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Infective endocarditis due to methicillin-resistantStaphylococcus aureus (MRSA IE) is associated with high morbidity and mortality. Vancomycin continues to be the primary treatment for this disease. The emergence of heterogeneous vancomycin-intermediateStaphylococcus aureus (hVISA), defined as a modified population analysis profile (PAP) of ≥0.9, may affect patient outcomes. The objective of this study was to evaluate the relationship of vancomycin subpopulation susceptibility and the clinical outcomes of MRSA IE. We conducted a retrospective cohort study of patients treated with vancomycin for MRSA IE from 2002 to 2013 at the Detroit Medical Center. A modified PAP was used to measure the vancomycin PAP MIC and the PAP-to-area under the curve (AUC) ratio. Treatment failure was defined as bacteremia for ≥7 days or death attributed to MRSA. Classification and regression tree (CART) analysis was used to select a failure breakpoint between the PAP-AUC ratios and the PAP MIC. A total of 202 patients were included in the study. Twenty-seven percent of the patients had left-sided IE, 19% of the strains were hVISA, and 70% of the strains were staphylococcal cassette chromosomemec element (SCCmec ) type IV. Overall treatment failure was observed in 64%; 59% had persistent bacteremia, and the 30-day attributable mortality rate was 21%. The CART breakpoint between failure and success in terms of the PAP-AUC ratio was 0.9035. On logistic regression analysis, intensive care unit (ICU) admission (adjusted odds ratio [aOR], 2.8; 95% confidence interval [CI], 1.5 to 5.2) and a PAP MIC of ≥4 mg/liter (aOR, 3.2; 95% CI, 1.3 to 8.4) were associated with failure (P = 0.001 and 0.015, respectively). A PAP MIC of ≥4 mg/liter and ICU admission were significant for treatment failure for patients with MRSA IE. The PAP-AUC ratio of ≥0.9035 predicted failure consistent with the hVISA definition. The role of population MIC analysis in predicting outcome with MRSA infections warrants further investigation.

antimicrobial agents and chemotherapy

Evaluation of Vancomycin Population Susceptibility Analysis Profile as a Predictor of Outcomes for Patients with Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus