Development of Novel Dosing Strategy According to the Area under the Concentration-Time Curve for Vancomycin

Abstract

Vancomycin is the first-choice antimicrobial for the lethal methicillin-resistant Staphylococcus aureus infections. Therefore, the therapeutic performance of vancomycin must be enhanced. The narrow therapeutic range between clinical efficacy and toxicity necessitates therapeutic drug monitoring. Therapeutic targets were previously established by trough concentrations (10-20 mg/mL) but are now commonly determined with the area under the concentration-time curves (AUC, 400-600 mg･h/mL). However, there has not been a strategy for efficiently calculating individual AUC. This review focuses on studies pertaining to activating AUC-guided dosing of vancomycin in clinical settings. First, the author suggested a table for determining empirical dosing of vancomycin by population pharmacokinetic analysis, where weight-normalized dosing corresponded to the estimated glomerular filtration rate, also as in the case during continuous renal replacement therapy (CRRT). The author then demonstrated that Bayesian forecasting was effective for CRRT patients in regards to compliance with a target therapeutic range. The author also developed a web application to enable AUC-guided dosing. Finally, the author demonstrated a reduction in patients developing nephrotoxicity following an intervention against the concomitant use of vancomycin and tazobactam/piperacillin, a known risk factor for acute kidney injury.