Singla Rupak, Khan Samsuddin, Silsarma Arunima, Chavan Vijay, Mahajan Raman, Mansoor Homa, Devan Ravindra Kumar, Singla Neeta, Bhalla Manpreet, Kumar Gavish, Singh Pramila, Iyer Aparna, Morales Mabel, Devkota Satish Chandra, Dalal Alpa, Spencer Hannah, Isaakidis Petros
National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India.
Médecins Sans Frontières, Mumbai, India.
Clin Infect Dis. 2025 Mar 13. doi: 10.1093/cid/ciaf068.
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.
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.
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.
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.
贝达喹啉（BDQ）耐药性是抗击结核病（TB），尤其是耐多药（MDR）菌株过程中的一项严峻挑战。BDQ作为治疗耐多药结核病的关键药物，其耐药性的出现对结核病治疗效果构成了重大威胁。
德里的国家结核病和呼吸系统疾病研究所及孟买的无国界医生诊所为疑似或确诊治疗失败的患者提供基于BDQ、地拉马尼和碳青霉烯的治疗方案。对所有接触过BDQ的患者进行BDQ表型药物敏感性测试（DST）。根据接触史、合并症、药物相互作用、既往药物不良反应和DST结果制定个体化治疗方案。
在2020年12月至2022年12月期间接触过BDQ的117例患者中，42例（36%）出现了BDQ耐药菌株。中位（IQR）年龄为24（22 - 32）岁，女性63例（54%），94%为肺结核患者。BDQ耐药菌株患者年龄更大（中位年龄：27岁对23岁；P = 0.04），更易出现肺空洞（风险比[RR]：1.8；95%置信区间：1.1 - 3.1；P = 0.02），且对氯法齐明耐药（RR：2.3；95%置信区间：1.5 - 3.6；P = 0.001）。总体而言，102例患者开始治疗。与BDQ敏感患者相比，BDQ耐药患者出现不良结局的风险更高（RR：2.1；95%置信区间：1.5 - 2.8；P < 0.001）。总体而言，87%（33/38）的BDQ耐药患者治疗结局不佳：15例（40%）死亡，15例（40%）治疗失败，3例（8%）失访。
该研究凸显了既往治疗患者中令人担忧的BDQ耐药率，导致治疗结局不佳。为防止治疗失败，我们建议实施BDQ-DST，开发经济实惠且准确的BDQ耐药快速检测方法，并加大新型结核病药物的研发力度。
