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.
Tuberculosis (Edinb). 2012 May;92(3):260-3. doi: 10.1016/j.tube.2012.01.005. Epub 2012 Feb 16.
Fluoroquinolones such as ofloxacin are promising drugs to treat drug-resistant tuberculosis (TB) and have been proposed for shortening the treatment of TB. The objectives were to study the synergistic effect of the combinations of three drugs and to evaluate the in vitro interactions of the following combinations against Mycobacterium tuberculosis: A) isoniazid, rifampicin, and ethambutol and B) ofloxacin, rifampicin, and ethambutol using an adaptation of the two-dimensional chequerboard assay. A total of 12 isolates resistant to isoniazid or to isoniazid-streptomycin and 11 drug-susceptible isolates were tested. The fractional inhibitory concentration (FICI) was calculated as follows: FICI = FIC(A) + FICB + FIC(C) = A/MIC(A) + B/MIC(B) + C/MIC(C) where A, B and C were the MICs of each antibiotic in combination and MIC(A), MIC(B) and MIC(C) were the individual MICs. The FICI was interpreted as synergism when the value was ≤0.75. In combination A, 11 drug-susceptible isolates decreased the individual MIC one to three dilutions, showing indifferent activity in 81.8% (FICI = 0.88-1.6) and synergistic activity in 18.1% (FICI = 0.6). In combination B, 21 out of the 23 isolates studied (91.3%) showed synergism (FICI = 0.31-0.62). In conclusion, adaptation of the two-dimensional chequerboard assay is a reliable method to study in vitro three-drug combinations. Both three-drug combinations tested may be useful against drug-resistant isolates, although the combination including ofloxacin showed better efficacy, being of potential use in drug-susceptible and isoniazid-resistant isolates.
氟喹诺酮类药物，如氧氟沙星，是治疗耐药结核病（TB）的有前途的药物，并被提议用于缩短结核病的治疗时间。目的是研究三种药物联合使用的协同作用，并使用二维棋盘试验的改编版评估以下组合对结核分枝杆菌的体外相互作用：A）异烟肼、利福平、乙胺丁醇和 B）氧氟沙星、利福平、乙胺丁醇。共测试了 12 株耐异烟肼或异烟肼-链霉素的分离株和 11 株药物敏感的分离株。分数抑制浓度（FICI）的计算方法如下：FICI = FIC（A）+ FICB + FICC = A/MIC（A）+ B/MIC（B）+ C/MIC（C），其中 A、B 和 C 是每种抗生素联合的 MIC，MIC（A）、MIC（B）和 MIC（C）是单个 MIC。当值≤0.75 时，FICI 被解释为协同作用。在组合 A 中，11 株药物敏感的分离株使个体 MIC 减少一到三个稀释度，在 81.8%（FICI = 0.88-1.6）的情况下表现出中性活性，在 18.1%（FICI = 0.6）的情况下表现出协同活性。在组合 B 中，研究的 23 个分离株中的 21 个（91.3%）显示出协同作用（FICI = 0.31-0.62）。总之，二维棋盘试验的改编是研究体外三药联合的可靠方法。两种三药联合可能对耐药分离株有效，尽管包含氧氟沙星的联合方案显示出更好的疗效，对药物敏感和异烟肼耐药的分离株具有潜在用途。
