Optimizing outcomes using vancomycin therapeutic drug monitoring in patients with MRSA bacteremia: trough concentrations or area under the curve?

Abstract

Background: Vancomycin therapeutic drug monitoring is routinely performed but the specific measure used in practice is variable.

Objective: To evaluate the relationship between the first measured vancomycin trough, area-under-the-curve (AUC), and failure in patients with MRSA bacteremia.

Methods: This retrospective, cohort study included adult non-neutropenic patients with MRSA bacteremia who received vancomycin. The primary outcome was treatment failure. Initial trough and AUC values were compared between the failure and success groups. Classification and regression tree analysis was used to identify thresholds associated with failure. Multivariate analysis was performed to control for identified confounders.

Results: There were 89 patients. Failure occurred in 23 (26%). Trough and AUC values associated with failure were < 10.6 mg/L (39% vs. 13%; P = 0.006) and AUC < 410mg*h/L (40% vs. 17%; P = 0.014). Both remained significant after controlling covariates (trough < 10.6 mg/L, OR [95% CI] = 4.91 [1.6-15]; AUC<410mg*h/L, OR [95% CI] = 3.13 [1.14-8.62]). Only AUC was predictive of nephrotoxicity.

Conclusion: Failure was more common with troughs < 10.6 mg/L or AUC < 410 mg*h/L. Supratherapeutic AUCs, but not trough, were associated with nephrotoxicity.

Keywords: Bacteremia; Drug monitoring; Methicillin-resistant Staphylococcus aureus; Vancomycin.