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Serum β‐lactam concentrations in critically ill patients with cirrhosis: a matched case–control study
Author(s) -
Lheureux Olivier,
Trepo Eric,
Hites Maya,
Cotton Frederic,
Wolff Fleur,
Surin Rudy,
Creteur Jacques,
Vincent JeanLouis,
Gustot Thierry,
Jacobs Frederique,
Taccone Fabio S.
Publication year - 2016
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13039
Subject(s) - piperacillin , meropenem , piperacillin/tazobactam , tazobactam , medicine , cirrhosis , pharmacokinetics , antibiotics , carbapenem , volume of distribution , pharmacology , gastroenterology , pseudomonas aeruginosa , microbiology and biotechnology , antibiotic resistance , biology , bacteria , genetics
Background & Aims The pharmacokinetics of β‐lactam antibiotics have not been well defined in critically ill patients with cirrhosis. Methods We 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). Results We 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. Conclusions Standard 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.