Servei de Microbiologia, CDB, Hospital Clínic de Barcelona-Barcelona Centre for International Health Research-CRESIB, Dpt. Anatomia Patològica, Farmacologia i Microbiologia, Universitat de Barcelona-UB, Barcelona, Spain.
Int J Antimicrob Agents. 2013 Mar;41(3):278-80. doi: 10.1016/j.ijantimicag.2012.11.011. Epub 2013 Jan 9.
Multidrug resistance has become a problem in the management of tuberculosis, leading to an urgent need for research related to new regimens including the currently available drugs. The objectives of this study were: (i) to study the effect of the following second-choice three-drug combinations against multidrug-resistant (MDR) and drug-susceptible clinical isolates (levofloxacin, linezolid and ethambutol; levofloxacin, amikacin and ethambutol; and levofloxacin, linezolid and amikacin); and (ii) to compare the effect of these combinations with an isoniazid, rifampicin and ethambutol combination against drug-susceptible clinical isolates. A total of 9 MDR clinical and 12 drug-susceptible isolates (11 clinical isolates and the H37Rv reference strain) were studied using an adaptation of the chequerboard assay. The fractional inhibitory concentration index (FICI) was calculated as follows: FICI=FIC(A)+FIC(B)+FIC(C)=A/MIC(A)+B/MIC(B)+C/MIC(C), where A, B and C are the minimum inhibitory concentrations (MICs) of each antibiotic in combination and MIC(A), MIC(B) and MIC(C) are the individual MICs. The FICI was interpreted as synergism when the value was <0.75. The FICI of all the combinations ranged from 1.5 to 3, showing indifferent activity. No differences were found between MDR and drug-susceptible isolates, or between the second-choice combinations and the fourth combination against drug-susceptible isolates. In conclusion, the second-choice drugs are equally effective as the combination of isoniazid, rifampicin and ethambutol.
多药耐药性已成为结核病管理中的一个问题，因此迫切需要研究新的治疗方案，包括目前可用的药物。本研究的目的是：（i）研究以下三种二线三药组合对耐多药（MDR）和药敏临床分离株（左氧氟沙星、利奈唑胺和乙胺丁醇；左氧氟沙星、阿米卡星和乙胺丁醇；左氧氟沙星、利奈唑胺和阿米卡星）的作用；（ii）比较这些组合与异烟肼、利福平、乙胺丁醇组合对药敏临床分离株的作用。共研究了 9 株 MDR 临床分离株和 12 株药敏分离株（11 株临床分离株和 H37Rv 参考株），采用棋盘微量稀释法进行了适应性研究。计算部分抑菌浓度指数（FICI）如下：FICI=FIC（A）+FIC（B）+FIC（C）=A/MIC（A）+B/MIC（B）+C/MIC（C），其中 A、B 和 C 是联合使用的每种抗生素的最小抑菌浓度（MIC），MIC（A）、MIC（B）和 MIC（C）是各单独 MIC。当值<0.75 时，FICI 被解释为协同作用。所有组合的 FICI 范围为 1.5 至 3，显示出中性活性。未发现 MDR 和药敏分离株之间、二线组合与药敏分离株的第四种组合之间存在差异。总之，二线药物与异烟肼、利福平、乙胺丁醇的组合同样有效。
