aJohns Hopkins University School of Medicine, Baltimore, Maryland, USA bStellenbosch University, Tygerberg, South Africa.
Curr Opin HIV AIDS. 2013 Nov;8(6):579-85. doi: 10.1097/COH.0000000000000009.
For the first time in decades, there are multiple new drugs in the pipeline for the treatment of tuberculosis (TB). In addition, existing drugs are being repurposed or optimized for TB with the goal of shortened treatment duration for drug-sensitive TB and safer, shorter treatments for multidrug-resistant (MDR) TB. In this review, the results of recent trials evaluating novel combination regimens for TB disease and latent TB infection are described.
High-dose rifamycins (rifampin and rifapentine) and fluoroquinolones directly observed have treatment-shortening potential when used for drug-sensitive TB disease, and a 12-dose once-weekly regimen of rifapentine along with isoniazid effectively treats latent TB. Bedaquiline, an anti-TB drug with a novel mechanism of action, and delamanid, a nitroimidazole, are entering phase 3 trials. Both improve rates of sputum culture conversion among patients with MDR-TB. Other nitroimidazoles and oxazolidinones are in Phase 2 testing, as are combinations involving multiple new chemical entities.
With the resurgence of anti-TB drug discovery efforts, we now have a modestly robust pipeline of new anti-TB drugs. Several promising new regimens involving investigational and existing drugs that may be capable of shortening treatment for drug-sensitive TB and improving management of drug-resistant TB are in late-phase clinical evaluation.
几十年来,首次有多种新型药物进入结核病(TB)治疗领域。此外,正在重新开发或优化现有药物,以缩短药物敏感性结核病的治疗时间,并为耐多药结核病(MDR-TB)提供更安全、更短的治疗方案。在本次综述中,描述了最近评估新型联合治疗方案治疗结核病和潜伏性结核感染的试验结果。
高剂量利福平(利福平和利福喷丁)和氟喹诺酮类药物经直接观察,在治疗药物敏感性结核病疾病时具有缩短治疗时间的潜力,而每周一次使用利福喷丁联合异烟肼的 12 剂方案可有效治疗潜伏性结核。贝达喹啉,一种具有新型作用机制的抗结核药物,和德拉马尼,一种硝基咪唑,正在进行 3 期试验。两者均能提高 MDR-TB 患者的痰培养转化率。其他硝基咪唑和恶唑烷酮类药物正在进行 2 期试验,同时也在进行涉及多种新型化学实体的联合用药试验。
随着抗结核药物研发工作的复苏,我们现在拥有了适度强大的新型抗结核药物研发管道。几种有前途的新型方案涉及研究中的和现有的药物,这些药物可能有能力缩短药物敏感性结核病的治疗时间,并改善耐药结核病的管理,这些方案正在进行后期临床评估。