抗结核药物贝达喹啉与氯法齐明耐药的研究现状

耐多药/利福平耐药结核病(multidrug-/rifampicin-resistant tuberculosis, MDR/RR-TB)和广泛耐药结核病(extensively drug-resistant tuberculosis, XDR-TB)的出现对世界范围内结核病的控制构成了巨大威胁。由于缺乏有效的药物，MDR-TB患者的治疗成功率仅为59%,XDR-TB患者的治疗成功率不足50%。近年来，新型抗结核药物贝达喹啉(bedaquiline, Bdq)、老药新用药物氯法齐明(clofazimine, Cfz)在MDR/RR-TB和XDR-TB患者中的应用可以明显改善患者的治疗结局。两种药物均通过损害分枝杆菌能量代谢来发挥作用，尽管存在交叉耐药，但在临床治疗中仍然被临床医生联合使用。因此，在临床应用过程中除了需要关注药物的不良反应外，也应关注Bdq和Cfz的耐药情况。笔者旨在总结Bdq和Cfz耐药相关机制，以及临床治疗中Bdq和Cfz耐药性的出现情况，讨论如何延缓Bdq和Cfz获得性耐药的增加和传播。

Research status of drug resistance of antituberculosis drugs bedaquiline and clofazimine

The emergence of multidrug-/rifampicin-resistant tuberculosis (MDR/RR-TB) and extensively drug-resistant tuberculosis (XDR-TB) poses a huge threat to tuberculosis (TB) control worldwide. Due to the lack of effective drugs, the success rate for MDR-TB patients was only 59%, and less than 50% for XDR-TB patients. In recent years, the application of the new anti-TB drug bedaquiline (Bdq) and the old drug clofazimine (Cfz) in patients with MDR/RR-TB and XDR-TB can significantly improve the treatment outcomes of patients. Both drugs work by impairing energy metabolism of mycobacterium and are still used in combination by clinicians in clinical care despite cross-resistance. Therefore, in the process of clinical application, attention should be paid not only to the adverse drug reactions, but also to the drug resistance of Bdq and Cfz. The author aims to summarize the mechanisms associated with drug resistance of Bdq and Cfz, the emergence of drug resistance of Bdq and Cfz in clinical treatment, and to discuss how to delay the accumulation and spread of acquired drug resistance of Bdq and Cfz.