JMI Laboratories, North Liberty, IA 52317, USA.
Diagn Microbiol Infect Dis. 2010 Mar;66(3):301-7. doi: 10.1016/j.diagmicrobio.2009.10.014.
Fusidic acid (CEM-102) is a steroidal antimicrobial agent with focused Gram-positive activity that acts by preventing bacterial protein synthesis via interacting with elongation factor G. A collection of 114 wild-type isolates (> 80 species) was used to define the contemporary limits of fusidic acid spectrum against Gram-positive and Gram-negative species. Reference broth microdilution and anaerobic agar dilution methods were performed. Modifications of standardized test methods included adding 10% human serum and adjusting the medium pH to 5, 6, and 8. Synergy was assessed by the checkerboard method and time-kill studies. Mutational rates to resistance were determined at 4 x, 8 x, and 16 x MIC. Against Gram-positive pathogens, fusidic acid MIC values ranged from 0.06 to 32 microg/mL with the greatest potency against Staphylococcus aureus, Corynebacterium spp., and Micrococcus luteus (MIC results, 0.25, < or = 0.12, and < or = 0.5 microg/mL, respectively). Enterococci and streptococci were less susceptible (MIC ranges, 2-8 and 16-32 microg/mL, respectively). Fusidic acid activity against Gram-negative species was more limited (all MIC values, > or = 2 microg/mL) except for Empedobacter brevis, Moraxella catarrhalis and Neisseria meningitidis. A 4-fold increase in fusidic acid MIC results was observed when 10% serum was added to the broth. Decreasing medium pH to 5.0 to 6.0 negated the protein binding effects. Among the 8 antimicrobial combinations tested, gentamicin and rifampin enhanced the activity when combined with fusidic acid (no antagonism). Fusidic acid in vitro activity was most improved when combined with rifampin. Single-step mutational rates ranged from 1.2 x 10(-6) for 4x MIC to 9.8 x 10(-8) for 16 x MIC. In conclusion, these in vitro results for fusidic acid tested against contemporary strains confirm a persisting antimicrobial spectrum, especially against staphylococci and some other Gram-positive species.
夫西地酸（CEM-102）是一种具有特定革兰氏阳性活性的甾体类抗菌药物，通过与延伸因子 G 相互作用来阻止细菌蛋白质合成，从而发挥作用。收集了 114 株野生型分离株（>80 种），以确定夫西地酸对革兰氏阳性和革兰氏阴性物种的当代谱范围。进行了参考肉汤微量稀释和厌氧琼脂稀释方法。标准化测试方法的修改包括添加 10％人血清和将培养基 pH 值调节至 5、6 和 8。协同作用通过棋盘法和时间杀伤研究进行评估。在 4x、8x 和 16xMIC 下测定耐药突变率。针对革兰氏阳性病原体，夫西地酸 MIC 值范围为 0.06 至 32μg/ml，对金黄色葡萄球菌、棒状杆菌属和微球菌属的效力最强（MIC 结果分别为 0.25、<或=0.12 和<或=0.5μg/ml）。肠球菌和链球菌的敏感性较低（MIC 范围分别为 2-8 和 16-32μg/ml）。夫西地酸对革兰氏阴性物种的活性更有限（所有 MIC 值均>或=2μg/ml），但埃希氏菌属 Brevis、卡他莫拉菌和脑膜炎奈瑟菌除外。在肉汤中添加 10％血清时，夫西地酸 MIC 值增加了 4 倍。将培养基 pH 值降低至 5.0 至 6.0 可消除蛋白质结合作用。在所测试的 8 种抗菌组合中，当与夫西地酸联合使用时，庆大霉素和利福平增强了其活性（无拮抗作用）。当与利福平联合使用时，夫西地酸的体外活性得到最大改善。单步突变率范围从 4xMIC 的 1.2x10(-6)到 16xMIC 的 9.8x10(-8)。总之，这些针对当代菌株测试的夫西地酸的体外结果证实了一种持续存在的抗菌谱，特别是针对葡萄球菌和其他一些革兰氏阳性物种。
