by Tjokosela
Tikiso, Valentin Fuhrmann, Christina König, Dominik Jarczak, Stefanie
Iwersen-Bergmann, Stefan Kluge, Sebastian G. Wicha and Jörn Grensemann
Annals of
Intensive Care volume 13,
Article number: 83 (2023)
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 < 0.001. A trough concentration of 2–7 mg/L was reached with the
standard dose of 600 mg bid in the NLF group in 47%, with 42% being
underexposed and 11% overexposed versus 20% in the ACLF group with 77%
overexposed and 3% underexposed. The highest probability of target exposure was
attained with 600 mg bid in the NLF group and 150 mg bid in the ACLF
group with 53%.
Conclusion
Linezolid body clearance in ACLF was markedly lower than in
NLF. Given the overall high variability, therapeutic drug monitoring (TDM) with
dose adjustments seems required to optimize target attainment. Until TDM
results are available, a dose reduction may be considered in ACLF patients to
prevent overexposure.
