Safety and efficacy of exposure to bedaquiline-delamanid in multidrug-resistant tuberculosis: a case series from France and Latvia

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) represent a therapeutic challenge [1]. Two anti-TB agents, bedaquiline and delamanid, have been recently approved for the treatment of MDR/XDR-TB. Bedaquiline has a terminal half-life of 5.5 months, in contrast with the short half-life of delamanid (38 h). Both drugs increase the QTcF (Fridericia-corrected QT) interval, although no clinically significant cardiac events have been reported in patients treated with one of these drugs [2, 3]. The clinical trials that led to approval of bedaquiline and delamanid tested these drugs by adding one of them, for a duration of 24 weeks and 6–8 months, respectively, to optimised background [2, 3]. To date, only six cases treated with the bedaquiline−delamanid combination have been reported, mostly presenting interim results [4–6]. The World Health Organization (WHO) recommends to use these drugs for a standardised duration of 24 weeks, the concomitant use of bedaquiline and delamanid being restricted to patients with “no other therapeutic options”. Otherwise, it is recommended to start the two drugs sequentially after a washout period of 6 months, when switching from bedaquiline to delamanid, and 5 days, when switching from delamanid to bedaquiline [7]. We report the results of exposure to concomitant and sequential treatment with bedaquiline and delamanid, including treatment courses beyond 24 weeks, as part of multidrug MDR/XDR-TB regimens.