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

• Published in: International journal of antimicrobial agents Vol. 54; no. 5; pp. 642 - 646
• Main Authors: Li, Guilian, Xu, Zhengquan, Jiang, Yi, Liu, Haican, Zhao, Li-li, Li, Machao, Xu, Donglei, Zhao, Xiuqin, Liu, Zhiguang, Wang, Ruibai, Wan, Kanglin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2019
• Subjects: Antitubercular Agents - therapeutic use; Capreomycin; Capreomycin - therapeutic use; China; Clofazimine; Clofazimine - therapeutic use; Drug Synergism; Drug Therapy, Combination - methods; Humans; Microbial Sensitivity Tests; Moxifloxacin; Moxifloxacin - therapeutic use; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - isolation & purification; Synergistic activity; Tuberculosis, Multidrug-Resistant - drug therapy; Tuberculosis, Pulmonary - drug therapy; China; Clofazimine; Moxifloxacin; Mycobacterium tuberculosis; Synergistic activity; Capreomycin
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2019.06.002

•Clofazimine/moxifloxacin combinations showed excellent synergism against Mycobacterium tuberculosis.•Moxifloxacin showed better synergism than capreomycin when combined with clofazimine.•Multidrug-/extensively drug-resistant isolates more likely to show antagonism than drug-resistant/pan-sensitive strains.•Difference in antagonism relevant for clofazimine/moxifloxacin and clofazimine/capreomycin. 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). Thirty Mycobacterium tuberculosis strains were collected, including 13 MDR strains, 2 extensively 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 of 15 MDR/XDR strains and 2 of 15 other drug-resistant or pan-sensitive strains showed antagonism against the CFZ/CAP combination, whilst 8 of 15 MDR/XDR strains and 1 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 the CFZ/MOX and CFZ/CAP combinations. CFZ in combination with MOX may be a promising drug regimen for the treatment of MDR-TB, particularly for susceptible M. tuberculosis infections.