title: Serum β-lactam concentrations in critically ill patients with cirrhosis: a matched case-control study.
abstract: The pharmacokinetics of β-lactam antibiotics have not been well defined in critically ill patients with cirrhosis.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lheureux
authors.affiliation: Department of Gastroenterology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.|Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Eric
authors.identifier: 0000-0003-0475-3934
authors.initials: E
authors.lastname: Trepo
authors.affiliation: Department of Infectious Diseases, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Maya
authors.initials: M
authors.lastname: Hites
authors.affiliation: Department of Clinical Biochemistry, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Cotton
authors.affiliation: Department of Clinical Biochemistry, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Fleur
authors.initials: F
authors.lastname: Wolff
authors.affiliation: Department of Infectious Diseases, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Rudy
authors.initials: R
authors.lastname: Surin
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Jacques
authors.initials: J
authors.lastname: Creteur
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.affiliation: Department of Gastroenterology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.|Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Gustot
authors.affiliation: Department of Infectious Diseases, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Frederique
authors.initials: F
authors.lastname: Jacobs
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Fabio S
authors.initials: FS
authors.lastname: Taccone
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001530:Belgium; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D016638:Critical Illness; D016208:Databases, Factual; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D016015:Logistic Models; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015999:Multivariate Analysis; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010878:Piperacillin / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy; D013845:Thienamycins / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D000077731:Meropenem; D010878:Piperacillin
keywords: cirrhosis; pharmacokinetics; sepsis; septic shock; β-lactams