Meropenem Pharmacokinetics and Target Attainment in Critically Ill Patients Are Not Affected by Extracorporeal Membrane Oxygenation: A Matched Cohort Analysis

Microorganisms

Matthias Gijsen¹  Isabel Spriet¹  Erwin Dreesen¹  Johan Nicolai²  Pieter Annaert²  Yves Debaveye³  Joost Wauters⁴ 

[1] Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium;Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium;Laboratory for Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium;Medical Intensive Care Unit, UZ Leuven, 3000 Leuven, Belgium;

关键词: meropenem;    intensive care;    pharmacokinetics;    population pharmacokinetics;    extracorporeal membrane oxygenation;    target attainment;   

DOI  :  10.3390/microorganisms9061310

来源: DOAJ

【 摘 要 】

Existing evidence is inconclusive whether meropenem dosing should be adjusted in patients receiving extracorporeal membrane oxygenation (ECMO). Therefore, the aim of this observational matched cohort study was to evaluate the effect of ECMO on pharmacokinetic (PK) variability and target attainment (TA) of meropenem. Patients admitted to the intensive care unit (ICU) simultaneously treated with meropenem and ECMO were eligible. Patients were matched 1:1, based on renal function and body weight, with non-ECMO ICU patients. Meropenem blood sampling was performed over one or two dosing intervals. Population PK modelling was performed using NONMEM7.5. TA was defined as free meropenem concentrations >2 or 8 mg/L (i.e., 1 or 4× minimal inhibitory concentration, respectively) throughout the whole dosing interval. In total, 25 patients were included, contributing 27 dosing intervals. The overall TA was 56% and 26% for the 2 mg/L and 8 mg/L target, respectively. Population PK modelling identified estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology equation and body weight, but not ECMO, as significant predictors. In conclusion, TA of meropenem was confirmed to be poor under standard dosing in critically ill patients but was not found to be influenced by ECMO. Future studies should focus on applying dose optimisation strategies for meropenem based on renal function, regardless of ECMO.

【 授权许可】

Unknown