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

Journal of Critical Care
Cédric CarrieMatthieu Biais

Abstract

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. Fifty 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. The 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. When targeting a theoretical MIC at the upper limit of the susceptibility range, the desirable target (10...Continue Reading

Citations

Jan 4, 2019·Antimicrobial Agents and Chemotherapy·Julien OllivierDominique Breilh
Aug 2, 2019·Current Opinion in Critical Care·Pieter Depuydt, Jan J De Waele
Apr 17, 2020·European Journal of Hospital Pharmacy. Science and Practice·Joan Antoni Schoenenberger-ArnaizMercedes Palomar-Martinez
Jan 18, 2019·Critical Care : the Official Journal of the Critical Care Forum·Thibaud BesnardMatthieu Biais
Apr 23, 2020·Expert Review of Clinical Pharmacology·Dario CattaneoDeborah Je Marriott
Jun 23, 2020·Expert Review of Anti-infective Therapy·Petros I Rafailidis, Matthew E Falagas
Jan 20, 2021·Expert Opinion on Drug Metabolism & Toxicology·Alan AbdullaBirgit C P Koch
Sep 18, 2020·International Journal of Antimicrobial Agents·Suzanne L ParkerJason A Roberts
Jan 23, 2021·Pharmacotherapy·Andrew J FratoniJoseph L Kuti
Feb 12, 2021·Clinical Pharmacology and Therapeutics·Cornelia B Landersdorfer, Roger L Nation
Mar 9, 2021·The Annals of Pharmacotherapy·David E Nix, Brian L Erstad
Oct 4, 2020·Current Opinion in Infectious Diseases·Mohd H Abdul-AzizJason A Roberts
Jun 17, 2021·European Journal of Drug Metabolism and Pharmacokinetics·Erika Esteve-PitarchAriadna Padullés-Zamora

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