Bedaquiline Resistance and Treatment Outcomes Among Patients With Tuberculosis Previously Exposed to Bedaquiline in India: A Multicentric Retrospective Cohort Study

Rupak Singla; Samsuddin Khan; Arunima Silsarma; Vijay Chavan; Raman Mahajan; Homa Mansoor; Ravindra Kumar Devan; Neeta Singla; Manpreet Bhalla; Gavish Kumar; Pramila Singh; Aparna Iyer; Mabel Morales; Satish Chandra Devkota; Alpa Dalal; Hannah Spencer; Petros Isaakidis

doi:10.1093/cid/ciaf068

Bedaquiline Resistance and Treatment Outcomes Among Patients With Tuberculosis Previously Exposed to Bedaquiline in India: A Multicentric Retrospective Cohort Study

Clin Infect Dis. 2025 Mar 13:ciaf068. doi: 10.1093/cid/ciaf068. Online ahead of print.

Authors

Rupak Singla¹, Samsuddin Khan², Arunima Silsarma², Vijay Chavan², Raman Mahajan², Homa Mansoor², Ravindra Kumar Devan¹, Neeta Singla¹, Manpreet Bhalla¹, Gavish Kumar¹, Pramila Singh², Aparna Iyer², Mabel Morales², Satish Chandra Devkota², Alpa Dalal³, Hannah Spencer⁴, Petros Isaakidis^{4

5}

Affiliations

¹ National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India.
² Médecins Sans Frontières, Mumbai, India.
³ Jupiter Hospital, Mumbai, India.
⁴ Southern Africa Medical Unit, Médecins Sans Frontières, Cape Town, South Africa.
⁵ Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.

PMID: 40079698
DOI: 10.1093/cid/ciaf068

Abstract

Background: Bedaquiline (BDQ) resistance presents a critical challenge in the fight against tuberculosis (TB), particularly multidrug-resistant (MDR) strains. The emergence of resistance to BDQ, a key drug in treating MDR-TB, poses significant threats to TB treatment effectiveness.

Methods: The National Institute of Tuberculosis and Respiratory Diseases in Delhi and the Médecins Sans Frontières clinic in Mumbai provide BDQ, delamanid, and carbapenem-based regimens for patients with suspected or confirmed treatment failure. BDQ phenotypic drug-susceptibility testing (DST) was performed for all BDQ-exposed patients. Treatment regimens were individualized based on exposure history, comorbidities, drug interactions, prior adverse drug reactions, and DST results.

Results: Of 117 BDQ-exposed patients from December 2020-December 2022, 42 (36%) exhibited a BDQ-resistant strain. Median (IQR) age was 24 (22-32) years, with 63 (54%) females and 94% with pulmonary TB. Patients with a BDQ-resistant strain were older (median age: 27 vs 23 years; P = .04), more likely to have lung cavities (risk ratio [RR]: 1.8; 95%-CI: 1.1-3.1; P = .02), and be resistant to clofazimine (RR: 2.3; 95%-CI: 1.5-3.6; P = .001). Overall, 102 patients initiated treatment. Patients with BDQ-resistance had higher risk of unfavorable outcomes compared with BDQ-susceptible patients (RR:2.1; 95%-CI: 1.5-2.8; P < .001). Overall, 87% (33/38) of patients with BDQ-resistance experienced unfavorable treatment outcomes: 15 (40%) died, 15 (40%) had treatment failure, and 3 (8%) were lost-to-follow-up.

Conclusions: The study highlights a concerning rate of BDQ-resistance among previously treated patients, resulting in poor treatment outcomes. To prevent treatment failure, we recommend implementing BDQ-DST, developing affordable and accurate rapid tests for BDQ-resistance, and intensifying research and development efforts for newer TB drugs.

Keywords: India; drug resistance; drug-susceptibility testing; operational research.