Abstract
BackgroundInfection 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).MethodsIn 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).ResultsNineteen 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%.ConclusionALCF 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.
Highlights
Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF)
Gram-positive bacteria were identified in four patients in microbiological sampling, Escherichia coli and Candida spp. in one case each, and no pathogens were found in two patients
Meropenem is often used as empiric broad-spectrum antimicrobial therapy in patients with ACLF suffering from sepsis and septic shock
Summary
Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Sepsis and septic shock are frequent complications in patients with acute-on-chronic liver failure (ACLF) and associated with a high mortality [1,2,3,4,5,6,7]. Empiric broad-spectrum antibiotic therapy is indicated in these critically ill patients [8]. Acute kidney injury is the most frequent type of organ failure in ACLF [3] requiring renal replacement therapy in this patient population [9]. Due to an increased volume of distribution (V) as a result of capillary leak syndrome and a decreased elimination due to organ dysfunction, antibiotic pharmacokinetics (PK) is highly variable in critical illness. Concerning hepatic insufficiency, only PK and pharmacodynamic data from patients with stable alcoholic cirrhosis are available [11], but to date, there are no available data in patients suffering from ACLF with multiorgan failure
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
