Bedaquiline

Bedaquiline (previously R207910, then TMC207) is a firstin- class diarylquinolone antibiotic that was initially approved for the treatment of multidrug-resistant tuberculosis (MDR-TB), tuberculosis (TB) resistant to isoniazid and rifampicin, by the US Food and Drug Admin istration (FDA) in 2012 and the European Medicines Agency (EMA) in 2014. It is currently recommended for use by the World Health Organization (WHO) for patients with MDR-TB who lack other treatment options (WHO, 2013); it is commonly used in patients infected with TB that is extensively drug resistant (XDR) (resistant to isoniazid, rifampicin, fluoroquinolones, and injectable agents). Bedaquiline causes QT interval prolongation, as do several second-line anti-TB drugs, so caution must be exercised when designing a combination antimicrobial regimen that includes beda quiline (Janssen Products, 2015). In addition, bedaquiline was registered in several countries after a phase II trial data demonstrated the microbiologic activity of this agent (Diacon et al., 2014) prior to the availability of phase III trial results. This expedited approval was granted in large part because of the great unmet medical need for drugs to treat MDR- and XDR-TB. In the small phase II randomized clinical trial, though, mortality was higher in the bedaquiline than in the placebo arm (Diacon et al., 2014). This “mortality imbalance” remains unexplained-deaths often occurred late (after completion of bedaquiline treatment), causes of death were widely variable, and mortality in the placebo arm was surprisingly low-and has complicated this drug’s introduction globally. Up to now, higher-than-expected mortality has not been seen in post-marketing pharmacovigilance studies (Ndjeka et al., 2015).