Olivier Lheureux1, Eric Trepo2,3, Maya Hites4, Frederic Cotton5, Fleur Wolff5, Rudy Surin4, Jacques Creteur1, Jean-Louis Vincent1, Thierry Gustot2,3, Frederique Jacobs4, Fabio S Taccone1. 1. Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. 2. Department of Gastroenterology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. 3. Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium. 4. Department of Infectious Diseases, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. 5. Department of Clinical Biochemistry, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
Abstract
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.
BACKGROUND & AIMS: The pharmacokinetics of β-lactam antibiotics have not been well defined in critically illpatients with cirrhosis. METHODS: We reviewed data from critically illpatients 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.
Authors: Danny Tsai; Penelope Stewart; Rajendra Goud; Stephen Gourley; Saliya Hewagama; Sushena Krishnaswamy; Steven C Wallis; Jeffrey Lipman; Jason A Roberts Journal: Antimicrob Agents Chemother Date: 2016-11-21 Impact factor: 5.191
Authors: Cristina Sanches; Geisa C S Alves; Andras Farkas; Samuel Dutra da Silva; Whocely Victor de Castro; Farah Maria Drummond Chequer; Francisco Beraldi-Magalhães; Igor Rafael Dos Santos Magalhães; André de Oliveira Baldoni; Mark D Chatfield; Jeffrey Lipman; Jason A Roberts; Suzanne L Parker Journal: Antibiotics (Basel) Date: 2022-03-24