Abstract:
Drug-resistant (DR)-tuberculosis (TB) is the major challenge confronting the global
tuberculosis (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 share cationic amphiphilic properties, which 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, F1/F0-ATPase, while 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.
