Bedaquiline for the treatment of multidrug-resistant tuberculosis: great promise
or disappointment?
#MMPMID26137207
Field SK
Ther Adv Chronic Dis
2015[Jul]; 6
(4
): 170-84
PMID26137207
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Acquired drug resistance by Mycobacterium tuberculosis (MTB) may result in
treatment failure and death. Bedaquiline was recently approved for the treatment
of multidrug-resistant tuberculosis (MDR-TB). This report examines the available
data on this novel drug for the treatment of MDR-TB. PubMed searches, last
updated 18 February 2015, using the terms bedaquiline, TMC 207 and R207910
identified pertinent English citations. Citation reference lists were reviewed to
identify other relevant reports. Pertinent MDR-TB treatment reports on the US
Food and Drug Administration, Centers for Disease Control and Prevention (CDC),
World Health Organization (WHO) and Cochrane websites were also evaluated.
Bedaquiline is an adenosine triphosphate (ATP) synthase inhibitor specific for
MTB and some nontuberculous mycobacteria. The early bactericidal activity (EBA)
of bedaquiline is delayed until ATP stores are depleted but subsequently it is
similar to the EBA of isoniazid and rifampin. Bedaquiline demonstrated excellent
minimum inhibitory concentrations (MICs) against both drug-sensitive and MDR-TB.
Adding it to the WHO-recommended MDR-TB regimen reduced the time for sputum
culture conversion in pulmonary MDR-TB. Rifampin, other cytochrome oxidase 3A4
inducers or inhibitors alter its metabolism. Adverse effects are common with
MDR-TB treatment regimens with or without bedaquiline. Nausea is more common with
bedaquiline and it increases the QTcF interval. It is not recommended for
children, pregnant or lactating women. More patients died in the
bedaquiline-treatment arms despite better microbiological outcomes in two recent
trials. The WHO and CDC published interim guidelines that recommend restricting
its use to patients with MDR-TB or more complex drug resistance who cannot
otherwise be treated with a minimum of three effective drugs. It should never be
added to a regimen as a single drug nor should it be added to a failing regimen
to prevent the emergence of bedaquiline-resistant strains.
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