Evaluation of a trough-only extrapolated area under the curve vancomycin dosing method on clinical outcomes

BackgroundVancomycin dosing strategies targeting trough concentrations of 15-20 mg/L are no longer supported due to lack of efficacy evidence and increased risk of nephrotoxicity. Area-under-the-curve (AUC(24)) nomograms have demonstrated adequate attainment of AUC(24)goals >= 400 mg h/L with more conservative troughs (10-15 mg/L).ObjectiveThe purpose of this study is to clinically validate a vancomycin AUC(24)dosing nomogram compared to conventional dosing methods with regards to therapeutic failure and rates of acute kidney injury.SettingThis study was conducted at a tertiary, community, teaching hospital in the United States.MethodThis retrospective, cohort study compared the rates of therapeutic failures between AUC(24)-extrapolated dosing and conventional dosing methods.Main outcome measurePrimary outcome was treatment failure, defined as all-cause mortality within 30 days, persistent positive methicillin-resistantStaphylococcus aureusblood culture, or clinical failure. Rates of acute kidney injury in non-dialysis patients was a secondary endpoint.ResultsThere were 96 participants in the extrapolated-AUC(24)cohort and 60 participants in the conventional cohort. Baseline characteristics were similar between cohorts. Failure rates were 11.5% (11/96) in the extrapolated-AUC(24)group compared to 18.3% (11/60) in the conventional group (p = 0.245). Reasons for failure were 6 deaths and 5 clinical failures in the extrapolated-AUC(24)cohort and 10 deaths and 1 clinical failure in the conventional group. Acute kidney injury rates were 2.7% (2/73) and 16.4% (9/55) in the extrapolated-AUC(24)and conventional cohorts, respectively (p = 0.009).ConclusionExtrapolated-AUC(24)dosing was associated with less nephrotoxicity without an increase in treatment failures for bloodstream infections compared to conventional dosing. Further investigation is warranted to determine the relationship between extrapolated-AUC(24)dosing and clinical failures.