Cycles of antibiotic use and emergent antimicrobial resistance in the South African tuberculosis programme (1950-2021): A scoping review and critical reflections on stewardship.

The emergent threat of antimicrobial resistance (AMR) has resulted in debates around the use and preservation of effective antimicrobials. Concerns around AMR reflect a history of increasing dependence on antibiotics to address disease epidemics rooted in profound structural and systemic challenges. In the context of global health, this process, often referred to as pharmaceuticalisation, has commonly occurred within disease programmes, of which lessons are vital for adding nuance to conversations around antimicrobial stewardship. Tuberculosis (TB) is a notable example. A disease which accounts for one-third of AMR globally and remains the leading cause of death from a single infectious agent in many low - and middle-income countries, including South Africa. In this scoping review, we chart TB science in South Africa over 70 years of programming. We reviewed published manuscripts about the programme and critically reflected on the implications of our findings for stewardship. We identified cycles of programmatic responses to new drug availability and the emergence of drug resistance, which intersected with cycles of pharmaceuticalisation. These cycles reflect the political, economic, and social factors influencing programmatic decision-making. Our analysis offers a starting point for research exploring these cycles and drawing out implications for stewardship across the TB and AMR communities.