Abstract
Background: Chronic kidney disease (CKD) patients requiring intravenous vancomycin bear considerable risks of adverse outcomes both from the infection and vancomycin therapy itself, necessitating especially precise dosing to avoid sub- and supratherapeutic vancomycin exposure. Methods: In this retrospective study, we performed a population pharmacokinetic analysis to construct a vancomycin dose prediction model for CKD patients who do not require renal replacement therapy. The model was externally validated on an independent cohort of patients to assess its prediction accuracy. The pharmacokinetic parameter estimates and the equations were productized into a Web application (VancApp) subsequently implemented in routine care. The association between VancApp-based dosing and time-to-target concentration attainment, 30-day mortality, and nephrotoxicity were assessed postimplementation. Results: The model constructed from an initial cohort (n = 80) revealed a population clearance and volume of distribution of 1.30 L/h and 1.23 L/kg, respectively. External model validation (n = 112) demonstrated a mean absolute prediction error of 1.25 mg/L. Following 4 months of clinical implementation of VancApp as an optional alternative to usual care [VancApp (n = 22) vs. usual care (n = 21)], patients who had received VancApp-based dosing took a shorter time to reach target concentrations (median: 66 vs. 102 h, p = 0.187) and had fewer 30-day mortalities (14% vs. 24%, p = 0.457) compared to usual care. While statistical significance was not achieved, the clinical significance of these findings appear promising. Conclusion: Clinical implementation of a population pharmacokinetic model for vancomycin in CKD can potentially improve dosing precision in CKD and could serve as a practical means to improve vital clinical outcomes.
Highlights
Treatment success with intravenous vancomycin hinges on timely and accurate attainment of target drug exposure (Hidayat et al, 2006; Martinez et al, 2012)
Clinical Impact Assessment To assess the impact of vancomycin dosing application (VancApp)-based dosing, we retrospectively reviewed patients who received vancomycin from November 2016 to February 2017
The derivation cohort comprised of 80 patients who had a mean ± standard deviation (SD) creatinine clearance (CrCl) of 33.8 ± 10.3 ml/min and total body weight (TBW) of 57.8 ± 15.7 kg
Summary
Treatment success with intravenous vancomycin hinges on timely and accurate attainment of target drug exposure (Hidayat et al, 2006; Martinez et al, 2012). Chronic kidney disease (CKD) alters both the volume of distribution (Vd) and clearance of vancomycin, predisposing patients to dosing inaccuracies which lead to delayed target exposures (Jeffres et al, 2007; Matzke et al, 2011). Precise dosing plays a pivotal role in maximizing treatment success in CKD patients requiring intravenous vancomycin. Chronic kidney disease (CKD) patients requiring intravenous vancomycin bear considerable risks of adverse outcomes both from the infection and vancomycin therapy itself, necessitating especially precise dosing to avoid sub- and supratherapeutic vancomycin exposure
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