Extended versus Standard Bedaquiline Treatment for MDR/RR-TB: A 5-Year Multi-Center Study on Clinical Outcomes and Cardiac Safety in China

BACKGROUND: Multidrug-resistant and rifampin-resistant tuberculosis (MDR/RR-TB) remains a formidable challenge to global health. While the integration of bedaquiline (BDQ) has revolutionized the therapeutic landscape for MDR/RR-TB, the clinical necessity and safety profile of extending BDQ administration beyond the conventional 24-week regimen-especially in complex or high-risk cohorts-remain insufficiently characterized. METHODS: This multi-center retrospective cohort study analyzed 189 patients with MDR/RR-TB in China between January 2019 and January 2024. Patients were stratified into a standard-duration group (≤6 months) and an extended-duration group (>6 months). Treatment efficacy, cumulative culture conversion rates, and adverse events (AEs) were comparatively evaluated. Multivariable logistic regression was employed to identify independent predictors of severe Fridericia-corrected QT (QTcF) prolongation (>500 ms). RESULTS: No significant differences were observed in favorable treatment outcomes between the extended and standard groups (86.8% vs. 85.8%; P = 0.845). Culture conversion rates at the end of treatment were comparable (94.7% vs. 92.0%; P = 0.457). Regarding cardiac safety, the incidence of QTcF >500 ms did not differ significantly between the two cohorts (7.9% vs. 10.6%; P = 0.528). Notably, pre-existing cardiac disease was identified as the most potent independent risk factor for severe QTcF prolongation (OR: 9.01; 95% CI: 2.53-32.12; P < 0.001), rather than the duration of BDQ exposure. CONCLUSIONS: Extended BDQ treatment is both efficacious and well-tolerated in patients with MDR/RR-TB. Prolonged exposure does not inherently increase the risk of cardiotoxicity, suggesting that BDQ duration can be personalized based on clinical need, provided that baseline cardiac comorbidities are rigorously managed.