In Vitro Activity of Clofazimine against Nontuberculous Mycobacteria Isolated in Beijing, China

Due to the natural resistance of nontuberculous mycobacteria (NTM) to many antibiotics, the treatment of diseases caused by NTM is often long-term but unsuccessful. The main goal of this study was to evaluate thein vitro susceptibilities to clofazimine of 209 isolates consisting of different NTM species isolated in Beijing, China. Furthermore, 47 reference strains were also tested, including 30 rapidly growing mycobacterium (RGM) species and 17 slowly growing mycobacterium (SGM) species. The potential molecular mechanism contributing to clofazimine resistance of NTM was investigated as well. Clofazimine exhibited excellent activity against both reference strains and clinical isolates of different SGM species, and most of the strains had MICs far below 1 μg/ml. Although the majority of the clinical isolates ofMycobacterium abscessus andMycobacterium fortuitum had MICs higher than 2 μg/ml, 17 out of the 30 reference strains of different RGM species had MICs below 1 μg/mlin vitro . According to the MIC distributions, the tentative epidemiological cutoff (ECOFF) values forMycobacterium kansasii ,Mycobacterium avium , andMycobacterium intracellulare were defined at 0.5 μg/ml, 1 μg/ml, and 2 μg/ml, respectively. Intriguingly, single-direction cross-resistance between bedaquiline- and clofazimine (Cfz)-resistant isolates was observed among the tested NTM species. This study demonstrates that clofazimine had strong activity against most SGM speciesin vitro , as well as some RGM species. The data provide important insights into the possible clinical application of Cfz to treat NTM infections.