Prevalence and outcomes of primary bedaquiline resistance in adults with rifampicin-resistant pulmonary tuberculosis

Background Bedaquiline resistance (BDQ-R) is increasing worldwide, but the contribution of primary BDQ-R remains unclear in countries with a high burden of RR-TB and widespread bedaquiline use. We aimed to estimate the prevalence of primary BDQ-R and to describe treatment outcomes amongst adults with primary BDQ-R in the Western Cape province, South Africa. Methods We conducted a retrospective cohort study of patients with BDQ-R identified through routine phenotypic bedaquiline susceptibility testing. Among patients with baseline BDQ-R (defined as resistance detected in those on no RR-TB treatment or with <1 month of treatment exposure), BDQ-R was categorised as primary (no prior bedaquiline exposure) or acquired (prior bedaquiline exposure). Drug resistance profiles, treatment outcomes, and time to culture conversion were analysed. Results Among 146 patients with baseline BDQ-R, 81 (55%) had primary BDQ-R. Resistance to other RR-TB drugs was common (except for linezolid). Of 80 patients with baseline BDQ-R and a treatment outcome, 28 (35%) died at a median of 276 days (IQR 129–459) after BDQ-R diagnosis. 117/136 (86%) achieved sputum culture conversion in a median of 97 days (IQR 89 –116). Acquired BDQ-R was associated with a lower hazard of culture conversion (adjusted HR: 0.37; p<0.001) and fewer favourable treatment outcomes (12.5% vs 47.9%; P=0.001) than primary BDQ-R. Conclusion Over half of BDQ-R cases were due to primary transmission. Outcomes were poor, but better in primary than acquired BDQ-R. Optimized susceptibility testing and treatment strategies are urgently needed to limit BDQ-R transmission.