Acute-on-chronic liver failure alters linezolid pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study
Abstract 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 patie...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-09-01
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| Series: | Annals of Intensive Care |
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| Online Access: | https://doi.org/10.1186/s13613-023-01184-z |
| _version_ | 1797451489040400384 |
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| author | Tjokosela Tikiso Valentin Fuhrmann Christina König Dominik Jarczak Stefanie Iwersen-Bergmann Stefan Kluge Sebastian G. Wicha Jörn Grensemann |
| author_facet | Tjokosela Tikiso Valentin Fuhrmann Christina König Dominik Jarczak Stefanie Iwersen-Bergmann Stefan Kluge Sebastian G. Wicha Jörn Grensemann |
| author_sort | Tjokosela Tikiso |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-09T14:55:24Z |
| format | Article |
| id | doaj.art-9101e6a64ee147c793ab3d1e070406b1 |
| institution | Directory Open Access Journal |
| issn | 2110-5820 |
| language | English |
| last_indexed | 2024-03-09T14:55:24Z |
| publishDate | 2023-09-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Annals of Intensive Care |
| spelling | doaj.art-9101e6a64ee147c793ab3d1e070406b12023-11-26T14:13:10ZengSpringerOpenAnnals of Intensive Care2110-58202023-09-0113111010.1186/s13613-023-01184-zAcute-on-chronic liver failure alters linezolid pharmacokinetics in critically ill patients with continuous hemodialysis: an observational studyTjokosela Tikiso0Valentin Fuhrmann1Christina König2Dominik Jarczak3Stefanie Iwersen-Bergmann4Stefan Kluge5Sebastian G. Wicha6Jörn Grensemann7Department of Clinical Pharmacy, Institute of Pharmacy, University of HamburgDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfDepartment of Legal Medicine, University Medical Center Hamburg-EppendorfDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfDepartment of Clinical Pharmacy, Institute of Pharmacy, University of HamburgDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfAbstract 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.https://doi.org/10.1186/s13613-023-01184-zAntibioticsTarget attainmentIntensive careVolume of distributionMonte-Carlo simulationPopulation pharmacokinetics |
| spellingShingle | Tjokosela Tikiso Valentin Fuhrmann Christina König Dominik Jarczak Stefanie Iwersen-Bergmann Stefan Kluge Sebastian G. Wicha Jörn Grensemann Acute-on-chronic liver failure alters linezolid 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 linezolid pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study |
| title_full | Acute-on-chronic liver failure alters linezolid pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study |
| title_fullStr | Acute-on-chronic liver failure alters linezolid pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study |
| title_full_unstemmed | Acute-on-chronic liver failure alters linezolid pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study |
| title_short | Acute-on-chronic liver failure alters linezolid pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study |
| title_sort | acute on chronic liver failure alters linezolid 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 | https://doi.org/10.1186/s13613-023-01184-z |
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