The dosing and monitoring of vancomycin: what is the best way forward?

Abstract

We have evaluated the literature to review optimal dosing and monitoring of intravenous vancomycin in adults, in response to evolving understanding of targets associated with efficacy and toxicity. The area under the total concentration-time curve (0-24 h) divided by the minimum inhibitory concentration (AUC₂₄/MIC) is the most commonly accepted index to guide vancomycin dosing for the treatment of Staphylococcus aureus infections, with a value of 400 h a widely recommended target for efficacy. Upper limits of AUC₂₄ exposure of around 700 (mg/L).h have been proposed, based on the hypothesis that higher exposures of vancomycin are associated with an unacceptable risk of nephrotoxicity. If AUC₂₄/MIC targets are used, sources of variability in the assessment of both AUC₂₄ and MIC need to be considered. Current consensus guidelines recommend measuring trough vancomycin concentrations during intermittent dosing as a surrogate for the AUC₂₄. Trough concentrations are a misleading surrogate for AUC₂₄ and a poor end-point in themselves. AUC₂₄ estimation using log-linear pharmacokinetic methods based on two plasma concentrations, or Bayesian methods are superior. Alternatively, a single concentration measured during continuous infusion allows simple AUC₂₄ estimation and dose-adjustment. All of these methods have logistical challenges which must be overcome if they are to be adopted successfully.

Keywords: Drug monitoring; Pharmacokinetics; Staphylococcus aureus; Vancomycin.