Higher than standard dosing regimen are needed to achieve optimal antibiotic exposure in critically ill patients with augmented renal clearance receiving piperacillin-tazobactam administered by continuous infusion

Purpose: To determine whether augmented renal clearance (ARC) impacts negatively on piperacillin-tazobactam unbound concentrations in critically ill patients receiving 16 g/2 g/day administered continuously. Material and methods: Fifty nine critically ill patients without renal impairment underwent 24-h creatinine clearance (Cr-CL) measurement and therapeutic drug monitoring during the first three days of antimicrobial therapy by piperacillin-tazobactam. The main outcome was the rate of piperacillin underexposure, defined by at least one of three samples under 16 mg/L Monte Carlo simulation was performed to predict the distribution of piperacillin concentrations for various Cr-CL and minimal inhibitory concentration (MIC) values. Results: The rate of piperacillin underexposure was 19%, significantly higher in ARC patients (0 vs. 31%, p =.003). A threshold of Cr-CL >= 170 mL/min had a sensitivity and specificity of 1 (MCI: 0.79-1) and 0.69 (MCI: 0.61-0.76) to predict piperacillin underexposure. In ARC patients, a 20 g,2.5 g/24 h PTZ dosing regimen was associated with the highest probability to reach the 16 mg/L empirical target, without risk of excessive dosing. Conclusions: When targeting a theoretical MIC at the upper limit of the susceptibility range, the desirable target (100%fT(>16)) may not be achieved in patients with Cr-CL >= 170 mL/min receiving PTZ 16 g/2 g/day administered continuously. (C) 2018 Elsevier Inc. All rights reserved.