Selected questions and controversies about bedaquiline: a view from the field

Although there has been a slow decline in tuberculosis (TB) incidence worldwide, the prevalence of drug-resistant TB in most high-burden countries has increased. Drug-resistant TB is associated with high mortality, is a threat to health care workers in TB-endemic countries and is prohibitively costly, which diverts resources away from drug-susceptible cases. Amplification of resistance means that there is an increasing proportion of patients with multidrug-resistant TB who have extensively drug-resistant TB (XDR-TB) or are programmatically untreatable. Thus, new treatment options are urgently needed. Bedaquiline (BDQ) is the first new drug specifically developed for TB to be licensed for use in almost 40 years. BDQ has sterilising activity and also shows promise as a component of new treatment-shortening regimens for drug-susceptible TB. Here we review insights from the field into the use of BDQ, issues relevant to the practising clinician, implications for the selection for antiretroviral therapy, pharmacokinetic issues relevant to clinical practice and implications for combination therapy. Given the increasing prevalence of resistance beyond XDR-TB, we also discuss how the development of resistance to BDQ can be minimised.