Population Pharmacokinetics of Meropenem in Plasma and Subcutis from Patients on Extracorporeal Membrane Oxygenation Treatment.

The objectives of this study were to describe meropenem pharmacokinetics (PK) in plasma and/or subcutaneous adipose tissue (SCT) in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) treatment and to develop a population PK model to simulate alternative dosing regimens and modes of administration. We conducted a prospective observational study. Ten patients on ECMO treatment received meropenem (1 or 2 g) intravenously over 5 min every 8 h. Serial SCT concentrations were determined using microdialysis and compared with plasma concentrations. A population PK model of SCT and plasma data was developed using NONMEM. Time above clinical breakpoint MIC for Pseudomonas aeruginosa (8 mg/liter) was predicted for each patient. The following targets were evaluated: time for which the free (unbound) concentration is maintained above the MIC of at least 40% (40% f T>MIC), 100% f T>MIC, and 100% f T>4×MIC. For all dosing regimens simulated in both plasma and SCT, 40% f T>MIC was attained. However, prolonged meropenem infusion would be needed for 100% f T>MIC and 100% f T>4×MIC to be obtained. Meropenem plasma and SCT concentrations were associated with estimated creatinine clearance (eCL _Cr ). Simulations showed that in patients with increased eCL _Cr , dose increment or continuous infusion may be needed to obtain therapeutic meropenem concentrations. In conclusion, our results show that using traditional targets of 40% f T>MIC for standard meropenem dosing of 1 g intravenously every 8 h is likely to provide sufficient meropenem concentration to treat the problematic pathogen P. aeruginosa for patients receiving ECMO treatment. However, for patients with an increased eCL _Cr , or if more aggressive targets, like 100% f T>MIC or 100% f T>4×MIC, are adopted, incremental dosing or continuous infusion may be needed.
(Copyright © 2018 American Society for Microbiology.)