Reduced nephrotoxicity with vancomycin therapeutic drug monitoring guided by area under the concentration-time curve against a trough 15-20 μg/mL concentration

Abstract

Vancomycin is often employed as an antibacterial agent against Gram-positive bacteria, although dose-dependent nephrotoxicity is a concern. Although the risk may be reduced by therapeutic drug monitoring (TDM) guided by area under the concentration-time curve (an attempt to target an AUC > 400 μg•h/mL by Bayesian prediction: AUC₄₀₀-guided TDM), the clinical efficacy of AUC₄₀₀-guided TDM compared with trough concentration-guided TDM within 15-20 μg/mL (Trough_15-20-guided TDM) has yet to be determined. We aimed to retrospectively evaluate the difference in the incidence rate of acute kidney injury (AKI), classified according to the Acute Kidney Injury Network, between these TDM groups. Individual AUC in the AUC₄₀₀-guided TDM group was calculated by Bayesian prediction using trough and peak concentrations (within 3 h after the end of infusion). The AKI incidence in the Trough_15-20-guided TDM group was 28.8% (15/52 patients) compared with an AKI incidence in the AUC₄₀₀-guided TDM group of 9.1% (2/22 patients). Application of AUC₄₀₀-guided TDM was identified as an independent factor for avoiding the incidence of AKI by Cox hazard regression analysis [hazard ratio = 0.168, 95% confidence interval (CI) 0.034-0.839] and logistic regression analysis (odds ratio = 0.037, 95% CI 0.003-0.285). As the estimated glomerular filtration rate (eGFR) improved, the surrogate target trough concentration for an AUC > 400 μg•h/mL was lowered (intercept 15.0074, slope -0.0598). In conclusion, AUC₄₀₀-guided TDM may be superior to Trough_15-20-guided TDM for the reduction of nephrotoxicity during vancomycin therapy.

Keywords: AUC; Area under the concentration–time curve; Nephrotoxicity; Therapeutic drug monitoring; Vancomycin.