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. Reflections on the best possible use of bedaquiline http://ow.ly/JiFL30fBZaQ

中文翻译：

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贝达喹啉：如何更好地使用它

我们饶有兴趣地阅读了 J. Furin 及其同事的来信，并感谢他们对我们的社论提出的有益评论，提出了标准化方案来管理受广泛耐药性结核病影响的难以治疗的病例的基本原理。 XDR-TB）或所谓的广泛耐药结核病（pre-XDR；耐多药结核病 (MDR-TB) 病例对氟喹诺酮类药物或二线注射药物具有额外耐药性）[1]。我们同意 Furin 和同事的评论以及讨论可能使用新药（贝达喹啉和/或德拉马尼）超过 6 个月的论点。鉴于这些病例的临床复杂性（不良事件频繁）、持续时间长和成本高，临床医生非常清楚管理这些病例的治疗是多么困难 [2-4]。考虑到治疗耐多药结核病和广泛耐药结核病的新观点，我们完全同意我们目前正面临激动人心的时刻。我们终于有了一些新的和重新利用的药物，我们正在慢慢发现如何最好地使用它们，以及它们的有效性和安全性 [4-7]。需要时间来提出支持循证建议的必要知识体系，这反映在新提议和建议的增加上 [8, 9]。在 MDR/XDR-TB 病例潜在的、未来标准化方案的不同成分中，要使用的核心药物(杀菌和灭菌)的生物学合理性尤为重要(表 1)[1]。由于贝达喹啉和德拉马尼都具有优异的特性，它们的长期和/或联合使用将是未来需要面对的挑战。新的证据正在缓慢但肯定地出现 [2, 3] 并且我们相信，鉴于耐多药/广泛耐药结核病引起的高发病率和死亡率，以及激发临床医生、公共卫生官员、决策者、捐助者的合作精神和受影响社区的成员，将提出更好的证据，以始终确保患者得到充分保护。最后，有时需要“标签外”使用药物来管理没有其他替代品的患者。它们的使用需要在临床专业知识、实验室支持和感染控制措施方面有足够的能力。因此，我们希望我们的建议能很快得到必要的证据支持，从而做到有用、安全和有效。