Background Safety of treatment for multidrug-resistant tuberculosis (MDR/RR-TB) can be an obstacle to treatment completion. Evaluate safety of longer MDR/RR-TB regimens containing bedaquiline and/or delamanid. Methods Multicentre (16 countries), prospective, observational study reporting incidence and frequency of clinically relevant adverse events of special interest (AESIs) among patients who received MDR/RR-TB treatment containing bedaquiline and/or delamanid. The AESIs were defined a priori as important events caused by bedaquiline, delamanid, linezolid, injectables, and other commonly used drugs. Occurrence of these events was also reported by exposure to the likely causative agent. Results Among 2296 patients, the most common clinically relevant AESIs were peripheral neuropathy (26.4%), electrolyte depletion (26.0%), and hearing loss (13.2%) with an incidence per 1000 person months of treatment, 1000 person-months of treatment 21.5 (95% confidence interval [CI]: 19.8–23.2), 20.7 (95% CI: 19.1–22.4), and 9.7 (95% CI: 8.6–10.8), respectively. QT interval was prolonged in 2.7% or 1.8 (95% CI: 1.4–2.3)/1000 person-months of treatment. Patients receiving injectables (N = 925) and linezolid (N = 1826) were most likely to experience events during exposure. Hearing loss, acute renal failure, or electrolyte depletion occurred in 36.8% or 72.8 (95% CI: 66.0–80.0) times/1000 person-months of injectable drug exposure. Peripheral neuropathy, optic neuritis, and/or myelosuppression occurred in 27.8% or 22.8 (95% CI: 20.9–24.8) times/1000 patient-months of linezolid exposure. Conclusions AEs often related to linezolid and injectable drugs were more common than those frequently attributed to bedaquiline and delamanid. MDR-TB treatment monitoring and drug durations should reflect expected safety profiles of drug combinations. Clinical Trials Registration NCT02754765.

中文翻译：

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包含贝达喹啉和地拉马尼的治疗方案在结核病队列末期的安全性

背景 耐多药结核病 (MDR/RR-TB) 治疗的安全性可能成为治疗完成的障碍。评估含有贝达喹啉和/或地拉马尼的较长耐多药/RR-TB 方案的安全性。方法 多中心（16 个国家/地区）前瞻性观察性研究报告了接受含贝达喹啉和/或地拉马尼的耐多药/RR-TB 治疗患者中临床相关特殊不良事件 (AESI) 的发生率和频率。AESI 被先验定义为由贝达喹啉、地拉马尼、利奈唑胺、注射剂和其他常用药物引起的重要事件。这些事件的发生也通过接触可能的病原体来报告。结果 在 2296 名患者中，最常见的临床相关 AESI 是周围神经病变 (26.4%)、电解质耗竭 (26.0%) 和听力损失 (13. 2%，每 1000 人月治疗发生率，1000 人月治疗 21.5（95% 置信区间 [CI]：19.8–23.2）、20.7（95% CI：19.1–22.4）和 9.7（95% CI：8.6–10.8）。QT 间期延长 2.7% 或 1.8（95% CI：1.4–2.3）/1000 人月的治疗。接受注射剂 (N = 925) 和利奈唑胺 (N = 1826) 的患者最有可能在暴露期间发生事件。36.8% 或 72.8 (95% CI：66.0–80.0) 次/1000 人月的注射药物暴露发生听力损失、急性肾功能衰竭或电解质耗竭。周围神经病变、视神经炎和/或骨髓抑制发生率为 27.8% 或 22.8（95% CI：20.9–24.8）次/1000 患者-月的利奈唑胺暴露。结论 通常与利奈唑胺和注射药物相关的 AE 比通常归因于贝达喹啉和地拉马尼的 AE 更常见。耐多药结核病治疗监测和药物持续时间应反映药物组合的预期安全性。临床试验注册 NCT02754765。