BEDAQUILINE: A DRUG FOR THE TREATMENT OF MULTIDRUG-RESISTANT TUBERCULOSIS

Abstract

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis and usually affects the lungs. Transmission occurs person-to-person via airborne. According to the World Health Organization, tuberculosis is one of the top causes of death worldwide with an estimated 1.6 million deaths in 2021. Multidrug resistant forms of tuberculosis have become a major barrier to achieving successful control of TB, as therapy is less effective, associated with more adverse events and are more costly to treat when compared with standard first line therapy. An increasing frequency of multidrug-resistant TB (MDR-TB) continues to be a public health threat and needs for development of new anti-TB therapies. In 2012, bedaquiline receives U.S. Food and Drug Administration accelerated approval for treatment of pulmonary MDR-TB as part of combination therapy in adults when an effective treatment regimen cannot otherwise be provided. Bedaquiline is the first of a new class of anti-mycobacterial agents, Diarylquinoline, that inhibits the proton pump of mycobacterial ATP synthase, an enzyme that is essential for the generation of energy in Mycobacterium tuberculosis, and ultimately leads to bacterial death. In multiple clinical studies, bedaquiline plus background regimen superior to background regimen alone: lesser median time to sputum culture conversion and greater sputum culture conversion rate. The potential disadvantages of bedaquiline include highly lipophilic which can contribute to long terminal half-life and inhibition of the hERG potassium channel which can potentially lead to QT interval prolongation. Bedaquiline is oral-administered and the recommended dosage is 400 mg once daily for the first two weeks, followed by 200 mg three times per week for 22 weeks, use bedaquiline in combination with other anti-mycobacterial drugs