Population pharmacokinetics of meropenem in plasma and subcutis from patients on extracorporeal membrane oxygenation treatment

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The objectives of this study were to describe meropenem pharmacokinetics (PK) in plasma and/or subcutaneous adipose tissue (SCT) in critically ill patients receiving 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 hours. 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 forPseudomonas aeruginosa(8 mg/L) was predicted for each patient. The following targets were evaluated: 40%fT>MIC, 100%fT>MIC and 100%fT>4xMIC. For all dosing regimens simulated in both plasma and SCT 40%fT>MIC was attained. However, prolonged meropenem infusion would be needed for 100%fT>MIC and 100%fT>4xMIC to be obtained. Meropenem plasma and SCT concentrations were associated with estimated creatinine-clearance (eCLCr). Simulations showed that in patients with increased eCLCr, dose increment or continuous infusion may be needed to obtain therapeutic meropenem concentrations. In conclusion, our results show that when using traditional targets of 40%fT>MIC standard meropenem dosing of 1 g intravenously 8-hourly is likely to provide sufficient meropenem concentration to treat the problematic pathogenP. aeruginosafor patients receiving ECMO treatment. However, for patients with an increased eCLCror if more aggressive targets like 100%fT>MIC or 100%fT>4xMIC are adopted, dose increment or continuous infusion may be needed.

OriginalsprogEngelsk
Artikelnummere02390-17
TidsskriftAntimicrobial Agents and Chemotherapy
Vol/bind62
Nummer5
Antal sider13
ISSN0066-4804
DOI
StatusUdgivet - maj 2018

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