Clinical Medicine Insights: Therapeutics

Globally, the incidence of tuberculosis (TB) is declining but the proportion of drug-resistant cases has increased. Strains resistant to both isoniazid and rifampin, and possibly other antibiotics, called multidrug-resistant (MDR), are particularly difficult to treat. Poorer outcomes, including increased mortality, occur in patients infected with MDR strains and the costs associated with treatment of MDR-TB are substantially greater. The recent recognition of MDR-TB and strains with more complex resistance patterns has stimulated the development of new TB medications including fluoroquinolones, oxazolidinones, diarylquinolines, nitroimidazopyrans, ethylenediamines, and benzothiazinones. Bedaquiline, a diarylquinoline, was approved for the treatment of MDR-TB in 2012. Addition of delamanid to WHO-approved treatment improved outcomes for MDR-TB and for extensively drug-resistant TB in a large randomized, controlled phase II clinical trial and is undergoing evaluation in a large international phase III study. This review will focus on MDR-TB and the role of delamanid in its treatment.