• Cédric Carrié, Rachel Legeron, Laurent Petit, Julien Ollivier, Vincent Cottenceau, Nicolas d'Houdain, Philippe Boyer, Mélanie Lafitte, Fabien Xuereb, François Sztark, Dominique Breilh, and Matthieu Biais.
• Anesthesiology and Critical Care Department, CHU Bordeaux, 33000 Bordeaux, France. Electronic address: cedric.carrie@chu-bordeaux.fr.
• J Crit Care. 2018 Dec 1; 48: 66-71.

PurposeTo 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 MethodsFifty nine critically ill patients without renal impairment underwent 24-h creatinine clearance (CrCL) 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 CrCL and minimal inhibitory concentration (MIC) values.ResultsThe rate of piperacillin underexposure was 19%, significantly higher in ARC patients (0 vs. 31%, p = .003). A threshold of CrCL ≥ 170 mL/min had a sensitivity and specificity of 1 (95%CI: 0.79-1) and 0.69 (95%CI: 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.ConclusionsWhen 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 CrCL ≥ 170 mL/min receiving PTZ 16 g/2 g/day administered continuously.Copyright © 2018 Elsevier Inc. All rights reserved.

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