Treatment is successful in only 50–80% of cases of MDR-TB [5–7], and less than 50% of cases for XDR-TB [8]. In light of the limitations of existing therapy, the Global Plan to Stop TB has highlighted the importance of developing additional drug regimens that are effective against drug-resistant disease [9]. Bedaquiline (previously known as TMC207) is a novel member of the diarylquinoline class of anti-TB drugs. Following promising results in a number of pre-clinical and clinical studies, check details the drug was approved in 2012 by the US Food and Drug Administration (FDA) for use in the treatment of pulmonary MDR-TB [10]. An expert group

convened by the World Health Organization has also released interim policy recommendations regarding the use of bedaquiline as a part of treatment for pulmonary MDR-TB [11]. However, concerns have been raised about the drug’s effectiveness and safety [12, 13]. This review evaluates the available clinical evidence for the use of bedaquiline to treat drug-resistant TB. Methods A literature search was performed using PubMed, applying the search terms “bedaquiline” or “TMC207”

and “tuberculosis”, for studies published up to April 1, 2013. The full-text of articles was reviewed. The website of the US FDA was also searched for available data about bedaquiline, and data from publically available reports and submissions were included in this review. For comparisons between bedaquiline and placebo groups, if P values were not stated in the publication then they were calculated using Pearson’s χ 2 test or Fisher’s exact test. Selleck BTK inhibitor For studies where follow-up data were incomplete, outcomes were included Tau-protein kinase up to the stated cut-off reporting

dates. Mechanism of Action Bedaquiline is a diarylquinoline compound that specifically inhibits the proton pump of mycobacterial adenosine triphosphate (ATP) synthase, which is essential for mycobacterial energy generation [14, 15]. The drug is structurally and mechanistically different than fluoroquinolone antibiotics, and other related quinoline classes of drugs. This means that antibiotic resistance to fluoroquinolones, which are a part of standard treatment of MDR-TB, does not also confer resistance to bedaquiline [14]. Bedaquiline has bactericidal activity in vitro against M. tuberculosis as well as other mycobacterial species [14]. It inhibits both actively replicating and non-replicating mycobacteria, with one study showing inhibition of dormant cells in latent TB infection at a low concentration [16]. Mycobacterial susceptibility to the drug is unaltered in the presence of resistance to other anti-TB drugs, including isoniazid, rifampicin, ethambutol, streptomycin, ethambutol, and moxifloxacin [14]. Administration, Pharmacokinetics, and Pharmacodynamics Bedaquiline is given NF-��B inhibitor orally, reaching peak concentration 5 h after administration [14].