Editorial Bedaquiline: An Effective Anti-tuberculous Drug with Novel Mechanism of Action Zaw Lin, Urban John Arnold D’Souza, Sadia Choudhury Shimmi Faculty of Medicine & Health Sciences, Universiti Malaysia Sabah, 88400, Kota Kinabalu, Sabah, Malaysia There were 480,000 new cases of multidrug- resistant tuberculosis (MDR-TB) and 100,000 new patients with rifampicin-resistant tuberculosis (RR-TB) in 2015. Mortality was common in Asia with 250,000 deaths in the same year. 1 Treatment was successful in 52% of the MDR/RR-TB patients whereas 17% mortality and 9% treatment failure were reported. Extensively drug-resistant TB (XDR- TB) have acquired in 9.5% of MDR-TB cases with 117 countries have reported for XDR-TB in the world. 1 Treatment success rate was only 26% in XDR-TB cases. 1 Drug sensitive strains of TB need treatment duration of 6 months whereas MDR-TB and XDR-TB requires more than 20 months of treatment. 2 The burden of MDR-TB is increasing in various regions of the world. In the last 40 years after rifampicin has been started to be used in 1970s, no new anti- tuberculous drug was introduced. 2 The research for the development of new anti-tuberculous drugs is expensive and slow because the replication rate of tubercle bacilli takes time and the pharmaceutical manufacturers which are present in well-developed countries without TB burden have no much interest. 2 There was an increasing interest in the development of novel drugs with a different mechanism of action which can combat both drug-sensitive as well as drug-resistant strains of M. tuberculosis in last 10 years after global plan has been launched to stop TB. 2 Andries and co-workers at Janssen Pharmaceutical Company discovered bedaquiline, a new anti- tuberculosis (TB) drug and was approved by the US FDA in 2012 to treat MDR-TB as part of combination therapy. 2 Bedaquiline was known to have a novel mechanism of action with the effect on the metabolism of M. tuberculosis. 2 It inhibits mycobacterial ATP synthetase and is effective against both replicating and dormant organisms because ATP is still essential in dormant organisms for the survival. Although it has long half-life, early bactericidal activity of bedaquiline at the dose of 400 mg daily was nearly the same to 600 mg rifampicin and 300 mg isoniazid from 4th day onwards in the course of 7 days. 2 Phase II trials indicated that bedaquiline has been well tolerated by the patients and effcacy was good when it is used in combination with background regimen (BR) to treat MDR-TB. 2 Time of sputum conversion was shorter and percentage of sputum conversion was higher in both two months and six months phase trials. 2 Two black boxes were observed with bedaquiline, which are prolonged QT interval and higher mortality when compared with the placebo treatment 3 . Currently Phase III trials are on the way to verify its safety and effectiveness. 2, 3 Drug resistance mechanisms occur usually by means of horizontal transfer of plasmids or transposons carrying resistance genes between bacteria. 4 For antibiotics, it is feasible to identify resistance in bacteria only after market release. 4 However, drug resistance in the Mycobacterium tuberculosis emerged by chromosomal mutations. 4 The methods for detecting resistance mechanisms include identifying drug-resistant mutants in-vitro, in-vivo animal models and clinical trials. 4 Mutations in the ATP synthase associated with bedaquiline resistance have been found to emerge in the next-generation sequencing approach. Drug resistance was known 8 years after the mechanism of bedaquiline was well understood. 4 Subunit c of