A Review of Tuberculosis: Focus on Bedaquiline

Document Type


Publication Date



PURPOSE: The history and prevalence of tuberculosis and the role of bedaquiline in multidrug-resistant (MDR) tuberculosis are reviewed.

SUMMARY: Tuberculosis continues to cause significant morbidity and mortality worldwide. Increasing rates of drug-resistant tuberculosis are a significant concern and pose serious implications for current and future treatment of the disease. In December 2012, the Food and Drug Administration approved bedaquiline as part of the treatment regimen for pulmonary MDR tuberculosis. Bedaquiline's unique mechanism of action presents an alternative approach to current antimycobacterial killing. By directly inhibiting adenosine triphosphate (ATP) synthase, bedaquiline is effective against both replicating and dormant mycobacteria. Pulmonary cavitary lesions can contain heterogeneous populations. This potential mix of semireplicating and hypometabolic mycobacteria is more difficult to eliminate with conventional antitubercular drugs, thus increasing the risk of resistance. No in vitro cross-resistance between bedaquiline and currently available antitubercular agents has been observed thus far. Because bedaquiline targets a completely different enzyme, cross-resistance with other conventional agents remains unlikely. Enhanced sterilizing capacity via synergistic depletion of ATP further exhibits the promising potential of bedaquiline with pyrazinamide. A course of bedaquiline requires 24 weeks of therapy in combination with other antitubercular drugs.

CONCLUSION: The approval of bedaquiline represents a major milestone in MDR tuberculosis therapy. Bedaquiline should be considered in patients who have not responded to a regimen containing four second-line drugs and pyrazinamide and patients with documented evidence of MDR tuberculosis resistant to fluoroquinolones. The exact role of bedaquiline cannot be determined until further efficacy and safety data are obtained through ongoing Phase III trials.

Publication Title

American Journal of Health-System Pharmacy





First Page


Last Page


PubMed ID



This article was published in American Journal of Health-System Pharmacy, Volume 70, Number 22, November 15, 2013, Pages 1984-94.

The published version is available at http://dx.doi.org/10.2146/ajhp130199

Copyright © 2014 by the American Society of Health-System Pharmacists

This document is currently not available here.