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

Annals of Intensive Care - Tập 10 Số 1 - 2020
Jörn Grensemann1, David Busse2, Christina König1, Kevin Roedl1, Walter Jäger3, Dominik Jarczak1, Stefanie Iwersen‐Bergmann4, Carolin Manthey5, Stefan Kluge1, Charlotte Kloft2, Valentin Fuhrmann6
1Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
2Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Kelchstraße 31, 12169, Berlin, Germany
3Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria
4Department of Legal Medicine, University Medical Center Hamburg–Eppendorf, Butenfeld 34, 22529, Hamburg, Germany
5First Department of Internal Medicine and Gastroenterology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
6Department of Medicine B, Münster University Hospital, Albert-Schweitzer-Campus 1, 48149, Münster, Germany

Tóm tắt

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.

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Annals of Intensive Care

Tập 10 Số 1

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