Int J Antimicrob Agents. 2020 Jul 25:106109. doi: 10.1016/j.ijantimicag.2020.106109. Online ahead of print.
Vancomycin has often been employed as an antibacterial agent against gram-positive bacteria, though dose-dependent nephrotoxicity has been concerned. Although the risk may be reduced by therapeutic drug monitoring 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 to that of trough concentration-guided TDM within 15-20 μg/mL (Trough15-20-guided TDM), has yet to be determined. We aimed to retrospectively evaluate the difference in the incidence rate of acute kidney injury (AKI, classified by 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). An AKI incidence in the Trough15-20-guided TDM group was 28.8% (15/52 patients). While, an AKI incidence in the AUC400-guided TDM group was 9.1 % (2/22 patients). The application of the 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 Trough15-20 guided TDM for the reduction of nephrotoxicity during vancomycin therapy.