ABSTRACT

Antimicrobial resistance (AMR) is a quintessential One Health challenge, where the health of people, animals, and ecosystems is inextricably linked and interdependent. This review evaluates the emergence and dissemination of multidrug-resistant (MDR) pathogens by mapping the dynamic transmission cycles that bridge the human-animal-environment interface. Rather than existing in sectoral silos, resistance determinants move fluidly through the global food chain, shared water systems, and the environmental resistome, driven by systemic selection pressures. We analyse how anthropogenic inputs, such as the discharge of unmetabolized drugs from intensive livestock production and pharmaceutical manufacturing, contaminate aquatic and terrestrial ecosystems, creating “evolutionary incubators” for novel resistance mechanisms. These mechanisms are rapidly disseminated via horizontal gene transfer (HGT) on mobile genetic elements, enabling the crossing of taxonomic boundaries and the eventual spillover into human populations through contaminated produce, recreational waters, and direct zoonotic contact.
The epidemiology of this crisis reveals an alarming narrowing of therapeutic options, with surveillance data from India (2017–2024) showing a steady decline in the efficacy of last-resort agents like carbapenems and colistin across all sectors. To interrupt these cycles, we advocate for integrated antimicrobial stewardship (AMS) that addresses the entire antimicrobial lifecycle, from production and community access to safe disposal. Successful national interventions, including restrictions on over-the-counter sales under India’s Schedule H1 and the prohibition of colistin as a growth promoter, illustrate the necessity of unified policy frameworks. By leveraging advanced diagnostics, AI-driven predictive modelling, and intersectoral surveillance, this review provides a practice-oriented roadmap to preserve the global antimicrobial commons and safeguard health resilience for future generations.