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

Background Vancomycin 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 (AUC₂₄) nomograms have demonstrated adequate attainment of AUC₂₄ goals ≥ 400 mg h/L with more conservative troughs (10-15 mg/L). Objective The purpose of this study is to clinically validate a vancomycin AUC₂₄ dosing nomogram compared to conventional dosing methods with regards to therapeutic failure and rates of acute kidney injury. Setting This study was conducted at a tertiary, community, teaching hospital in the United States. Method This retrospective, cohort study compared the rates of therapeutic failures between AUC₂₄-extrapolated dosing and conventional dosing methods. Main outcome measure Primary outcome was treatment failure, defined as all-cause mortality within 30 days, persistent positive methicillin-resistant Staphylococcus aureus blood culture, or clinical failure. Rates of acute kidney injury in non-dialysis patients was a secondary endpoint. Results There were 96 participants in the extrapolated-AUC₂₄ cohort and 60 participants in the conventional cohort. Baseline characteristics were similar between cohorts. Failure rates were 11.5% (11/96) in the extrapolated-AUC₂₄ 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-AUC₂₄ 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-AUC₂₄ and conventional cohorts, respectively (p = 0.009). Conclusion Extrapolated-AUC₂₄ 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-AUC₂₄ dosing and clinical failures.