Establishing the Safety and Efficacy of Bedaquiline‐Containing Regimen for the Treatment of Drug‐Resistant Tuberculosis: A Systematic Review and Meta‐Analysis of Randomized Clinical Trials

The risks and benefits of bedaquiline (BDQ) for treatment of drug‐resistant tuberculosis (DR‐TB) have not been firmly established. We aimed to assess the safety and efficacy of BDQ‐containing regimens for the treatment of DR‐TB as evidenced in available randomized controlled trials (RCTs). In this systematic review and meta‐analysis, five databases (i.e., ClinicalTrials.gov, Cochrane CENTRAL, PubMed, ScienceDirect, and SinoMed) were searched. RCTs among DR‐TB patients that had a control arm were eligible. The safety endpoints were all‐cause mortality and serious adverse effects (SAEs). Efficacy outcomes were sputum culture conversion rate at 8–12 weeks and 24–26 weeks, treatment success, and time to culture conversion. A total of 476 records were screened; 18 met the eligibility criteria. The pooled analysis included 2520 participants (55.8% received BDQ‐containing regimens, n = 1408). Pooled safety outcomes showed no significant reduction in all‐cause mortality (relative risk [RR] [95 % confidence interval (CI)] = 0.94 [0.41–2.20]) or SAEs (RR [95 % CI] = 0.91 [0.67–1.23]) in the BDQ‐regimen group. Pooled efficacy outcomes showed significantly superior culture conversion rates at 8–12 weeks (RR [95 % CI] = 1.35 [1.10–1.65]) and 24–26 weeks (RR [95 % CI] = 1.25 [1.15–1.36]), more treatment success (RR [95 % CI] = 1.30 [1.17–1.44]), and a 17‐day reduction in the time to culture conversion (standardized mean difference [SMD] [95 % CI] = −17.46 [−34.82 to −0.11]) in the BDQ‐regimen group (reference: non‐BDQ regimen). Overall, BDQ regimens showed significant treatment effect against DR‐TB but did not reduce mortality or SAEs.