The missing thread of One Health efforts: improper drug disposal as an overlooked driver of antimicrobial resistance.

With gradual recognition of the components and the stakeholders, "One Health approach" became a global strategy for mitigating antimicrobial resistance (AMR). However, the role of improper pharmaceutical disposal, particularly antimicrobials at the household level, remains largely overlooked within One Health strategies. Expired and unused medicines are frequently discarded into household waste, drains, or open environments. The bioactive pharmaceutical residues enter soil, surface water, groundwater, and sediments. Conventional waste management and wastewater treatment systems are not designed to remove these compounds, resulting in chronic, low-level environmental exposure. Such sub-inhibitory concentrations of antimicrobials exert sustained selective pressure on environmental microbial communities, which promotes the emergence, persistence, and dissemination of resistant bacteria. Discarded antimicrobials persist in aquatic and terrestrial ecosystems, reshape microbial communities, disrupt nutrient cycling, and accelerate horizontal gene transfer. The environmental resistome, a vast genetic reservoir connecting environmental microbes with human and animal pathogens, plays a key role in resistance amplification. Evidence from India and other low and middle-income countries reveals the widespread presence of "clinically important resistance genes," including extended-spectrum β-lactamases and carbapenemases, in non-clinical environments. Residues and resistant bacteria can bioaccumulate in aquatic organisms and livestock, facilitating transmission through food chains and communities and often beyond routine surveillance. Despite its significance, household pharmaceutical waste management is largely absent from national and global AMR action plans. Incorporating safe drug disposal may serve as the missing thread in the One Health, apart from environmental monitoring and ecopharmacovigilance, which are critical to reduce environmental selection pressure and resistance propagation.