Impact of Extracorporeal Membrane Oxygenation on Antimicrobial Exposure in Critically Ill Patients: A Prospective Observational Study

Background Antimicrobial pharmacokinetics (PK) in patients receiving extracorporeal membrane oxygenation (ECMO) remains poorly defined. Drug sequestration within the ECMO circuit has been reported; however, existing evidence is primarily based on ex vivo studies and small clinical series, resulting in conflicting findings with limited clinical applicability. This study aimed to quantify antimicrobial sequestration within different ECMO circuit components and to characterize the PK of meropenem, piperacillin/tazobactam, linezolid, and ceftaroline in critically ill patients receiving ECMO support. Methods We conducted a prospective, single-center observational study in critically ill patients receiving ECMO (veno-venous (VV) or veno-arterial (VA)) and treated with meropenem, piperacillin/tazobactam, linezolid, or ceftaroline. Serial blood samples were collected simultaneously from the patient’s arterial line and from pre- and post-membrane oxygenator sampling sites. Non-compartmental analysis was used to derive PK measures, and concentration differences across sampling sites were analyzed to estimate circuit-related drug sequestration. Antimicrobial target attainment was assessed according to established PKPD targets. Results A total of 237 samples from 11 patients (6 VV, 5 VA) were analyzed. Limited, component-specific sequestration was observed in the membrane oxygenator for meropenem (9.28% ± 21.6%, p = 0.046 ) and ceftaroline (14.6% ± 17.5%, p = 0.010) , for linezolid it was also identified (10.1% ± 12.3%, p = 0.005) , but in tubing and connectors. Piperacillin/tazobactam showed negligible retention. However, when considering the ECMO circuit as a whole, drug sequestration did not result in statistically significant reductions in systemic concentrations for any antimicrobial. PK measures were generally consistent across sampling sites. Despite optimized dosing regimens, 27.3% of patients failed to achieve predefined PKPD efficacy targets. Conclusions Antimicrobial sequestration within the ECMO circuit is detectable and drug- and component-specific. However, overall impact on systemic antimicrobial exposure appears limited. Inadequate PKPD target attainment in a subset of patients likely reflects the marked PK variability of critical illness rather than ECMO-related drug loss alone. These findings support the use of therapeutic drug monitoring to individualize antimicrobial therapy in ECMO-supported patients. Further population PK studies are needed to better characterize determinants of antimicrobial exposure and to clarify the clinical relevance of circuit-related drug sequestration.