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 characterize antimicrobial sequestration within different ECMO circuit components and to describe 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 8 patients (4 VV, 4 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, no statistically significant reductions in systemic concentrations were observed for any antimicrobial. PK measures were generally consistent across sampling sites. In 20% of treatments, predefined PKPD efficacy targets were not achieved. 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 antimicrobial treatments likely reflects the marked PK variability of critical illness rather than ECMO-related drug loss alone. These exploratory results support the use of therapeutic drug monitoring to individualize antimicrobial therapy in ECMO-supported patients and the need to conduct further population PK studies to better characterize determinants of antimicrobial exposure and to clarify the clinical relevance of circuit-related drug sequestration.