title: Vancomycin 24-Hour Area under the Curve/Minimum Bactericidal Concentration Ratio as a Novel Predictor of Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia.
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 (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, and laboratory and microbiological data. Vancomycin MICs and MBCs were determined by Etest (MIC only) and broth microdilution (BMD). The 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 to 2 μg/ml; MIC50, 1 μg/ml; MIC90, 1 μg/ml). The CART-derived breakpoints for mortality were 176 (VAN AUC24/MBC) and 334 (VAN AUC24/MICBMD). In multivariable analysis, the association between a VAN AUC24/MBC of ≥176 and survival persisted, but VAN AUC24/MICBMD values (≥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.
authors.affiliation: Department of Pharmacy Practice, University of Kansas School of Pharmacy, Lawrence, Kansas, USA.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Britt
authors.affiliation: Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: Nimish
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kansas School of Medicine, Kansas City, Kansas, USA.
authors.forename: Rebecca T
authors.initials: RT
authors.lastname: Horvat
authors.affiliation: Department of Pharmacy Practice, University of Kansas School of Pharmacy, Lawrence, Kansas, USA msteed@kumc.edu.
authors.forename: Molly E
authors.initials: ME
authors.lastname: Steed
mesh_terms: D000367:Age Factors; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D014640:Vancomycin / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin