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.