Bedaquiline for the Treatment of Multidrug-Resistant Tuberculosis in the United States

BACKGROUND: In 2012, the Food and Drug Administration approved the use of bedaquiline fumarate as part of combination therapy for treatment of multidrug-resistant tuberculosis (MDR TB). We describe the treatment outcomes, safety, and tolerability of bedaquiline in our case series. METHODS: Data on patients started on bedaquiline for MDR TB between September 2012 and August 2016 were collected retrospectively through four TB programs using a standardized abstraction tool. Data were analyzed using univariate methods. Adverse events were graded using the Common Terminology Criteria for Adverse Events. RESULTS: Of 14 patients in this case series, 7/14 (50%) had MDR, 4/14 (29%) had pre-extensively-drug-resistant (XDR), and 3/14 (21%) had XDR. All had pulmonary TB, 5/14 (36%) had pulmonary and extrapulmonary TB, and 9/13 (69%) were smear-positive. One patient (7%) had HIV co-infection, 5/14 (36%) had diabetes mellitus, and 5 (36%) had been previously treated for TB. All patients were non-U.S.-born and 5 (36%) had private insurance. All patients achieved sputum culture conversion within a mean of 71 days (26-116); 6/14 after starting bedaquiline. Twelve (86%) completed treatment and 1/14 (7%) moved out of the country. One patient (7%) had QTc prolongation >500 milliseconds and died 20 months after discontinuing bedaquiline of a cause not attributable to the drug. The most common adverse events were peripheral neuropathy (50%), not customarily associated with bedaquiline use, and QTc prolongation (43%). CONCLUSIONS: Of 14 patients, one had an adverse event necessitating bedaquiline discontinuation. Safety, culture conversion, and treatment completion in this series support use of bedaquiline for the treatment of MDR/XDR TB.