Antimicrobial resistance poses a global public health concern that threatens human, animal, and environmental health. If it is not addressed, it is estimated to cost the global economy between USD 90 trillion and USD 210 trillion, and the death burden could balloon to 10 million lives per year by 2050. This study aimed to explore policymakers experiences on barriers to implementing National Action Plans on antimicrobial resistance using a One Health approach in South Africa and Eswatini. Thirty-six policy makers were recruited using purposive and snowballing sampling in South Africa and Eswatini. Data were collected between November 2018 and January 2019 in South Africa, and February to March 2019 in Eswatini. Data was then analysed based on Creswell methods. Three themes and five subthemes emerged from our findings. The themes were resource barriers, political barriers, and regulation barriers to the implementation of National Action Plans on antimicrobial resistance in South Africa and Eswatini. South African and Eswatini governments should commit funds to their One Health sector budgets to enable the implementation of National Action Plans on antimicrobial resistance. Specialized human resources issues need to be prioritized to unlock barriers of implementation. A renewed political commitment is needed to combat antimicrobial resistance in a One Health approach, as it plays a significant role in resource mobilization from regional and international organizations to support the resource-constrained countries to successfully implement policies.

Background: Antimicrobial resistance (AMR) is a global threat that affects humans, animals, plants, the environment, societies, and economies—requiring urgent coordinated action. In May 2015, the World Health Assembly (WHA) adopted the Global Action Plan (GAP) on AMR, urging member states to develop and implement their own National Action Plans (NAPs) using a One Health approach. Objective: Both South Africa and Eswatini have developed NAPs and are currently in the implementation phase. However, no study has explored policymakers’ perceptions regarding NAP implementation particularly concerning coordination, accountability, resourcing, regulation and ownership. Methods: This qualitative study employed a narrative approach to explore these perceptions in South Africa and Eswatini. A total of 36 key informants were recruited using purposive and snowball sampling methods. Data was collected between November 2018 and March 2019 and transcribed verbatim. Results: Findings revealed that while governance structures for implementing NAPs exist in South Africa and Eswatini, several critical areas require urgent attention. These include limited accountability across One Health sectors, the absence of dedicated national budgets for NAP implementation, poor intra- and inter- ministerial coordination, weak medicine regulation and enforcement, and delayed multisectoral ownership of the NAPs. Conclusions: To address AMR effectively, both countries must allocate dedicated budgets, improve multisectoral integration, and strengthen regulatory frameworks regarding antimicrobial access and use across all One Health sectors. A firm commitment from all sectors is required—not just formal endorsement of the NAPs—to ensure sustainable implementation and ownership.