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The Journal of antimicrobial chemotherapy v.72 no.2, 2017년, pp.338 - 353   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Mechanisms of action and therapeutic efficacies of the lipophilic antimycobacterial agents clofazimine and bedaquiline

Cholo, Moloko C. (Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa ) ; Mothiba, Maborwa T. (Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa ) ; Fourie, Bernard (Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa ) ; Anderson, Ronald (Institute for Cellular and Molecular Medicine, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa ) ;
  • 초록  

    Drug-resistant (DR)-TB is the major challenge confronting the global TB control programme, necessitating treatment with second-line anti-TB drugs, often with limited therapeutic efficacy. This scenario has resulted in the inclusion of Group 5 antibiotics in various therapeutic regimens, two of which promise to impact significantly on the outcome of the therapy of DR-TB. These are the ‘re-purposed’ riminophenazine, clofazimine, and the recently approved diarylquinoline, bedaquiline. Although they differ structurally, both of these lipophilic agents possess cationic amphiphilic properties that enable them to target and inactivate essential ion transporters in the outer membrane of Mycobacterium tuberculosis. In the case of bedaquiline, the primary target is the key respiratory chain enzyme F 1 /F 0 -ATPase, whereas clofazimine is less selective, apparently inhibiting several targets, which may underpin the extremely low level of resistance to this agent. This review is focused on similarities and differences between clofazimine and bedaquiline, specifically in respect of molecular mechanisms of antimycobacterial action, targeting of quiescent and metabolically active organisms, therapeutic efficacy in the clinical setting of DR-TB, resistance mechanisms, pharmacodynamics, pharmacokinetics and adverse events.


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