结核分枝杆菌德拉马尼和PA-824耐药相关机制研究进展

结核病仍是全球十大死因之一,而耐药结核病的出现,给全球结核病的防控工作带来了极大的困难与挑战。德拉马尼和PA-824(Pretomanid)同为硝基咪唑类抗结核药物,对耐多药结核病及广泛耐药结核病均有较好的疗效,尤其是PA-824与贝达喹啉和利奈唑胺组成的BPaL方案对高度耐药的结核病患者具有更高的治愈率。但近年来有研究表明,结核分枝杆菌(Mycobacterium tuberculosis, MTB)对德拉马尼和PA-824已经出现了耐药现象。准确及时的对德拉马尼和PA-824耐药菌株进行检测,可有效避免耐药现象的加剧并提高药物的临床应用效果。本文综述了MTB对德拉马尼和PA-824耐药的机制及相关基因突变情况,以期为今后德拉马尼和PA-824耐药株的快速检测及其在临床上的合理应用提供参考。

Progress on the molecular mechanism of delamanid and PA-824 resistance in Mycobacterium tuberculosis

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is still one of the top ten causes of death in the world, especially with the presence of drug resistant tuberculosis, which has caused great challenges for tuberculosis control. Both delamanid and PA-824 (Pretomanid) are nitroimidazole anti-TB drugs that have had a good effectiveness in the treatment of multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis. Furthermore, the BPaL regimen that consists of PA-824, bedaquiline and linezolid, has a better cure rate for highly drug resistant TB cases. However, MTB with resistance to delamanid and PA-824 have been observed in recent years. Rapid examination of MTB resistance to delamanid and PA-824 could effectively avoid the aggravation of drug resistance and improve their clinical application. This study reviewed the resistance related genes of MTB to delamanid and PA-824, in order to provide a reference for the rapid diagnosis of drug resistance to delamanid and PA-824 in MTB and for their continued application in clinical treatment.