Panton-Valentine leukocidin (PVL), encoded by the lukSF-PV genes, is a putative virulence factor and marker for communityassociated methicillin-resistant Staphylococcus aureus. Here we report the prevalence of PVL among a representative sample of 1,055 S. aureus infection isolates from the United States and describe the sequence variation of the lukSF-PV genes. We performed multilocus sequence typing (MLST) on all isolates and sequenced fragments of the lukSF-PV genes from a sample of 86 isolates. We assigned isolates to a PVL R or H sequence type based on a polymorphism that results in an amino acid change from arginine (R) to histidine (H). Overall, we found that 36% of S. aureus isolates were positive for lukSF-PV. Among the 86 we typed, we identified 72 R variants and 14 H variants. Among the 47 methicillin-resistance S. aureus (MRSA) isolates, 43 harbored the R variant, and among the 39 methicillin-susceptible S. aureus (MSSA) isolates, 29 harbored the R variant. Almost all (97%) of the R variants were found in MLST clonal complex 8 (CC8), while the H variant was broadly distributed among 6 CCs. Within CC8, all 38 MRSA (USA300) and all 28 MSSA isolates harbored the R variant. Of the 20 isolates from blood and the lower respiratory tract, 19 (95%) harbored the R variant. While the R variant had been linked primarily to USA300 MRSA, we found that all CC8 MSSA isolates also contained the R variant, suggesting that some strains of USA300 may have lost methicillin resistance as an adaptation in the community.
To assess the clonal structure of Staphylococcus aureus in the United States, we performed a molecular epidemiological study of 1,055 S. aureus isolates from a nationally representative clinical isolate collection from 2004-2008. Resistant and susceptible isolates were typed with multilocus sequence typing, tested for the presence of Panton-Valentine leukocidin (PVL), and serotyped. USA300 (multilocus sequence typing clonal complex 8, PVL positive, and methicillin-resistant) was the most frequently isolated clone, expanding from 12% of all isolates in 2004 to 38% in 2006. The USA300 clone increased significantly in frequency among both outpatients and inpatients. USA300 increased in both skin and soft-tissue and invasive infection isolates. The second most frequently observed clone was clonal complex 5, PVL-negative, and methicillin-resistant, and its frequency was stable from 2004-2008. The methicillin-susceptible S. aureus in the study was polyclonal, and decreased in frequency as it was replaced by USA300.
SUMMARY
There are limited data examining whether outcomes of MRSA healthcare-associated infections (HAIs) are worse when caused by community-associated strains compared to healthcare-associated strains. We reviewed all patient charts at our institution from 1999 to 2009 that had MRSA first isolated only after 72 hours of hospitalization (n=724). Of these, 384 patients had an MRSA-HAI by CDC criteria. Treatment failure was similar in those infected with a phenotypically CA-MRSA strain compared to a phenotypically HA-MRSA strain (23% vs. 15%, P=0.10) as was 30-day mortality (16% vs. 19%, P=0.57). Independent risk factors associated with (p<0.05) treatment failure were higher Charlson Comorbidity Index, higher APACHE II score, and no anti-MRSA treatment. These factors were also associated with 30-day mortality, as were female gender, older age, MRSA bloodstream infection, MRSA pneumonia, and HIV. Our findings suggest that clinical and host factors, not MRSA strain type, predict treatment failure and death in hospitalized patients with MRSA-HAIs.
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