Methicillin-Resistant Staphylococcus aureus Bacteremia Treated With Vancomycin Calculated by Area-Under-the-Curve in Patients With Elevated Vancomycin Minimum Inhibitory Concentrations

Abstract

Purpose: Vancomycin is recommended as first-line treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, dosed by area-under-the-curve (AUC) with an assumed minimum inhibitory concentration (MIC) of 1 mcg/mL via broth microdilution. The purpose of this study was to compare effectiveness of AUC-based and trough-based dosing in MRSA bacteremia with an MIC > 1 mcg/mL via Etest. Methods: This was a retrospective, observational cohort that compared vancomycin dosed by AUC or trough between January 1, 2017 and September 1, 2022. The primary outcome was a composite of treatment failure defined as peristent bacteremia ≥ 7 days, inpatient mortality within 90 days, or microbiologic relapse or readmission within 30 days. Secondary outcomes compared nephrotoxicity, hospital and ICU length of stay, MIC differences, and difference in exposure measured by AUC. Results: Twenty-four patients in each group met inclusion criteria. For the primary outcome, there was no statistical difference in treatment failure between trough and AUC groups, respectively [10 (41.7%) vs 10 (41.7%), P = 1.000]. There was no statistical difference in secondary outcomes, with incidence of nephrotoxicity [3 (12.5%) trough vs 2 (8.33%) AUC, P = 1.000] and median AUC exposure over treatment course [502.9 mcg.h/mL (454.1-599.9) vs 474 mcg.h/mL (435.3-533), P = .312] similar between groups. Conclusion: There was no statistically significant difference in treatment failure for vancomycin by AUC or trough with an Etest MIC > 1 mcg/mL. Overall exposure to vancomycin and incidence of nephrotoxicty were numerically higher in the trough group, suggesting that dosing by AUC may limit exposure without impact on treatment failure.