Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study
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 studie...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-04-01
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| Series: | Annals of Intensive Care |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13613-020-00666-8 |
| _version_ | 1818415283581222912 |
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| author | Jörn Grensemann David Busse Christina König Kevin Roedl Walter Jäger Dominik Jarczak Stefanie Iwersen-Bergmann Carolin Manthey Stefan Kluge Charlotte Kloft Valentin Fuhrmann |
| author_facet | Jörn Grensemann David Busse Christina König Kevin Roedl Walter Jäger Dominik Jarczak Stefanie Iwersen-Bergmann Carolin Manthey Stefan Kluge Charlotte Kloft Valentin Fuhrmann |
| author_sort | Jörn Grensemann |
| collection | DOAJ |
| description | 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 (V 2) 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 V 2 and may require a higher loading dose of meropenem. For Pseudomonas, high doses or continuous infusion are required to reach PTA in ACLF patients. |
| first_indexed | 2024-12-14T11:32:32Z |
| format | Article |
| id | doaj.art-5d191904286d467089c35c2382ffdba5 |
| institution | Directory Open Access Journal |
| issn | 2110-5820 |
| language | English |
| last_indexed | 2024-12-14T11:32:32Z |
| publishDate | 2020-04-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Annals of Intensive Care |
| spelling | doaj.art-5d191904286d467089c35c2382ffdba52022-12-21T23:03:14ZengSpringerOpenAnnals of Intensive Care2110-58202020-04-0110111010.1186/s13613-020-00666-8Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational studyJörn Grensemann0David Busse1Christina König2Kevin Roedl3Walter Jäger4Dominik Jarczak5Stefanie Iwersen-Bergmann6Carolin Manthey7Stefan Kluge8Charlotte Kloft9Valentin Fuhrmann10Department of Intensive Care Medicine, University Medical Center Hamburg-EppendorfDepartment of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet BerlinDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfDepartment of Pharmaceutical Chemistry, University of ViennaDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfDepartment of Legal Medicine, University Medical Center Hamburg-EppendorfFirst Department of Internal Medicine and Gastroenterology, University Medical Center Hamburg-EppendorfDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfDepartment of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet BerlinDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfAbstract 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 (V 2) 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 V 2 and may require a higher loading dose of meropenem. For Pseudomonas, high doses or continuous infusion are required to reach PTA in ACLF patients.http://link.springer.com/article/10.1186/s13613-020-00666-8AntibioticsTarget attainmentIntensive careVolume of distributionMonte Carlo simulationPopulation pharmacokinetics |
| spellingShingle | Jörn Grensemann David Busse Christina König Kevin Roedl Walter Jäger Dominik Jarczak Stefanie Iwersen-Bergmann Carolin Manthey Stefan Kluge Charlotte Kloft Valentin Fuhrmann Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study Annals of Intensive Care Antibiotics Target attainment Intensive care Volume of distribution Monte Carlo simulation Population pharmacokinetics |
| title | Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study |
| title_full | Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study |
| title_fullStr | Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study |
| title_full_unstemmed | Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study |
| title_short | Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study |
| title_sort | acute on chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis an observational study |
| topic | Antibiotics Target attainment Intensive care Volume of distribution Monte Carlo simulation Population pharmacokinetics |
| url | http://link.springer.com/article/10.1186/s13613-020-00666-8 |
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