Islam Md Mahmudul, Alam Md Shah, Liu Zhiyong, Khatun Mst Sumaia, Yusuf Buhari, Hameed H M Adnan, Tian Xirong, Chhotaray Chiranjibi, Basnet Rajesh, Abraha Haftay, Zhang Xiaofan, Khan Shahzad Akbar, Fang Cuiting, Li Chunyu, Hasan Sohel, Tan Shouyong, Zhong Nanshan, Hu Jinxing, Zhang Tianyu
State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Front Med (Lausanne). 2024 Jan 10;10:1304857. doi: 10.3389/fmed.2023.1304857. eCollection 2023.
Clofazimine (CFZ) and bedaquiline (BDQ) are currently used for the treatment of multidrug-resistant (MDR) () strains. In recent years, adding CFZ and BDQ to tuberculosis (TB) drug regimens against MDR strains has significantly improved treatment results, but these improvements are threatened by the emergence of MDR and extensively drug-resistant (XDR) strains. Recently, CFZ and BDQ have attracted much attention for their strong clinical efficacy, although very little is known about the mechanisms of action, drug susceptibility test (DST), resistance mechanisms, cross-resistance, and pharmacokinetics of these two drugs. In this current review, we provide recent updates on the mechanisms of action, DST, associated mutations with individual resistance and cross-resistance, clinical efficacy, and pharmacokinetics of CFZ and BDQ against strains. Presently, known mechanisms of resistance for CFZ and/or BDQ include mutations within the , , , and genes. The cross-resistance between CFZ and BDQ may reduce available MDR-/XDR-TB treatment options. The use of CFZ and BDQ for treatment in the setting of limited DST could allow further spread of drug resistance. The DST and resistance knowledge are urgently needed where CFZ and BDQ resistance do emerge. Therefore, an in-depth understanding of clinical efficacy, DST, cross-resistance, and pharmacokinetics for CFZ and BDQ against can provide new ideas for improving treatment outcomes, reducing mortality, preventing drug resistance, and TB transmission. Along with this, it will also help to develop rapid molecular diagnostic tools as well as novel therapeutic drugs for TB.
氯法齐明（CFZ）和贝达喹啉（BDQ）目前用于治疗耐多药（MDR）结核分枝杆菌菌株。近年来，在针对MDR结核分枝杆菌菌株的结核病（TB）药物治疗方案中添加CFZ和BDQ已显著改善了治疗效果，但这些改善受到MDR和广泛耐药（XDR）结核分枝杆菌菌株出现的威胁。最近，CFZ和BDQ因其强大的临床疗效而备受关注，尽管对这两种药物的作用机制、药敏试验（DST）、耐药机制、交叉耐药性和药代动力学知之甚少。在本综述中，我们提供了关于CFZ和BDQ针对结核分枝杆菌菌株的作用机制、DST、与个体耐药和交叉耐药相关的突变、临床疗效和药代动力学的最新进展。目前，已知的CFZ和/或BDQ耐药机制包括rpoB、katG、inhA和embB基因内的突变。CFZ和BDQ之间的交叉耐药性可能会减少可用的MDR/XDR-TB治疗选择。在DST有限的情况下使用CFZ和BDQ进行治疗可能会使耐药性进一步传播。在确实出现CFZ和BDQ耐药的地方，迫切需要DST和耐药知识。因此，深入了解CFZ和BDQ针对结核分枝杆菌的临床疗效、DST、交叉耐药性和药代动力学可为改善治疗结果、降低死亡率、预防耐药性和结核病传播提供新思路。与此同时，这也将有助于开发用于结核病的快速分子诊断工具以及新型治疗药物。
