Reframing “One Health” for Healthcare-Associated AMR: Target Microbes, Internal Environments, and Operational Action

While the One Health paradigm has successfully elevated antimicrobial resistance (AMR) on the global political agenda, its operationalization raises questions about how research, surveillance and interventions can best address transmission in healthcare settings. In this perspective, we argue for greater emphasis on four priorities in the application of One Health to healthcare-associated AMR. First, within the environmental dimension of One Health, internal hospital physical infrastructure, including wastewater plumbing, sink traps, and hospital drainage biofilms, warrants explicit attention because it can support the persistence, selection and transmission of resistant organisms. Second, as Article 17 of the recast Urban Wastewater Treatment Directive (Directive (EU) 2024/3019) establishes requirements for AMR monitoring in wastewater treatment plants serving agglomerations of 100,000 population equivalents and above, surveillance frameworks must match their analytical resolution to the intended public health objective. To bridge the current “actionability gap,” monitoring should combine population-level indicators with targeted genomic investigation of specialized epidemic clones and high-consequence mobile genetic elements where this detail can inform investigation or intervention. Third, global AMR strategies must balance targeted containment in clinical niches with guaranteed equitable access to essential, life-saving antimicrobials, particularly in low- and middle-income countries (LMICs) where inadequate access to effective treatment remains a major concern. Fourth, funding and evaluation criteria should judge One Health research by the importance of the question, the strength of the design and its relevance to prevention, rather than by the number of sectors represented, so that focused clinical and infrastructure studies are recognized as contributions to the wider agenda. Aligning regulatory mandates, funding mechanisms, and environmental surveillance with clinical and clonal realities is essential to strengthen the contribution of One Health to effective prevention and patient care.