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Vancomycin 24-hour area under the curve (AUC24)/minimum bactericidal concentration (MBC) ratio as a novel predictor of mortality in methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B).
Antimicrob Agents Chemother. 2016 Mar 7;
Authors: Britt NS, Patel N, Horvat RT, Steed ME
Abstract
While previous studies have examined the association between vancomycin (VAN) exposure and minimum inhibitory concentration (MIC) with regard to outcomes in methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B), none have explored if a relationship exists with VAN minimum bactericidal concentration (MBC). The objective of this study was to evaluate the VAN 24 h area under the curve (AUC24)/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, laboratory, and microbiological data. Vancomycin MICs and MBCs were determined by Etest (MIC only) and broth microdilution (BMD). Vancomycin AUC24 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 AUC24/MICBMD, VAN AUC24/MICEtest, and AUC24/MBCBMD) 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 - 2 μg/mL; MIC50, 1 μg/mL; MIC90, μg/mL). The CART-derived breakpoints for mortality were 176 (VAN AUC24/MBC) and 334 (VAN AUC24/MICBMD). In multivariable analysis, the association between VAN AUC24/MBC ≥ 176 and survival persisted, but VAN AUC24/MICBMD (≥ 334 or ≥ 400) were not associated with improved mortality. In conclusion, VAN AUC24/MBC was a more important predictor of 30-day mortality than VAN AUC24/MIC for MRSA-B.
PMID: 26953202 [PubMed - as supplied by publisher]