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

Guilian Li, Zhengquan Xu, Yi Jiang, Haican Liu, Li-Li Zhao, Machao Li, Donglei Xu, Xiuqin Zhao, Zhiguang Liu, Ruibai Wang, Kanglin Wan
Author Information
  1. Guilian Li: Tuberculosis branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: liguilian@icdc.cn.
  2. Zhengquan Xu: Tuberculosis branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: 523631750@qq.com.
  3. Yi Jiang: Tuberculosis branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: jiangyi@icdc.cn.
  4. Haican Liu: Tuberculosis branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: liuhaican@icdc.cn.
  5. Li-Li Zhao: Tuberculosis branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: zhaolili@icdc.cn.
  6. Machao Li: Tuberculosis branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: limachao@icdc.cn.
  7. Donglei Xu: Tuberculosis branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: xudonglei@icdc.cn.
  8. Xiuqin Zhao: Tuberculosis branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: zhaoxiuqin@icdc.cn.
  9. Zhiguang Liu: Tuberculosis branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: liuzhiguang@icdc.cn.
  10. Ruibai Wang: Tuberculosis branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: wangruibai@icdc.cn.
  11. Kanglin Wan: Tuberculosis branch, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: wankanglin@icdc.cn.

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). 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.

Keywords

MeSH Term

Antitubercular Agents
Capreomycin
China
Clofazimine
Drug Synergism
Drug Therapy, Combination
Humans
Microbial Sensitivity Tests
Moxifloxacin
Mycobacterium tuberculosis
Tuberculosis, Multidrug-Resistant
Tuberculosis, Pulmonary

Chemicals

Antitubercular Agents
Capreomycin
Clofazimine
Moxifloxacin

Word Cloud

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