NEW research from South Africa highlights the clinical challenges posed by bedaquiline-resistant rifampicin-resistant tuberculosis (RR-TB), revealing significantly delayed microbiological responses and poor outcomes for affected patients.
Bedaquiline, a cornerstone of treatment for RR-TB, is under threat from rising resistance. While awareness of this resistance is growing, little has been known about patient-level outcomes. Researchers conducted a retrospective cohort study at a tuberculosis referral hospital in East London, South Africa, comparing patients aged ≥13 years with confirmed phenotypic bedaquiline-resistant Mycobacterium tuberculosis to matched controls with susceptible disease. Matching criteria included baseline culture status, age, and HIV status. Primary endpoints were time to sputum culture conversion (SCC), modified WHO-defined unfavourable outcomes, and tuberculosis-free survival over 18 months. Adjusted analyses used Cox proportional hazards and logistic regression models.
Among 82 patients with bedaquiline-resistant TB, 70% were HIV-positive and 88% received bedaquiline-containing regimens. Adjunctive antibiotics included meropenem with amoxicillin-clavulanate in 39% of cases. Despite intensified therapy with agents such as clofazimine, linezolid, and terizidone, time to SCC was markedly prolonged: median 175 days (IQR: 100–254) compared to 32 days (IQR: 30–42) in matched controls. Bedaquiline resistance was independently associated with slower SCC (adjusted HR: 0.03, 95% CI: 0.0023–0.29; p=0.003). WHO-defined unfavourable outcomes were observed in 67% of patients, largely due to treatment failure (43%). At 18 months, only 52% of patients had reached tuberculosis-free survival, 23% had died, and 79% of survivors remained on treatment.
These findings underscore the urgent need for faster diagnostic tools and expanded access to novel therapeutic agents through clinical trials. Without such measures, the efficacy of bedaquiline and the broader success of RR-TB programmes are at risk.
Reference
Mdlenyani L et al. Treatment outcomes of bedaquiline-resistant tuberculosis: a retrospective and matched cohort study. Lancet Infect Dis. 2025; DOI: 10.1016/S1473-3099(25)00218-X.
