Optimising meropenem and piperacillin dosing in patients undergoing extracorporeal membrane oxygenation without renal dysfunction (MEPIMEX)

Abstract

Background/Objectives: Antibiotic pharmacokinetics (PK) and pharmacodynamics (PD) are altered during extracorporeal membrane oxygenation (ECMO). Meropenem and piperacillin are among the most commonly prescribed antibiotics for infections in this population. However, guidance on dosage adjustments in the ECMO setting remains limited. We aim to assess differences in meropenem and piperacillin concentrations achieved and identify the clinical, physiological, and mechanical factors influencing antibiotic exposure. Methods: This is a retrospective, single-centre, observational study comparing an ECMO cohort with a population control group from a prior study, without renal dysfunction. Demographic, clinical, PK/PD parameters, and ECMO-related data were analysed using univariate and generalised estimating equations. For both antimicrobials, the PK/PD target was set at 100%fT>4xMIC. Results: A total of 130 critically ill patients were included: 18 in the ECMO group and 112 in the control group. The mean age was 65 years (23), 67% were male and 26.9% were classified as obese. For meropenem, renal function and ECMO support significantly influenced drug exposure, with PK/PD targets being achieved in 67% of measurements; in contrast, piperacillin exposure exhibited greater variability, primarily driven by renal function and mechanical ventilation. Notably, PK/PD targets for piperacillin were met in only 20% of measurements. Conclusions: Our findings highlight the considerable variability in β-lactam exposures and PK/PD target attainment in critically ill patients. This study underscores the importance of therapeutic drug monitoring and individualised dosing in attempts to improve antimicrobial efficacy and patient outcomes in this challenging setting.