Office of Critical Path Programs, US FDA, Room 14B45, 5600 Fishers Lane, Rockville, MD 20857, USA.
Future Med Chem. 2009 Jul;1(4):749-56. doi: 10.4155/fmc.09.53.
Despite efficacious drugs for treatment, TB continues to affect enormous numbers of patients throughout the world. Failure to control TB may be related to the biological characteristics of Mycobacterium tuberculosis, the nature of susceptible hosts often impoverished and poorly supported by healthcare infrastructure and the complex treatment regimens that must be used. Challenges to anti-TB drug development include the organism's slow replication, the ability of M. tuberculosis to survive in a dormant state and to persist despite therapy, its impregnable cell wall and its capacity to develop resistance to drugs. The need for extended therapy using combinations of drugs remains a practical obstacle to effective control in poor, malnourished and diseased communities most susceptible to TB. High-throughput screening of candidate agents and investigation of drugs already in use for other infections are yielding promising new candidates for TB treatment. New families of drugs entering clinical trials include 5-nitroimidazoles, diarylquinolines and ethylene diamines. Increasing funding initiatives, advances in the biology of TB and strategies for drug discovery have rejuvenated the pipeline of new drugs for TB, promising an expanding armamentarium of effective drugs with improved tolerability and potential to treat drug-resistant cases.
尽管有有效的治疗药物，但结核病仍在全球范围内影响着大量患者。未能控制结核病可能与结核分枝杆菌的生物学特性、易感染宿主的性质有关，这些宿主往往生活在贫困和医疗基础设施支持不足的环境中，并且必须使用复杂的治疗方案。抗结核药物开发面临的挑战包括该生物的缓慢复制、结核分枝杆菌在休眠状态下生存并在治疗后持续存在的能力、其坚不可摧的细胞壁以及对药物产生耐药性的能力。在最容易感染结核病的贫穷、营养不良和患病社区中，使用药物联合进行长期治疗仍然是有效控制的实际障碍。对候选药物进行高通量筛选以及对用于治疗其他感染的药物进行研究，为结核病治疗带来了有前途的新候选药物。正在进入临床试验的新药物家族包括 5-硝基咪唑类、二芳基喹啉类和乙二胺类。增加资金投入、结核病生物学的进步以及药物发现策略，使结核病新药的研发管道重新焕发活力，有望为耐多药病例提供更有效、耐受性更好、有潜力的治疗药物。
