Titel
Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study
Autor*in
Jörn Grensemann
Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf
David Busse
Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin
Christina König
Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf
... show all
Abstract
Background: Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Adequate dosing of antimicrobial therapy is of central importance to improve outcome. Liver failure may alter antibiotic drug concentrations via changes of drug distribution and elimination. We studied the pharmacokinetics of meropenem in critically ill patients with ACLF during continuous veno-venous hemodialysis (CVVHD) and compared it to critically ill patients without concomitant liver failure (NLF).
Methods: In this prospective cohort study, patients received meropenem 1 g tid short-term infusion (SI). Meropenem serum samples were analyzed by high-performance liquid chromatography. A population pharmacokinetic analysis was performed followed by Monte Carlo simulations of (A) meropenem 1 g tid SI, (B) 2 g loading plus 1 g prolonged infusion tid (C) 2 g tid SI, and (D) 2 g loading and continuous infusion of 3 g/day on days 1 and 7. Probability of target attainment (PTA) was assessed for 4× the epidemiological cut-off values for Enterobacterales (4 × 0.25 mg/L) and Pseudomonas spp. (4 × 2 mg/L).
Results: Nineteen patients were included in this study. Of these, 8 patients suffered from ACLF. A two-compartment model with linear clearance from the central compartment described meropenem pharmacokinetics. The peripheral volume of distribution (V2) was significantly higher in ACLF compared to NLF (38.6L versus 19.7L, p = .05). PTA for Enterobacterales was achieved in 100% for all dosing regimens. PTA for Pseudomonas spp. in ACLF on day 1/7 was: A: 18%/80%, B: 94%/88%, C: 85%/98% D: 100%/100% and NLF: A: 48%/65%, B: 91%/83%, C: 91%/93%, D: 100%/100%.
Conclusion: ALCF patients receiving CVVHD had a higher V2 and may require a higher loading dose of meropenem. For Pseudomonas, high doses or continuous infusion are required to reach PTA in ACLF patients.
Stichwort
AntibioticsTarget attainmentIntensive careVolume of distributionMonte Carlo simulationPopulation pharmacokineticsProbability of target attainment
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
Erschienen in
Titel
Annals of Intensive Care
Band
10
ISSN
2110-5820
Erscheinungsdatum
2020
Publication
Springer Science and Business Media LLC
Erscheinungsdatum
2020
Zugänglichkeit
Rechte
Rechteangabe
© The Author(s) 2020
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