Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, PR China.
Department of Tuberculosis, Changsha Central Hospital, Changsha, PR China.
Int J Infect Dis. 2020 Nov;100:196-198. doi: 10.1016/j.ijid.2020.08.080. Epub 2020 Sep 2.
The World Health Organization recommends the use of bedaquiline (BDQ) to formulate efficacious combination regimens against multidrug-resistant tuberculosis (MDR-TB). This study reports, for the first time, a case series of MDR-TB patients treated with BDQ who experienced sputum culture reconversion due to emergence of nontuberculous mycobacteria (NTM) infections.
A multicentre case series was established, including patients who started treatment for laboratory-confirmed MDR-TB between January 1, 2018 and March 31, 2020. The study included patients with positive cultures that had no expression of tuberculosis-specific MPT64 protein. Multilocus sequence analysis was used to perform rapid species identification. Susceptibility to BDQ was detected using Thermo Fisher frozen microtiter plates by the laboratory staff at Beijing Chest Hospital.
Among the 286 patients receiving BDQ regimens included in this study, the emergence of NTM isolations was reported in nine cases (3.1%). After exposure to BDQ, seven out of these nine patients achieved culture conversion by 4 weeks. The median time for reported NTM infection was 12 weeks (range: 4-24 weeks). Of these, seven were rapidly growing mycobacteria, and two were slow growing. The most frequent NTM species was M. abscessus (five isolates), followed by M. fortuitum (two isolates), M. avium (one isolate), and M. intracellulare (one isolate). In addition, three patients showed resistance to BDQ at baseline.
In conclusion, our results demonstrated the emergence of novel NTM populations in MDR-TB patients during BDQ therapy. The notably rapid development of NTM infections underlines the need for systematic species identification during the follow-up period.
世界卫生组织建议使用贝达喹啉（BDQ）来制定有效的抗耐多药结核病（MDR-TB）联合治疗方案。本研究首次报告了一组因非结核分枝杆菌（NTM）感染而出现痰培养转换的 MDR-TB 患者的病例系列。
建立了一项多中心病例系列研究，纳入 2018 年 1 月 1 日至 2020 年 3 月 31 日期间开始治疗实验室确诊的 MDR-TB 的患者。研究包括培养阳性但无结核特异性 MPT64 蛋白表达的患者。采用多位点序列分析进行快速种属鉴定。北京胸科医院实验室工作人员使用 Thermo Fisher 冷冻微量滴定板检测对 BDQ 的药敏性。
在本研究纳入的 286 例接受 BDQ 方案治疗的患者中，有 9 例（3.1%）报告出现 NTM 分离株。在接触 BDQ 后，这 9 例患者中有 7 例在 4 周内实现了培养转换。报告的 NTM 感染中位时间为 12 周（范围：4-24 周）。其中 7 例为快速生长分枝杆菌，2 例为缓慢生长分枝杆菌。最常见的 NTM 菌种是脓肿分枝杆菌（5 株），其次是偶发分枝杆菌（2 株）、鸟分枝杆菌（1 株）和胞内分枝杆菌（1 株）。此外，3 例患者在基线时对 BDQ 显示耐药。
总之，我们的研究结果表明，在 MDR-TB 患者接受 BDQ 治疗期间出现了新的 NTM 群体。NTM 感染的明显快速发展强调了在随访期间进行系统种属鉴定的必要性。
