Cardiac safety of extensively drug-resistant tuberculosis regimens including bedaquiline, delamanid and clofazimine

I read with interest the recent article by Tadolini et al. [1] describing QT (ECG Q-T wave interval) prolongation in a patient with extensively drug-resistant tuberculosis (XDR-TB) being treated with both bedaquiline and delamanid. QT prolongation is a recognised safety concern for both these drugs. In a placebo-controlled trial of delamanid in multidrug resistant-TB, QTcF intervals (using the correction for heart rate of Fridericia [2]) increased 12.1 ms more from baseline in delamanid recipients over 6–10 weeks [3]. An increase of similar magnitude was observed in an open-label 24-week trial of bedaquiline, with most of the effect becoming apparent within the first 1–2 weeks [4]. The authors are correct that there is currently no clinical information regarding QT prolongation when these two drugs are co-administered. Clofazimine prolongs the QT interval and can potentiate the QT effects of other MDR-TB drugs