University Medical Center Groningen, Dept of Hospital and Clinical Pharmacy, Groningen.
Eur Respir J. 2014 Mar;43(3):884-97. doi: 10.1183/09031936.00113713. Epub 2013 Aug 29.
Treatment of multidrug-resistant (MDR) tuberculosis (TB) is challenging because of the high toxicity of second-line drugs and the longer treatment duration than for drug-susceptible TB patients. In order to speed up novel treatment for MDR-TB, we suggest considering expanding the indications of already available drugs. Six drugs with antimicrobial activity (phenothiazine, metronidazole, doxycycline, disulfiram, tigecycline and co-trimoxazole) are not listed in the World Health Organization guidelines on MDR-TB treatment but could be potential candidates for evaluation against Mycobacterium tuberculosis. A systematic review was conducted to evaluate antituberculous activity of these drugs against M. tuberculosis. We searched PubMed, Google Scholar and Embase for English articles published up to December 31, 2012. We reviewed in vitro, in vivo and clinical antituberculous activity of these drugs in addition to pharmacokinetics and side-effects. Of the drugs effective against actively replicating M. tuberculosis, co-trimoxazole seems to be the most promising, because of its consistent pharmacokinetic profile, easy penetration into tissue and safety profile. For the dormant state of TB, thioridazine may play a potential role as an adjuvant for treatment of MDR-TB. A strategy consisting of pharmacokinetic/pharmacodynamic studies, dose finding and phase III studies is needed to explore the role of these drugs in MDR-TB treatment.
耐多药结核病（MDR-TB）的治疗具有挑战性，因为二线药物毒性高，且治疗时间长于对药物敏感的结核病患者。为了加快耐多药结核病的新疗法，我们建议考虑扩大现有药物的适应证。有 6 种具有抗菌活性的药物（吩噻嗪、甲硝唑、强力霉素、双硫仑、替加环素和复方磺胺甲噁唑）不在世界卫生组织耐多药结核病治疗指南中，但可能是针对结核分枝杆菌评估的潜在候选药物。我们进行了系统评价，以评估这些药物对结核分枝杆菌的抗结核活性。我们检索了截至 2012 年 12 月 31 日发表的英文文章，检索PubMed、Google Scholar 和 Embase。我们评估了这些药物的体外、体内和临床抗结核活性，以及药代动力学和副作用。在有效对抗活跃复制的结核分枝杆菌的药物中，复方磺胺甲噁唑似乎最有前途，因为其药代动力学特征一致、易于渗透到组织中且安全性良好。对于结核病的休眠状态，噻嗪可能作为治疗耐多药结核病的辅助药物发挥作用。需要进行药代动力学/药效学研究、剂量发现和 III 期研究的策略，以探索这些药物在耐多药结核病治疗中的作用。
