Informed use of bedaquiline for tuberculosis

Lessem, Erica; Bernardo, John; Reed, Caitlin; Wegener, Donna Hope

doi:10.1016/s0140-6736(15)60885-6

Cited by 1 publication

(2 citation statements)

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“…121 Despite the improved therapeutic efficacy of bedaquiline-containing regimens, safety issues remain a concern due to incomplete safety data based only on phase II clinical trials in the absence of phase III and IV trial data. 12,119,122,123 Of concern, the phase II studies revealed more deaths and AEs in the bedaquiline/BR-treated group than in the placebo/BR group. These safety issues led the WHO to recommend only conditional use of bedaquiline, limited to patients with pulmonary MDR-TB for whom no suitable alternatives are available.…”

Section: Introductionmentioning

confidence: 99%

“…125 Nevertheless, despite limited availability of safety data, usage of bedaquiline in MDR-TB chemotherapy through compassionate use programmes has been beneficial, resulting in the survival of many MDR-TB patients with more than 1258 patients worldwide having experienced clinical benefit as of October 2015. 123,[126][127][128][129] In addition, the US Agency for International Development has decided to make bedaquiline available free-of-charge to >100 global fund-eligible countries for a 4year period. 12,99,126 Chemical structure of bedaquiline 1b).…”

Section: Introductionmentioning

confidence: 99%

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

Cholo

Mothiba

Fourie

et al. 2016

J. Antimicrob. Chemother.

114

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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/F-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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