{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:44:57Z","timestamp":1788471897796,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Bedaquiline (BDQ) resistance poses a serious threat to its long-term efficacy, particularly in high-burden settings like South Africa, where data remain scattered and largely non-synthesized. Objective: This study aimed to estimate the trends of BDQ resistance in drug resistant tuberculosis (DR-TB), characterize associated resistance mechanisms, and evaluate implications for treatment outcomes in South Africa. Eligibility criteria: We included primary studies reporting BDQ resistance, resistance mechanisms, minimum inhibitory concentrations (MICs), or treatment outcomes among patients with MDR- or XDR-TB treated with BDQ-containing regimens in South Africa. Information sources: PubMed, Web of Science, and Embase were searched for studies published between January 2016 and July 2024. Risk of bias: Study quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Synthesis of results: Random-effects meta-analysis with Freeman\u2013Tukey double-arcsine transformation was used to estimate pooled BDQ resistance prevalence. Heterogeneity, sensitivity analyses, and publication bias were assessed. Results: Twenty-eight studies were included. The pooled prevalence of BDQ resistance was 6.0% (95% CI: 4.1\u20137.9%; I2 = 62%). Treatment success averaged 63.5%, and culture conversion reached 84.1%. Resistance-associated mutations were most frequently reported in Rv0678, followed by atpE and pepQ, often associated with elevated MICs (\u22652\u20134 \u03bcg\/mL). Evidence of small-study effects was observed (Egger\u2019s test, p = 0.0012). A pooled prevalence estimate was calculated; however, evidence of small-study effects suggests that estimates should be interpreted cautiously. Limitations: Heterogeneity in study design, outcome definitions, and resistance testing methods limited comparability across studies. Conclusions: Bedaquiline remains effective for DR-TB treatment in South Africa; however, emerging resistance and its molecular drivers pose a growing threat to regimen sustainability, including BPaL. Strengthened surveillance and standardized resistance testing are urgently needed.<\/jats:p>","DOI":"10.3390\/antibiotics15040385","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:55:12Z","timestamp":1775807712000},"page":"385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bedaquiline Resistance in Drug-Resistant Tuberculosis in South Africa: A Systematic Review and Meta-Analysis of Emerging Trends"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5351-7834","authenticated-orcid":false,"given":"Kabelo Gabriel","family":"Kaapu","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Limpopo, Sovenga 0727, Limpopo, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7676-2034","authenticated-orcid":false,"given":"Vukosi Treasure","family":"Makondo","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Limpopo, Sovenga 0727, Limpopo, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7445-6620","authenticated-orcid":false,"given":"Emilyn","family":"Costa Concei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Division of Molecular Biology and Human Genetics, South African Medical Research Council Centre for Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, Western Cape, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6279-6409","authenticated-orcid":false,"given":"Ivy","family":"Rukasha","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Limpopo, Sovenga 0727, Limpopo, South Africa"},{"name":"Department of Microbiology, Polokwane Laboratory, National Health Laboratory Service, Polokwane 0699, Limpopo, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Timm, J., Bateson, A., Solanki, P., Paleckyte, A., Witney, A.A., Rofael, S.A.D., Fabiane, S., Olugbosi, M., McHugh, T.D., and Sun, E. 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