Bedaquiline: how better to use it

From the authors:

We read with interest the correspondence by J. Furin and co-workers and we wish to thank them for their useful comments on our editorial proposing a rationale for a standardised regimen to manage difficult-to-treat cases affected by extensively drug-resistant tuberculosis (XDR-TB) or by so-called pre-extensively drug-resistant tuberculosis (pre-XDR; multidrug-resistant tuberculosis (MDR-TB) cases with additional resistance to fluoroquinolones or second-line injectable drugs) [1]. We agree with the comments by Furin and co-workers and the arguments discussing the possible use of the new drugs (bedaquiline and/or delamanid) for more than 6 months. Clinicians know very well how difficult it is to manage the treatment of these cases in view of their clinical complexity (with frequent adverse events), long duration and high cost [2–4]. Considering the new perspectives for treating MDR-TB and XDR-TB we fully agree that we are presently facing exciting times. We finally have a couple of new and repurposed drugs and we are slowly discovering how best to use them, as well as how effective and safe they are [4–7]. The necessary body of knowledge to support evidence-based recommendations will need time to be raised and this is reflected by the increase in new proposals and recommendations being issued [8, 9]. Among the different ingredients for a potential, future standardised regimen for MDR/XDR-TB cases, the biological plausibility of the core drugs to be used (bactericidal and sterilising) is particularly important (table 1) [1]. As both bedaquiline and delamanid have excellent characteristics, both their prolonged and/or combined use will be challenges that will need to be faced in the future. Slowly but surely new evidence is becoming available [2, 3] and we are confident that, given the high morbidity and mortality caused by MDR/XDR-TB, as well as the collaborative spirit animating clinicians, public health officers, policy makers, donors and members of the affected communities, better evidence will be raised to always ensure that the patient is adequately protected. Finally, the “off-label” use of drugs is sometimes necessary to manage patients for whom no other alternatives exist. Their use requires adequate capacity in terms of clinical expertise, laboratory support and infection control measures. We therefore hope that our proposal will soon be supported by the necessary evidence so as to be useful, safe and effective.