Bedaquiline Fumarate: A Comprehensive Monograph on a Cornerstone of Multidrug-Resistant Tuberculosis Therapy

Executive Summary

Bedaquiline represents a landmark achievement in the field of infectious diseases, emerging as the first novel anti-tuberculosis agent with a unique mechanism of action to be approved in over four decades. Its development and introduction have fundamentally altered the therapeutic landscape for patients afflicted with multidrug-resistant tuberculosis (MDR-TB), a growing global health crisis characterized by poor treatment outcomes and high mortality. This monograph provides a comprehensive analysis of Bedaquiline Fumarate, marketed as Sirturo®, from its molecular pharmacology to its global regulatory and public health impact.

The drug's novelty lies in its classification as a diarylquinoline antimycobacterial, which exerts its potent bactericidal and sterilizing effects by specifically inhibiting the proton pump of adenosine 5'-triphosphate (ATP) synthase in Mycobacterium tuberculosis. This blockade of the bacterium's primary energy-generating pathway is effective against both actively replicating and dormant bacilli, a key factor in its clinical efficacy and its potential to shorten treatment durations.

Clinical evidence, beginning with pivotal Phase II trials and culminating in the confirmatory Phase III STREAM study, has unequivocally established Bedaquiline's efficacy. When added to a background regimen, it significantly improves rates of sputum culture conversion and overall treatment success in patients with MDR-TB, pre-extensively drug-resistant (pre-XDR-TB), and extensively drug-resistant tuberculosis (XDR-TB). This body of evidence prompted the World Health Organization (WHO) to reclassify Bedaquiline as a Group A drug, recommending its inclusion in all conventional MDR-TB regimens and catalyzing a global shift towards all-oral, injection-free therapy.