Abstract

Antimicrobial resistance (AMR) is one of the most pressing global health threats, yet
traditional surveillance systems based on clinical isolates capture only a fraction of the
resistance circulating in human and animal populations. Wastewater- based epidemiology has
emerged as a transformative approach for tracking AMR genes at population level, offering
real-time, aggregate, and non-invasive surveillance. This comprehensive review synthesizes
evidence from 120 studies (2015- 2025) examining the role of wastewater surveillance in
monitoring antimicrobial resistance genes (ARGs). We analyze methodologies (sampling, DNA extraction, metagenomic sequencing, quantitative PCR), validation against clinical
surveillance, and applications including early warning of emerging resistance, tracking
resistance gene flow across One Health compartments (humans, animals, environment), and
evaluating community-level effects of antibiotic stewardship interventions. Evidence
demonstrates that wastewater ARG concentrations correlate with clinical resistance rates, predict outbreaks before clinical cases appear, and reveal resistance genes not yet detected in
hospitals. Wastewater surveillance successfully tracked SARS-CoV- 2 variants during the
pandemic, and parallel efforts have dramatically advanced AMR tracking. We recommend
integrating wastewater AMR surveillance into national and global surveillance networks, standardizing methodologies, establishing shared databases, and investing in low- cost
monitoring for low-resource settings. Wastewater surveillance is not a replacement for
clinical surveillance but a powerful, cost- effective complement that provides
population-level AMR intelligence.