Antimicrobial resistance (AMR) represents a major One Health issue, driven by a myriad of potential accelerators that include emerging climate and social challenges. There is little doubt about the need for interventions at critical control points to reduce AMR, but addressing AMR within a single realm of One Health (for example, human, animal or environmental) is not sufficient to reduce it. Building on the past decade of research, this Perspective highlights comprehensive, systemic and integrative strategies that address the effects of anthropogenic activities and the complex relationship between humans and the environment as key targets for intersectoral and global action.

Over the last decade, numerous evidences have contributed to establish a link between the natural and human-impacted environments and the growing public health threat that is the antimicrobial resistance. In the environment, in particular in areas subjected to strong anthropogenic pressures, water plays a major role on the transformation and transport of contaminants including antibiotic residues, antibiotic-resistant bacteria, and antibiotic resistance genes. Therefore, the urban water cycle, comprising water abstraction, disinfection, and distribution for human consumption, and the collection, treatment, and delivery of wastewater to the environment, is a particularly interesting loop to track the fate of antibiotic resistance in the environment and to assess the risks of its transmission back to humans. In this article, the relevance of different transepts of the urban water cycle on the potential enrichment and spread of antibiotic resistance is reviewed. According to this analysis, some gaps of knowledge, research needs, and control measures are suggested. The critical rationale behind the measures suggested and the desirable involvement of some key action players is also discussed.