The silent pandemic of antimicrobial resistance: a one health systems approach

Antimicrobial resistance (AMR) has emerged as a critical global health challenge, threatening the effective treatment of infectious diseases across human, animal, and environmental systems and reflecting the interconnected nature of the One Health framework. Current estimates indicate that AMR caused approximately 1.27 million deaths in 2019, with projections suggesting it could lead to up to 10 million deaths annually by 2050 if left unaddressed. This review synthesizes evidence on the major molecular mechanisms driving resistance, including enzymatic inactivation of antibiotics, target site modification, efflux pump activity, and horizontal gene transfer mediated by mobile genetic elements. It further examines the growing resistance to critically important and last-resort antibiotics such as cephalosporins, fluoroquinolones, and colistin, highlighting the role of antimicrobial use in livestock, aquaculture, and clinical settings in accelerating resistance. Environmental reservoirs, including pharmaceutical effluents, wastewater systems, and agricultural runoff, are identified as key contributors to the persistence and dissemination of antimicrobial resistance genes. The review also evaluates global surveillance systems and antimicrobial stewardship programs, while emphasizing persistent gaps in low- and middle-income countries due to limited infrastructure, regulation, and awareness. Socioeconomic factors, inadequate sanitation, and unregulated antibiotic use further compound the burden of AMR, while the declining pipeline of new antimicrobials underscores the urgency for innovation. Addressing AMR requires coordinated global action through strengthened stewardship, integrated surveillance, regulatory reforms, environmental management, and investment in research, guided by a comprehensive One Health approach. Without immediate and sustained intervention, AMR is poised to undermine decades of medical progress and become a leading cause of mortality worldwide.