• Olivier Lheureux, Eric Trepo, Maya Hites, Frederic Cotton, Fleur Wolff, Rudy Surin, Jacques Creteur, Jean-Louis Vincent, Thierry Gustot, Frederique Jacobs, and Fabio S Taccone.
• Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
• Liver Int. 2016 Jul 1; 36 (7): 1002-10.

Background & AimsThe pharmacokinetics of β-lactam antibiotics have not been well defined in critically ill patients with cirrhosis.MethodsWe reviewed data from critically ill patients with cirrhosis and matched controls in whom routine therapeutic drug monitoring of two broad-spectrum β-lactam antibiotics (piperacillin/tazobactam and meropenem) had been performed. Serum drug concentrations were measured twice by high-performance liquid chromatography. Antibiotic pharmacokinetics were calculated using a one-compartment model. We considered that therapy was adequate when serum drug concentrations were between 4 and 8 times the minimal inhibitory concentration of Pseudomonas aeruginosa during optimal periods of time for each drug (≥ 50% for piperacillin/tazobactam; ≥ 40% for meropenem).ResultsWe studied 38 patients with cirrhosis (16 for piperacillin/tazobactam and 22 for meropenem) and 38 matched controls. Drug dosing was similar in the two groups. The pharmacokinetics analysis showed a lower volume of distribution of meropenem (P = 0.05) and a lower antibiotic clearance of piperacillin/tazobactam (P = 0.009) in patients with cirrhosis than in the matched controls. Patients with cirrhosis were more likely than those without cirrhosis to have excessive serum β-lactam concentrations (P = 0.015), in particular for piperacillin/tazobactam.ConclusionsStandard β-lactam antibiotics regimens resulted in excessive serum concentrations in two thirds of the patients with cirrhosis. This was particularly true for piperacillin/tazobactam, probably because of reduced drug clearance.© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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