So what is CaMRSA? An acceptable working definition is a methicillin-resistant S. aureus infection occurring in a patient without a history of healthcare risk factors due to an isolate carrying SCCmecA type IV. The isolate is also likely to express the PVL virulence factor. This definition combines what is known about both the clinical and molecular epidemiology of these strains. Further research and time is likely to result in modifications to our understanding of this emerging phenomenon.
Antibiotic Susceptibility Patterns
CaMRSA strains have unique susceptibility patterns compared with traditional MRSA strains. As noted above, SCCmecA codes for methicillin resistance in S. aureus. SCCmecA types II and III are large genetic elements that usually code for resistance to multiple antibiotics. In contrast, type IV is smaller and results in decreased susceptibility to betalactams alone. CaMRSA strains are identifiable as being susceptible to clindamycin, trimethoprim-sulfamethoxazole, and the aminoglycosides (4). Susceptibility to clindamycin must be interpreted cautiously in strains that are erythromycin resistant. If erythromycin resistance is due to an inactivating enzyme (a ribosomal methylase) resistance to clindamycin can be induced. This macrolide-lincosamide-streptogramin–inducible phenotype can be identified in the microbiology lab by performing an erythromycin induction test (D-test). Clinical failures have been described when clindamycin has been used in the presence of this inducible phenotype (10).
Outbreaks
As with many infectious diseases, outbreaks first brought the problem of CaMRSA to wider attention. The first well-described outbreak occurred in the early 1980s among intravenous drug users in Detroit (11). Reports in the early 1990s focused on MRSA infections in young children without risk factors for resistant infection (12). Overwhelming, fatal sepsis due to MRSA was described in 4 pediatric patients in Minnesota and North Dakota. A fulminant, necrotizing pneumonia characterized 3 of the cases (13). Subsequently numerous outbreaks have been described among prison inmates, sexual partners, and competitive sports participants (14-16).
Two well-documented outbreaks have been described in football players. Begier and colleagues identified an outbreak that involved 10 players on the same college football team. Molecular typing demonstrated all recovered isolates to be of the same strain and to carry SCCmecA and the PVL gene. The case-control analysis showed an association between infection and playing wide receiver or cornerback, turf burns, and body shaving (17). An investigation of 8 MRSA infections among professional football players similarly showed all recovered strains to be clonal and to harbor SCCmecA IV and the PVL locus. In contrast to the college outbreak, these investigators found an association between being a lineman or a linebacker and disease. Turf burns were again a significant risk factor (18).
Both of these outbreaks, although geographically separate, were found to be due to the same strain of MRSA, clone USA300-0114. This clone has also been demonstrated as the predominant cause of CaMRSA in other communities (15,19). This would seem to indicate greater fitness of this particular strain that has allowed it to spread widely (20).
Clinical Manifestations
In general, CaMRSA has been reported to cause a similar spectrum of disease as methicillin-susceptible S. aureus (MSSA). As mentioned above, it appears to be seen mostly in otherwise healthy, young individuals. In the population based surveillance project of Fridkin et al., 77% of patients with community MRSA had skin and soft tissue infections (9). Invasive disease was observed in 6%. Similarly, Naimi and colleagues found skin and soft tissue infections in 75% of the subjects in their study of community-associated MRSA in Minnesota (21).
There is concern that CaMRSA may be associated with a greater likelihood of disease compared with other S. aureus strains. Ellis et al. prospectively evaluated active-duty soldiers found to be colonized with CaMRSA. Of the 24 colonized, 38% or 9 individuals developed soft-tissue infections as compared with 3% of those colonized with MSSA. Eight of nine affected patients had abscesses. All 9 of the available clinical isolates were positive for the PVL gene and the presence of this virulence factor was associated with an increased risk of invasive disease (22). Other authors have found an association between PVL-carrying strains of S. aureus and disease and it is perhaps this characteristic, not methicillin resistance, that assists the organism in causing disease in otherwise healthy individuals (23,24). The observed high prevalence of the PVL virulence factor among CaMRSA has been described as the “convergence of resistance and virulence” (25).