Bedaquiline and delamanid treatment outcomes among patients with drug-resistant tuberculosis: a systematic review and meta-analysis

INTRODUCTION: Drug-resistant tuberculosis (DR-TB) remains a leading global health priority worldwide. The main problem for designing an effective regimen is the identification of active drugs. Two novel available drugs, delamanid and bedaquiline, are presently pivotal in ongoing scientific debates.EVIDENCE ACQUISITION: We selected published studies reporting data on the treatment outcomes of delamanid and bedaquiline in treating DR-TB cases in humans involving adult populations.EVIDENCE SYNTHESIS: A total of 38 studies provided outcomes for 4926 DR-TB patients across 16 countries. Sputum culture conversion rates to bedaquiline and delamanid-containing regimens were 75% and 71%. In addition, median (IQR) time to sputum culture conversion for delamanid plus bedaquiline was ~24 days. Treatment success of bedaquiline ranged from 4% to 100%, with an overall pooled proportion of 63% achieving treatment success. Overall pooled proportion of 78% achieving delamanid plus bedaquiline treatment success (95% CI: 61-92%). Cure rate, death and treatment failure for bedaquiline with a proportion of 58% (95% CI: 45-71%), 8% (95% CI: 3-15%), and 6% (95% CI: 2-12%) were reported, respectively. Median (IQR) time to sputum culture conversion for delamanid and bedaquiline was ~20.50 days and ~18 days, respectively. The most commonly reported adverse events were gastrointestinal side-effects, and QT prolongation.CONCLUSIONS: Treatment outcomes may suggest that the addition of delamanid and bedaquiline to DR-TB regimens may improve treatment outcomes, although associated with significant adverse events.