Division of Infection and Immunity, University College London and National Institute for Health Research (NIHR) Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK; UNZA-UCLMS Research and Training Project, University Teaching Hospital, Lusaka, Zambia.
Kenya Medical Research Institute, Nairobi, Kenya.
Lancet Respir Med. 2015 Mar;3(3):220-34. doi: 10.1016/S2213-2600(15)00063-6. Epub 2015 Mar 9.
WHO estimates that 9 million people developed active tuberculosis in 2013 and 1·5 million people died from it. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis continue to spread worldwide with an estimated 480,000 new cases in 2013. Treatment success rates of MDR and XDR tuberculosis are still low and development of new, more effective tuberculosis drugs and adjunct therapies to improve treatment outcomes are urgently needed. Although standard therapy for drug-sensitive tuberculosis is highly effective, shorter, more effective treatment regimens are needed to reduce the burden of infectious cases. We review the latest WHO guidelines and global recommendations for treatment and management of drug-sensitive and drug-resistant tuberculosis, and provide an update on new drug development, results of several phase 2 and phase 3 tuberculosis treatment trials, and other emerging adjunct therapeutic options for MDR and XDR tuberculosis. The use of fluoroquinolone-containing (moxifloxacin and gatifloxacin) regimens have failed to shorten duration of therapy, and the new tuberculosis drug pipeline is sparse. Scale-up of existing interventions with increased investments into tuberculosis health services, development of new antituberculosis drugs, adjunct therapies and vaccines, coupled with visionary political leadership, are still our best chance to change the unacceptable status quo of the tuberculosis situation worldwide and the growing problem of drug-resistant tuberculosis.
世界卫生组织估计,2013 年有 900 万人患有活动性结核病,150 万人因此死亡。耐多药(MDR)和广泛耐药(XDR)结核病继续在全球蔓延,2013 年估计有 48 万例新发病例。MDR 和 XDR 结核病的治疗成功率仍然较低,迫切需要开发新的、更有效的结核病药物和辅助治疗方法来改善治疗效果。虽然针对敏感结核病的标准治疗非常有效,但需要更短、更有效的治疗方案来减少传染性病例的负担。我们回顾了最新的世界卫生组织针对敏感和耐药结核病治疗和管理的指南和全球建议,并提供了新药物开发的最新信息、几项 2 期和 3 期结核病治疗试验的结果,以及针对 MDR 和 XDR 结核病的其他新出现的辅助治疗选择。含氟喹诺酮类(莫西沙星和加替沙星)方案未能缩短治疗时间,新的结核病药物研发管线匮乏。通过增加对结核病卫生服务的投资,扩大现有干预措施的规模,开发新的抗结核药物、辅助治疗和疫苗,加上有远见的政治领导,这仍然是我们改变全球结核病状况和日益严重的耐药结核病问题不可接受现状的最佳机会。