AIRF & Special Centre for Nano Sciences, Jawaharlal Nehru University, New Delhi, India.
IFTM University, Moradabad, Uttar Pradesh, India.
J Appl Microbiol. 2020 Jun;128(6):1547-1567. doi: 10.1111/jam.14478. Epub 2019 Oct 29.
Tuberculosis (TB) along with acquired immune deficiency syndrome and malaria rank among the top three fatal infectious diseases which pose threat to global public health, especially in middle and low income countries. TB caused by Mycobacterium tuberculosis (Mtb) is an airborne infectious disease and one-third of the world's population gets infected with TB leading to nearly 1·6 million deaths annually. TB drugs are administered in different combinations of four first-line drugs (rifampicin, isoniazid, pyrazinamide and ethambutol) which form the core of treatment regimens in the initial treatment phase of 6-9 months. Several reasons account for the failure of TB therapy such as (i) late diagnosis, (ii) lack of timely and proper administration of effective drugs, (iii) lower availability of less toxic, inexpensive and effective drugs, (iv) long treatment duration, (v) nonadherence to drug regimen and (vi) evolution of drug-resistant TB strains. Drug-resistant TB poses a significant challenge to TB therapy and control programs. In the background of worldwide emergence of 558 000 new TB cases with resistance to rifampicin in the year 2017 and of them, 82% becoming multidrug-resistant TB (MDR-TB), it is essential to continuously update the knowledge on the mechanisms and molecular basis for evolution of Mtb drug resistance. This narrative and traditional review summarizes the progress on the anti-tubercular agents, their mode of action and drug resistance mechanisms in Mtb. The aim of this review is to provide recent updates on drug resistance mechanisms, newly developed/repurposed anti-TB agents in pipeline and international recommendations to manage MDR-TB. It is based on recent literature and WHO guidelines and aims to facilitate better understanding of drug resistance for effective TB therapy and clinical management.
结核病（TB）与获得性免疫缺陷综合征和疟疾一起，构成了对全球公共卫生构成威胁的三大致命传染病，尤其是在中低收入国家。由结核分枝杆菌（Mtb）引起的结核病是一种空气传播的传染病，全球有三分之一的人口感染了结核病，导致每年近 160 万人死亡。结核病药物以四种一线药物（利福平、异烟肼、吡嗪酰胺和乙胺丁醇）的不同组合形式给药，这些药物构成了 6-9 个月初始治疗阶段治疗方案的核心。结核病治疗失败的原因有很多，包括：（i）诊断较晚，（ii）未能及时、恰当地使用有效药物，（iii）毒性较低、价格低廉且有效的药物供应不足，（iv）治疗时间长，（v）不遵守药物治疗方案，以及（vi）耐药结核菌株的出现。耐药结核病对结核病治疗和控制计划构成了重大挑战。在全球范围内，2017 年新出现了 55.8 万例对利福平耐药的结核病病例，其中 82%成为耐多药结核病（MDR-TB），因此，不断更新对结核分枝杆菌耐药性演变的机制和分子基础的认识至关重要。本综述和传统综述总结了抗结核药物及其在 Mtb 中的作用机制和耐药机制方面的进展。本综述的目的是提供耐药机制的最新进展、新开发/重新用于抗结核药物的药物和管理耐多药结核病的国际建议。它基于最近的文献和世卫组织的指南，旨在帮助更好地理解耐药性，以实现有效的结核病治疗和临床管理。
