Strengthening Clinical Governance and Public Health Interventions to Improve Drug-Resistant Tuberculosis Outcomes in Rural South Africa

<b>Background/Objectives:</b> Drug-resistant tuberculosis (DR-TB) presents significant challenges to public health, particularly in rural South Africa, where limited infrastructure, high HIV co-infection rates, and weak clinical governance contribute to poor treatment outcomes. This study evaluates treatment trajectories and the impact of clinical governance and public health interventions on DR-TB outcomes in the rural Eastern Cape. <b>Methods</b>: A retrospective cohort study was conducted among 323 laboratory-confirmed DR-TB patients treated between 2018 and 2021. Kaplan-Meier curves and Cox proportional hazards analysis identified predictors of unfavorable outcomes. Logistic regression analysis simulated the impact of enhanced clinical governance scenarios on treatment success. <b>Results</b>: Treatment outcomes included cure (36.2%), completion (26.0%), loss to follow up (LTFU) (9.0%), death (9.3%), failure (2.2%), and transfer (9.3%). The median treatment duration was 10 months (IQR: 9-11). Survival analysis indicates the highest risk of death and LTFU occurred in the first 6-8 months of treatment. Multivariate Cox regression revealed that primary (HR = 0.39; 95% CI: 0.23-0.68; <i>p</i> = 0.0017) and secondary education (HR = 0.50; 95% CI: 0.31-0.85; <i>p</i> = 0.0103) were significantly protective. Paradoxically, patients with pre-XDR (HR = 0.13; <i>p</i> = 0.034) and XDR TB (HR = 0.16; <i>p</i> = 0.043) showed lower hazard of poor outcomes, likely due to early mortality or referral. HIV-negative status was associated with higher risk of poor outcomes (HR = 1.74; <i>p</i> = 0.010). Simulations suggested that improved clinical governance via better follow-up, TB/HIV integration, and adherence support could improve treatment success by up to 20 percentage points in high-impact scenarios. <b>Conclusions</b>: Strengthening clinical governance through targeted interventions could substantially reduce LTFU and mortality, especially in vulnerable subgroups. A coordinated, patient-centered approach is critical for improving DR-TB outcomes in rural, high-burden settings.