Servei de Microbiologia, CDB, Hospital Clínic de Barcelona - ISGlobal, Universitat de Barcelona, c/ Villarroel 170, 08036 Barcelona, Spain.
Servei de Microbiologia, CDB, Hospital Clínic de Barcelona - ISGlobal, Universitat de Barcelona, c/ Villarroel 170, 08036 Barcelona, Spain.
Int J Antimicrob Agents. 2015 Nov;46(5):582-5. doi: 10.1016/j.ijantimicag.2015.08.004. Epub 2015 Sep 7.
Multidrug resistance has become a problem in the management of tuberculosis, with an urgent need for research into new drugs as well as the development of efficacious drug combinations and regimens. The main objective of this study was to assess and compare the efficacy of three antituberculous combinations (clofazimine/pretomanid/levofloxacin, clofazimine/pretomanid/moxifloxacin and clofazimine/pretomanid/UB-8902) against multidrug-resistant (MDR) and drug-susceptible clinical isolates of Mycobacterium tuberculosis using an in vitro adaptation of the chequerboard assay. A total of 7 MDR and 11 drug-susceptible clinical isolates were studied. The fractional inhibitory concentration index (FICI) was interpreted as synergism when the value was <0.75, antagonism when it was >4 and additive activity between these two values. The FICI of all of the combinations ranged from 1.2 to 2.3, showing additive activity against all of the isolates. No differences were found between MDR and drug-susceptible isolates. In conclusion, the three combinations are effective against M. tuberculosis with equal effects. Moreover, in vitro testing of drug combinations could be useful to predict their clinical use.
多药耐药性已成为结核病管理中的一个问题，迫切需要研究新的药物以及开发有效的药物组合和方案。本研究的主要目的是使用棋盘微量稀释法评估和比较三种抗结核组合（氯法齐明/普托马尼/左氧氟沙星、氯法齐明/普托马尼/莫西沙星和氯法齐明/普托马尼/UB-8902）对耐多药（MDR）和药敏临床分离株结核分枝杆菌的疗效。共研究了 7 株 MDR 和 11 株药敏临床分离株。当分数抑制浓度指数（FICI）值<0.75 时，被解释为协同作用；当值>4 时，被解释为拮抗作用；而在这两个值之间则为相加作用。所有组合的 FICI 范围为 1.2 至 2.3，对所有分离株均表现出相加作用。MDR 和药敏分离株之间未发现差异。总之，三种组合对结核分枝杆菌有效，作用相当。此外，药物组合的体外测试可能有助于预测其临床应用。
