Acute-on-chronic liver failure alters linezolid pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study

Background In acute-on-chronic liver failure (ACLF), adequate antibiotic dosing is challenging due to changes of drug distribution and elimination. We studied the pharmacokinetics of linezolid in critically ill patients with ACLF during continuous renal replacement therapy compared to patients witho...

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Bibliographic Details
Published in:Annals of intensive care 2023-09, Vol.13 (1), p.83-10, Article 83
Main Authors: Tikiso, Tjokosela, Fuhrmann, Valentin, König, Christina, Jarczak, Dominik, Iwersen-Bergmann, Stefanie, Kluge, Stefan, Wicha, Sebastian G., Grensemann, Jörn
Format: Article
Language:English
Subjects:
Anesthesiology
Antibiotics
Critical Care Medicine
Drug dosages
Emergency Medicine
Hemodialysis
Intensive
Intensive care
Medicine
Medicine & Public Health
Monte-Carlo simulation
Observational studies
Pharmacokinetics
Population pharmacokinetics
Target attainment
Volume of distribution
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Summary:Background In acute-on-chronic liver failure (ACLF), adequate antibiotic dosing is challenging due to changes of drug distribution and elimination. We studied the pharmacokinetics of linezolid in critically ill patients with ACLF during continuous renal replacement therapy compared to patients without concomitant liver failure (NLF). Methods In this prospective cohort study, patients received linezolid 600 mg bid. Linezolid serum samples were analyzed by high-performance liquid chromatography. Population pharmacokinetic modelling was performed followed by Monte-Carlo simulations of 150 mg bid, 300 mg bid, 450 mg bid, 600 mg bid, and 900 mg bid to assess trough concentration target attainment of 2–7 mg/L. Results Eighteen patients were included in this study with nine suffering from ACLF. Linezolid body clearance was lower in the ACLF group with mean (standard deviation) 1.54 (0.52) L/h versus 6.26 (2.43) L/h for NLF, P 
ISSN:2110-5820
2110-5820
DOI:10.1186/s13613-023-01184-z