This study is the first systematic comparison of pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of continuous-infusion meropenem and piperacillin between ECMO-supported and non-ECMO control groups, highlighting the critical impact of renal function and mechanical ventilation on drug exposure. Results support implementing therapeutic drug monitoring (TDM) and individualized dosing strategies in critically ill patients to enhance antimicrobial efficacy and reduce resistance risks.
Literature Overview
The article 'Optimising Meropenem and Piperacillin Dosing in Patients Undergoing Extracorporeal Membrane Oxygenation Without Renal Dysfunction (MEPIMEX)', published in Antibiotics, systematically reviewed and summarized pharmacokinetic and pharmacodynamic characteristics of continuous-infusion meropenem and piperacillin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) without renal dysfunction. The study included 130 patients (18 ECMO-supported and 112 historical controls) and analyzed multiple clinical and mechanical factors affecting drug exposure, including renal function, mechanical ventilation, and ECMO support.
Background Knowledge
Critically ill patients exhibit significant pharmacokinetic variability due to physiological changes, making standard antibiotic doses challenging to achieve therapeutic concentrations. Beta-lactam antibiotics like meropenem and piperacillin require maintaining free drug concentrations above 4–8 times the minimum inhibitory concentration (MIC) throughout the dosing interval for optimal time-dependent bactericidal activity. While ECMO is commonly used for severe respiratory or circulatory failure, its impact on drug PK remains poorly defined. Physiological factors such as mechanical ventilation (MV) and augmented renal clearance (ARC) are also recognized to influence antibiotic clearance rates. This study systematically evaluated ECMO's impact on meropenem and piperacillin exposure while controlling for renal function, aiming to provide clinical evidence for dose optimization.
Research Methods and Experiments
This retrospective, single-center observational study analyzed 18 critically ill patients receiving ECMO support with continuous-infusion meropenem or piperacillin between April 2020 and July 2021, comparing them with 112 non-ECMO historical controls. All patients had normal renal function (eGFR > 60 mL/min/1.73 m²). The primary pharmacodynamic target was 100% fT>4xMIC, requiring free drug concentrations to maintain above 4×MIC for 24 hours. Drug concentrations were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS), with covariate analysis performed through univariate analysis and generalized estimating equations (GEE).
Key Conclusions and Perspectives
Research Significance and Prospects
This study provides preliminary clinical evidence for optimizing antibiotic regimens in ECMO patients, demonstrating renal function and mechanical ventilation as key determinants of drug exposure. Future prospective studies with larger cohorts are needed to validate these findings and evaluate TDM's actual impact on clinical outcomes.
Conclusion
The MEPIMEX study systematically evaluated the impact of ECMO support on beta-lactam antibiotic PK/PD characteristics in critically ill patients, identifying renal function and mechanical ventilation as critical determinants of drug exposure. Results support implementing therapeutic drug monitoring and individualized dosing strategies for ECMO patients to enhance efficacy and reduce resistance/toxicity risks. Although limited by small sample size and retrospective design, the standardized continuous infusion protocols and comprehensive covariate analysis offer valuable references for clinical practice. Future research should expand patient cohorts and assess TDM's clinical impact to advance precision antibiotic therapy.
