Globally increasing antibiotic resistance (AR) will only be reversed through a suite of multidisciplinary actions (One Health), including more prudent antibiotic use and improved sanitation on international scales. Relative to sanitation, advanced technologies exist that reduce AR in waste releases, but such technologies are expensive, and a strategic approach is needed to prioritize more affordable mitigation options, especially for Low- and Middle-Income Countries (LMICs). Such an approach is proposed here, which overlays the incremental cost of different sanitation options and their relative benefit in reducing AR, ultimately suggesting the “next-most-economic” options for different locations. When considering AR gene fate versus intervention costs, reducing open defecation (OD) and increasing decentralized secondary wastewater treatment, with condominial sewers, will probably have the greatest impact on reducing AR, for the least expense. However, the best option for a given country depends on the existing sewerage infrastructure. Using Southeast Asia as a case study and World Bank/WHO/UNICEF data, the approach suggests that Cambodia and East Timor should target reducing OD as a national priority. In contrast, increasing decentralized secondary treatment is well suited to Thailand, Vietnam and rural Malaysia. Our approach provides a science-informed starting point for decision-makers, for prioritising AR mitigation interventions; an approach that will evolve and refine as more data become available.
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