In 2012, the U.S. Food and Drug Administration approved bedaquiline for treating drug-resistant tuberculosis—the first new type of TB drug approved in 40 years. Bedaquiline is administered in combination with at least four other drugs and has transformed the treatment of multidrug- and extensively drug-resistant (M/XDR) TB. However, combination therapy for M/XDR TB must last 1-2 years and is associated with many serious side effects. As a result, up to 25 percent of patients stop treatment early. Bedaquiline has a much longer half-life in the body than the drugs it’s combined with, so a halt in treatment means that bedaquiline persists alone in the bloodstream for many months. With other drugs no longer present to combat them, the TB bacteria can become resistant to bedaquiline.

James Brust, M.D., was awarded a five-year, $3.6 million grant from the National Institutes of Health (NIH) to investigate the development of resistance to bedaquiline after therapy with the drug is interrupted. The study involves a cohort of patients in South Africa with M/XDR TB— the largest bedaquiline treatment program in the world—and will address fundamental questions about bedaquiline pharmacology and resistance. The study includes collaborations with the University of Cape Town, Stellenbosch University and Emory University. 

Dr. Brust is an associate professor of medicine at Einstein and attending physician at Montefiore Health System. (R01AI145679)