A review of tuberculosis: Focus on bedaquiline

• Published in: American journal of health-system pharmacy Vol. 70; no. 22; pp. 1984 - 1994
• Main Authors: CHAN, BONNIE, KHADEM, TINA M, BROWN, JACK
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society of Health-System Pharmacists 15.11.2013; Copyright American Society of Health-System Pharmacists, Inc. All rights reserved; American Society of Health Pharmacists; Oxford University Press
• Subjects: Antitubercular Agents - administration & dosage; Antitubercular Agents - pharmacology; Antitubercular Agents - therapeutic use; Bacterial diseases; Biological and medical sciences; Diarylquinolines - administration & dosage; Diarylquinolines - pharmacology; Diarylquinolines - therapeutic use; Distribution; Drug Approval; Drug therapy; Drug Therapy, Combination; History; Human bacterial diseases; Humans; Infectious diseases; Medical sciences; Molecular Targeted Therapy; Mycobacterium; Pharmacology; Prevalence; Tuberculosis; Tuberculosis and atypical mycobacterial infections; Tuberculosis, Multidrug-Resistant - drug therapy; Tuberculosis, Multidrug-Resistant - epidemiology; United States; United States Food and Drug Administration; United States; Infection; Tuberculosis; Bedaquiline; Bacteriosis; Mycobacterial infection; Review; Antibacterial agent; Bibliographic review
• ISSN: 1079-2082; 1535-2900
• DOI: 10.2146/ajhp130199

PURPOSEThe history and prevalence of tuberculosis and the role of bedaquiline in multidrug-resistant (MDR) tuberculosis are reviewed. SUMMARYTuberculosis 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. Bedaquilineʼs 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. CONCLUSIONThe 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.