Mtolo, LuckyNgoma, NqobileNaidoo, Saloshini2025-11-142025-11-142025-10Mtolo, L., Ngoma, N. & Naidoo, S. Treatment outcomes of short-regimen multi-drug resistant tuberculosis in uMkhanyakude district (2018–2022) South Africa: a retrospective, cross-sectional study. BMC Infectious Diseases 25, 1376: 1-11 (2025). https://doi.org/10.1186/s12879-025-11667-y.1471-2334 (online)10.1186/s12879-025-11667-yhttp://hdl.handle.net/2263/105296BACKGROUND : Rifampicin-resistant / Multidrug-resistant tuberculosis (RR/MDR-TB), remains a major global health challenge, exacerbated by socioeconomic factors, poor treatment outcomes, and rising drug resistance. In response, RR/MDR-TB care has been decentralised to district hospitals in uMkhanyakude Health District to improve treatment access. This study aimed to assess treatment outcomes of patients receiving the nine-month short regimen for RR/MDR-TB in uMkhanyakude District from 2018 to 2022, and to identify socio-demographic and clinical factors associated with treatment success or failure. METHODS : A retrospective cross-sectional study was conducted among patients aged 18 years and older who received a nine-month short-course RR/MDR-TB treatment regimen at decentralised facilities in KwaZulu-Natal’s uMkhanyakude District from 2018 to 2022. Data were collected through clinical chart reviews, and descriptive statistics and multivariable regression analysis were used to identify predictors of treatment outcome. RESULTS : Among 375 RR/MDR-TB patients on nine-month short-course therapy, 50.1% (n = 188) were Males. Most patients 39.5%, (n = 148) were aged 35–51 years. The treatment success rate was 81.3% (n = 305), with 48.8% (n = 183) cured and 32.5% (n = 122) completing treatment without a confirmed bacteriological cure. Unsuccessful treatment outcomes occurred in 18.7% (n = 70) of patients, including deaths 3.2% (n = 12), treatment failures 3.7% (n = 14), loss to follow-up was 6.7% (n = 25) and treatment interruption leading to unsuccessful outcomes in 5.1% (n = 19). Occupational status, treatment interruption, and adverse drug reactions (ADRs) were significant predictors of treatment failure. Employed patients had higher odds of failure (aOR = 10.5, p = 0.001). Shorter treatment interruption (1 month) was protective (OR = 0.02, p = 0.001). ADRs increased the risk of failure (OR = 4.2, p = 0.001). CONCLUSION : The treatment success rate for patients on the RR/MDR-TB nine-month short-course in uMkhanyakude District was high. Being employed was identified as a significant predictor of treatment failure, emphasising the need for targeted interventions for employed individuals. Further research is needed to explore Directly Observed Treatment (DOT) options for employed patients.en© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Rifampicin-resistant/Multidrug-resistant tuberculosis (RR/MDR-TB)Tuberculosis (TB)Multidrug-resistant tuberculosis (MDR-TB)Treatment outcomesNine-month short-regimen therapyUMkhanyakude districtSouth Africa (SA)Article