Are vancomycin troughs adequate for optimal dosing?
Antimicrob Agents Chemother. 2013 Oct 28;
Authors: Neely MN, Youn G, Jones B, Jelliffe RW, Drusano GL, Rodvold KA, Lodise TP
The current vancomycin therapeutic guidelines recommend to only use trough concentrations to manage dosing in adults with Staphylococcus aureus infections. Both vancomycin efficacy and toxicity are likely related to the area under the plasma time-concentration curve (AUC). We assembled richly sampled vancomycin pharmacokinetic data from three studies comprising 47 adults with varying renal function. With Pmetrics, the non-parametric population modeling package for R, we compared AUCs estimated from models derived from trough-only and peak-trough depleted versions of the full dataset and characterized the relationship between vancomycin trough and AUC. Trough-only and peak-trough depleted datasets underestimated true AUCs compared to the full model by a mean (95% CI) of 23% (11% - 33%, P=0.0001) and 14% (7% - 19%, P<0.0001), respectively. In contrast, using the full model as a Bayesian prior with trough-only data allowed 97% (93% - 102%, P=0.23) accurate AUC estimation. Based on 5000 profiles simulated from the full model, among adults with normal renal function and a therapeutic AUC ≥400 mg*h/L for an organism with a vancomycin minimum inhibitory concentration (MIC) of 1 mg/L, approximately 60% are expected to have a trough concentration below the suggested minimum target of 15 mg/L for serious infections, which could result in needlessly increased doses and risk of toxicity. Our data indicate adjusting vancomycin doses based on trough concentrations without a Bayesian tool results in poor achievement of maximally safe and effective plasma exposures, and that many adults can have an adequate vancomycin AUC with a trough <15 mg/L.
PMID: 24165176 [PubMed - as supplied by publisher]