The US Food and Drug Administration has issued a black-box warning for bedaquiline, which improves treatment results in patients with rifampin-resistant (RR) tuberculosis but prolongs the QT interval. Although the World Health Organization advises bedaquiline for all patients with RR tuberculosis, no phase 3 clinical trial demonstrating its cardiac safety has been reported. The researchers conducted an observational cohort analysis of patients, from three provinces in South Africa, with RR tuberculosis who received bedaquiline-containing regimens. During bedaquiline therapy, researchers did extensive cardiac surveillance, which included taking electrocardiograms in triplicate at four-time points. Participants were tracked for a total of 24 months or until the end of therapy. Final tuberculosis treatment result and QT interval prolongation (QT prolongation) were measured. QT prolongation was defined as a QT interval adjusted by the Fridericia technique (QTcF)  greater than 500 ms or an absolute change from baseline (QTcF)  greater than 60 ms. The researchers enrolled 195 people who were eligible, with 40% of them having drug-resistant tuberculosis. The majority of the individuals (97%) were given clofazimine at the same time. 74% of the subjects were cured or successfully finished therapy, and outcomes were unaffected by the presence of the human immunodeficiency virus. Throughout bedaquiline treatment, QTcF increased, with a mean increase (standard deviation) of 23.7 (22.7) ms from baseline to month 6. A QTcF greater than 500 ms was experienced by four people, while a QTcF greater than 60 ms was experienced by 19 others. QT prolongation was linked to getting older on its own. QT prolongation was not more common or severe in those using lopinavir and ritonavir at the same time. Severe QT prolongation was infrequent and did not necessitate stopping bedaquiline or clofazimine for good. In older patients, it may be necessary to keep a close eye on the QT interval.

 

Link:academic.oup.com/cid/article/73/11/2083/6244470