Abstract
•Vancomycin remains an indispensable agent for the treatment of S. aureus infections.•Therapeutic drug monitoring can maximise the probability of successful outcomes.•Bayesian and log-linear methods or continuous infusions are superior to trough monitoring.•Variation in estimates of drug exposure and pathogen susceptibility must be considered for rational treatment individualization.
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.