In vitro and Intracellular Antibacterial Activity of Sudapyridine (WX-081) Against Tuberculosis

Background: Sudapyridine (WX-081) has exhibited equivalent efficacy than its counterpart parent drug bedaquiline (BDQ) but better safety profile against Mycobacterium tuberculosis (Mtb). Our study was aimed to evaluate in vitro activity of WX-081 against the clinical isolates of Mtb with different drug-resistance profiles and the intracellular bactericidal activity against the reference strain.Methods: The minimum inhibitory concentrations (MICs) of WX-081 and BDQ were tested against 114 Mtb clinical isolates. The intracellular activity of WX-081 and BDQ against the Mtb reference strain H37Rv in THP-1 cells was also evaluated in parallel.Results: The MICs for WX-081 of the enrolled isolates ranged from 0.0156 mu g/mL to 1 mu g/mL. The MIC50 and MIC90 of WX-081 were, respectively, 0.25 mu g/mL and 0.5 mu g/mL, with 95.6% of the enrolled strains having MICs <= 0.25 mu g/mL. For a given strain, the MIC value of WX-081 was generally equivalent to or 2-fold than MIC of BDQ. The intracellular bacterial killing was acquired with the tested drug concentrations that were presumed attainable during clinical usage.Conclusion: WX-081 exhibited potent efficacy against the clinical isolates in vitro. The intracellular killing effect of sudapyridine against the reference strain supports its potential efficacy in treating TB patients.

Automated summary

This study evaluated the in vitro activity of WX-081 against clinical isolates of drug-resistant Mycobacterium tuberculosis (Mtb) and its intracellular bactericidal activity against a reference strain. WX-081 showed potent efficacy against the tested isolates, with 95.6% of strains having a minimum inhibitory concentration (MIC) of ≤0.25 μg/mL. The intracellular killing effect of WX-081 supports its potential efficacy in treating TB patients.