Synergistic activities of clofazimine with moxifloxacin or capreomycin against Mycobacterium tuberculosis in China

Abstract Clofazimine (CFZ) is a promising candidate drug for use in the management of multidrug-resistant tuberculosis (MDR-TB) patients. In this study, the minimum inhibitory concentration (MIC) method and checkerboard method were used to investigate potential synergies between CFZ and moxifloxacin (MOX) or capreomycin (CAP). 30 Mycobacterium tuberculosis strains were collected, including 13 MDR strains, 2 extensive drug- resistant (XDR) strains, 3 pan-sensitive strains and 12 strains resistant to other drugs. When the minimum fractional inhibitory concentration indexes (FICIs) were calculated, synergy was found in 21 (70.00%) M. tuberculosis strains against the CFZ/CAP combination and 29 (96.67%) against the CFZ/MOX combination. When the maximum FICIs were calculated, 10 out of 15 MDR/XDR strains and 2 out of 15 other drug-resistant or pan-sensitive strains showed antagonism against the CFZ/CAP combination, whilst 8 out of 15 MDR/XDR strains and 1 out of 15 other drug-resistant or pan-sensitive strains showed antagonism against the CFZ/MOX combination, respectively. In conclusion, these findings demonstrate that the combination of CFZ and MOX shows better synergism than the combination of CFZ and CAP. The MDR/XDR isolates are more likely to show antagonism than the other drug-resistant or pan-sensitive strains in both CFZ/MOX and CFZ/CAP combinations. Taken together, we suggest that CFZ, in combination with MOX, may be a promising drug regimen for the treatment of MDR-TB, especially for the susceptible M. tuberculosis infectious.