Activity of Bedaquiline against Nontuberculous Mycobacteria in China.

The main goal of our study was to evaluate the bedaquiline susceptibility of six prevalent species of pathogenic nontuberculous mycobacteria (NTM) in China. In addition, we investigated the potential molecular mechanisms contributing to bedaquiline resistance in the different NTM species. Among slowly growing mycobacteria (SGM), bedaquiline exhibited the highest activity against ; the MIC and MIC values were 0.03 and 16 mg/liter, respectively. Among rapidly growing mycobacteria (RGM), subsp. (s) and subsp. () seemed more susceptible to bedaquiline than , with MIC and MIC values of 0.13 and >16 mg/liter, respectively, for both species. On the basis of bimodal distributions of bedaquiline MICs, we proposed the following epidemiological cutoff (ECOFF) values: 1.0 mg/liter for SGM and 2.0 mg/liter for RGM. Among , , , , , and isolates, 14 (29.8%), 41 (27.2%), 33 (39.3%), 44 (20.2%), 42 (25.8%), and 7 (31.8%), respectively, were resistant to bedaquiline. No significant differences in the proportions of bedaquiline resistance among these species were observed ( > 0.05). Genetic mutations were observed in 74 isolates (10.8%), with all nucleotide substitutions being synonymous. In conclusion, our data demonstrate that bedaquiline shows moderate activity against NTM species. Using the proposed ECOFF values, we could distinguish between bedaquiline-resistant and -susceptible strains with the broth dilution method. In addition, no nonsynonymous mutations in the gene that conferred bedaquiline resistance in all six NTM species were identified.