Meropenem Extraction by Ex Vivo Extracorporeal Life Support Circuits

Abstract

Background Meropenem is a broad-spectrum carbapenem-type antibiotic commonly used to treat critically ill patients infected with extended-spectrum β-lactamases (ESBL)-producing Enterobacteriaceae. As many of these patients require extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), it is important to understand how these extracorporeal life support circuits impact meropenem pharmacokinetics. Based on the physicochemical properties of meropenem, it is expected that ECMO circuits will minimally extract meropenem, while CRRT circuits will rapidly clear meropenem. The present study seeks to determine the extraction of meropenem from ex vivo ECMO and CRRT circuits and elucidate the contribution of different ECMO circuit components to extraction. Methods Standard doses of meropenem were administered to three different configurations (n=3 per configuration) of blood-primed ex vivo ECMO circuits and serial sampling was conducted over 24 hours. Similarly, standard doses of meropenem were administered to CRRT circuits (n=4) and serial sampling was conducted over 4 hours. Meropenem was administered to separate tubes primed with circuit blood to serve as controls to account for drug degradation. Meropenem concentrations were quantified, and percent recovery was calculated for each sample. Results Meropenem was cleared at a similar rate in ECMO circuits of different configurations (n=3) and controls (n=6), with mean (standard deviation) recovery at 24 hours of 15.6% (12.9) in Complete circuits, 37.9% (8.3) in Oxygenator circuits, 47.1% (8.2) in Pump circuits, and 20.6% (20.6) in controls. In CRRT circuits (n=4) meropenem was cleared rapidly compared with controls (n=6) with a mean recovery at 2 hours of 2.36% (1.44) in circuits and 93.0% (7.1) in controls. Conclusion Meropenem is rapidly cleared by hemodiafiltration during CRRT. There is minimal adsorption of meropenem to ECMO circuit components; however, meropenem undergoes significant degradation and/or plasma metabolism at physiological conditions. These ex vivo findings will advise pharmacists and physicians in appropriate dosing of meropenem.