Background:

Bedaquiline (TMC207) is a diarylquinoline drug and inhibits Mycobacterium tuberculosis (Mtb) F1FO-ATP synthase through targeting of both the c- and the ε-subunit[1]. Bedaquiline has uncoupler activity. Bedaquiline is used for the treatment of multi-drug resistant tuberculosis[2].

Bedaquiline inhibits the growth of TDR M. tuberculosis strains, with MIC values ranging from 0.125 to 0.5 mg/L[2]. Among slowly growing mycobacteria (SGM), bedaquiline exhibits the highest activity against Mycobacterium avium with MIC50 and MIC90 values of 0.03 and 16 mg/L, respectively. Among rapidly growing mycobacteria (RGM), Mycobacterium abscessus subsp. abscessus (M. abscessus) and Mycobacterium abscessus subsp. massiliense (M. massiliense) seem more susceptible to bedaquiline than Mycobacterium fortuitum, with MIC50 and MIC90 values of 0.13 and >16 mg/L, respectively, for both species. Bedaquiline also shows moderate in vitro activity against NTM species[3]. Bedaquiline has an excellent in vitro activity against Mycobacterium tuberculosis, including multidrug resistant M tuberculosis[4].

参考文献:
[1]. Jang JC, et al. Bedaquiline susceptibility test for totally drug-resistant tuberculosis Mycobacterium tuberculosis. J Microbiol. 2017 Apr 20.
[2]. Sarathy JP, et al. TBAJ-876 displays Bedaquiline-like mycobactericidal potency without retaining the parental drug's uncoupler activity. Antimicrob Agents Chemother. 2019 Nov 11.
[3]. Chahine EB, et al. Bedaquiline: a novel diarylquinoline for multidrug-resistant tuberculosis. Ann Pharmacother. 2014 Jan;48(1):107-15.
[4]. Pang Y, et al. In Vitro Activity of Bedaquiline against Nontuberculous Mycobacteria in China. Antimicrob Agents Chemother. 2017 Apr 24;61(5).