In Vitro Cytotoxicity and Clinical Correlates of MRSA Bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections are associated with significant morbidity and mortality. MRSA secretes a number of virulence factors and pore-forming toxins that enable tissue invasion. Prior studies have found associations between decreased toxin production and poor outcomes in invasive MRSA infection, particularly in pneumonia. In this retrospective observational cohort study of MRSA bacteremia in adult patients from 2007 to 2015, we examined whether cytotoxicity was associated with 30-day mortality. Isolates were obtained from 776 patients and screened for cytotoxicity in a human HL-60 cell model, antimicrobial susceptibility, and spa type, and clinical data were abstracted from charts. We did not find an association between low cytotoxic activity and 30-day mortality in univariate logistic regression analyses. There was a difference in distribution of the genotypes across cytotoxicity phenotypes, with spa-CC008 accounting for a larger proportion of isolates in the high cytotoxicity group. Isolates with a skin and soft tissue primary infective site had a higher median cytotoxicity. There was no association between cytotoxicity and host factors such as age or comorbidity burden. The isolates in our study came from heterogeneous primary sites of infection and were predominantly from spa-CC002 and spa-CC008 lineages, so it is possible that findings in prior studies reflect a different distribution in genotypes and clinical syndromes. Overall, in this large study of cytotoxicity of MRSA bloodstream isolates, we did not find the low cytotoxicity phenotype to be predictive of poor outcomes in MRSA bacteremia.