Extracorporeal membrane oxygenation (ECMO) has emerged as a crucial modality in managing severe cardiac and respiratory failure; however, nosocomial infections and complex antimicrobial prescribing challenges may accompany its use.

This review examines the unique interplay between infection risk, ECMO-related alterations in antimicrobial pharmacokinetics/pharmacodynamics, and the important role of antimicrobial stewardship.

We performed a comprehensive literature search in PubMed, Embase, Cochrane Library, and Web of Science electronic libraries, to identify studies relevant to antimicrobial stewardship during ECMO. The search was conducted using the, from database inception to December 2025.

The ECMO circuit sequesters and redistributes antimicrobials, increasing the risk of both underdosing and toxicity. Additionally, critically ill patients frequently face clinical challenges that may complicate antibiotic therapy, such as metabolic derangements and renal replacement therapy. The use of prophylactic antibiotics remains a topic of controversy, with evidence suggesting only limited benefit in preventing infections while promoting antimicrobial resistance. In this respect, emerging studies highlight the feasibility, if not yet efficacy, of stewardship interventions such as protocol-driven prophylaxis, therapeutic drug monitoring, and timely de-escalation of broad-spectrum agents. Interprofessional antimicrobial stewardship programs may reduce antimicrobial consumption and costs without compromising patient outcomes. Non-pharmacologic infection control measures, including strict aseptic techniques and adherence to preventive bundles, are essential complements to antimicrobial strategies. Despite the growing evidence base, significant knowledge gaps persist regarding optimal dosing regimens and stewardship frameworks tailored to ECMO patients.

Critical illness and ECMO alter antimicrobial exposure and antibiotic use in such complex clinical scenarios necessitates stewardship approaches to prevent antimicrobial resistance. Interprofessional stewardship programs combining judicious antimicrobial use with robust non-pharmacologic infection prevention may reduce antimicrobial consumption and resistance without compromising outcomes, despite ongoing evidence gaps.