veterinary staff and hospitalized dogs, with the risk of MRSA carriage in veterinary staff being significantly higher than reported for the UK healthy community. EMRSA-15 was predominant in the hospital environment, including humans, dogs, and inanimate objects, but the mode by which the strain was introduced and spread remains uncertain.

Characterization of isolates of methicillin-resistant Staphylococcus aureus from Hong Kong by phage typing, pulsed-field gel electrophoresis, and fluorescent amplified-fragment length polymorphism analysis.

The genetic relatedness of 127 methicillin-resistant Staphylococcus aureus (MRSA) isolates, belonging to five major types as identified by pulsed-field gel electrophoresis (PFGE) and antibiotic resistance profiles, was examined further using phage typing and fluorescent amplified fragment length polymorphism (FAFLP). The MRSA isolates were recovered from patients at the Prince of Wales Hospital (PWH), Hong Kong, over a 13-year period, 1988 to 2000. These strains were also compared with representatives of the well-described MRSA international clones and with epidemic MRSA strains (eMRSA) 1 to 16 from the United Kingdom. Phage typing distinguished two major "clones" at this hospital: all of the phage type 1 (PT1) isolates belonged to PFGE types A, C, D, and E, while most of the PT2 isolates were associated with PFGE type B, which exhibited a unique antibiotic resistance profile. MRSA isolates belonging to PFGE subtype A2 were indistinguishable from the British eMRSA-1, while isolates of PFGE type B were closely related to eMRSA-9 by PFGE. Based on FAFLP, all five predominant PFGE types at the PWH belonged to one group and fell into the same cluster as eMRSA-1, -4, -7, -9, and -11 isolates. Multilocus sequence typing and staphylococcal cassette chromosome mec typing classified representatives of our MRSA isolates as members of the same clone (ST239-MRSA-III). Thus, the predominant MRSA isolates frin the PWH in the last decade are closely related to early United Kingdom eMRSA clones 1, 4, and 11 and are members of a lineage that includes the Brazilian MRSA clone.

Relationship between molecular epidemiology and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) in a French teaching hospital.

The objective of this study was to investigate the relationship between molecular epidemiology and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) over a period of 4 years. The antibiotype of all MRSA isolates that were identified during a yearly period of 3 months was determined; 50 consecutive non-replicate MRSA isolates were typed each year. Susceptibility rates to gentamicin, tobramycin and ofloxacin remained stable (95, 16 and 4 %, respectively). In contrast, the proportion of MRSA isolates susceptible to erythromycin increased progressively from 10.5 to 32.5 % (P < 0.001). PFGE analysis of genomic DNA from 200 isolates revealed the presence of 15 different clones. Two epidemic clones were identified, which contained 150 (clone A) and 28 (clone C) isolates. Non-epidemic strains were more frequently susceptible to ofloxacin (31.8 versus 1.1 %) and tobramycin (45.4 versus 16.8 %) than epidemic strains; those isolates that were susceptible to all antibiotics tested belonged to sporadic clones. The increase of erythromycin susceptibility within MRSA isolates was caused by the emergence of clone C. This study suggests that when selection pressure exerted by an antibiotic is insufficient (i.e. below a threshold level), fitness advantages play a predominant role in the dissemination of MRSA clones. The balance between the selection pressure exerted by antibiotics and the disadvantage of lower replication rates of resistant strains in the absence of antibiotics complicates the biological model of clonal dissemination of epidemic MRSA strains.