Vancomycin 24-Hour Area under the Curve/Minimum Bactericidal Concentration Ratio as a Novel Predictor of Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia

Abstract

ABSTRACT While previous studies have examined the association between vancomycin (VAN) exposure and MIC with regard to outcomes in methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B), none have explored if a relationship exists with the VAN minimum bactericidal concentration (MBC). The objective of this study was to evaluate the VAN 24-h area under the curve (AUC 24 )/MBC ratio as a pharmacodynamic predictor of mortality. This retrospective cohort study included patients treated with VAN for MRSA-B with the primary outcome of 30-day all-cause mortality. Data collected included patient demographics, comorbidities, antimicrobial treatment data, therapeutic drug levels, and laboratory and microbiological data. Vancomycin MICs and MBCs were determined by Etest (MIC only) and broth microdilution (BMD). The vancomycin AUC 24 was determined by pharmacokinetic maximum a posteriori probability Bayesian (MAP-Bayesian) analysis. The most significant breakpoint for 30-day mortality was determined by classification and regression tree (CART) analysis. The association between pharmacodynamic parameters (VAN AUC 24 /MIC BMD , VAN AUC 24 /MIC Etest , and AUC 24 /MBC BMD ) and mortality were determined by χ 2 and multivariable Poisson regression. Overall mortality in this cohort ( n = 53) was 20.8% ( n = 11/53), and all corresponding MRSA blood isolates were VAN susceptible (MIC range, 0.5 to 2 μg/ml; MIC 50 , 1 μg/ml; MIC 90 , 1 μg/ml). The CART-derived breakpoints for mortality were 176 (VAN AUC 24 /MBC) and 334 (VAN AUC 24 /MIC BMD ). In multivariable analysis, the association between a VAN AUC 24 /MBC of ≥176 and survival persisted, but VAN AUC 24 /MIC BMD values (≥334 or ≥400) were not associated with improved mortality. In conclusion, VAN AUC 24 /MBC was a more important predictor of 30-day mortality than VAN AUC 24 /MIC for MRSA-B.