In Vitro Activity of the Sudapyridine (WX-081) against Non-Tuberculous Mycobacteria Isolated in Beijing, China

Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows an anti-tuberculosis activity but, unlike BDQ, did not prolong QT interval (QT) in animal model studies. This study evaluated the antimicrobial activity of this novel drug against non-tuberculous mycobacteria (NTM). Fifty reference strains of different mycobacterial species, and 132 NTM clinical isolates from four commonly isolated NTM species were recruited. The microplate alamarBlue assay was performed to determine the MIC of WX-081 and BDQ. Cytotoxicity assay was performed for both drugs using the THP-1 cells, and the minimum bactericidal concentrations (MBCs) of both drugs against the reference strains of five selected NTM species were also determined. All the tested reference strains had MICs lower than 0.5 mg/ mL, with the majority having MICs far below 0.1 mu g/ mL for WX-081. The epidemiological cut-offs of WX-081 ranged from 0.0156 mu g/ mL to 0.25 mu g/ mL against commonly isolated NTM, and this value was comparable with that of BDQ. The MBC/MIC ratios suggest a bacteriostatic activity for both drugs against the five selected NTM species. Cytotoxicity assays indicated that THP-1 cells had nearly 100% viability when exposed to WX-081 for 24 h below 4 mu g/ mL, 200- to 300-fold the MICs of Mycobacterium intracellulare, Mycobacterium avium, and Mycobacterium kansasii. WX-081 has a strong antimicrobial activity against different NTM species with low cytotoxicity and therefore has the potential to be used for treating NTM infections.

Automated summary

This study evaluated the antimicrobial activity of Sudapyridine against non-tuberculous mycobacteria (NTM) and found that it exhibits strong antimicrobial activity and low cytotoxicity against different NTM species.