摘要
目的探讨水飞蓟宾及同分异构体的体外抗菌谱及水飞蓟宾与临床常用抗生素的联合抑菌效应。方法用微量肉汤稀释法测定水飞蓟宾及同分异构体对临床感染常见细菌的6种标准菌株和6种临床分离菌株(74株)的最低抑菌浓度(MIC)。用平板菌落计数法测定不同质量浓度水飞蓟宾对6种标准菌株的生长抑制曲线。用棋盘微量肉汤稀释法进行水飞蓟宾与临床常用抗生素的联合药敏试验,计算联合抑菌指数(FIC),判定水飞蓟宾与抗生素的联合抑菌效应。结果水飞蓟宾对表皮葡萄球菌、金黄色葡萄球菌、粪肠球菌和屎肠球菌标准菌株的MIC为50~400μg/m L,对大肠埃希菌和铜绿假单胞菌标准菌株的MIC均>400μg/m L;对表皮葡萄葡萄球菌临床分离菌株的MIC分别为100、200、400、>400μg/m L,对金黄色葡萄球菌、粪肠球菌和屎肠球菌临床分离菌株的MIC分别为400、>400μg/m L;对大肠埃希菌和铜绿假单胞菌临床分离菌株的MIC均>400μg/m L。水飞蓟宾其他同分异构体对6种标准菌株的MIC为≥400μg/m L。水飞蓟宾对表皮葡萄球菌、金黄色葡萄球菌、粪肠球菌和屎肠球菌标准菌株的生长曲线都有明显抑制作用,抑制效果随药物质量浓度增加而增加,对大肠埃希菌和铜绿假单胞菌标准菌株的生长曲线无影响。水飞蓟宾与青霉素/红霉素联用对革兰阳性试验菌的FIC以0.52或1 Objective To investigate the in vitro antibacterial spectrum of silibinin and its isomers and the combined antibacterial effect of silibinin and commonly-used clinical antibiotics. Methods Micro-broth dilution method was used to determine the minimum inhibitory concentration(MIC) of silibinin and its isomers against six standard strains and six clinical isolates(74 strains) of common bacteria infections. Plate count method was used to measure the growth inhibition curves of different concentrations of silibinin against six standard strains. Checkerboard micro-broth dilution method was used to carry out the combined susceptibility test of silibinin and clinical antibiotics. The fractional inhibitory concentration(FIC) was calculated to determine the combined antibacterial effect of silibinin and antibiotics. Results The MICs of silibinin against standard strains of Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium were between 50 μg/m L and 400 μg/m L, and those of silibinin for standard strains of Escherichia coli and Pseudomonas aeruginosa were both greater than 400 μg/m L. The MICs of silibinin for clinical strains, Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium were all within the range of 100 μg/m L to 400 μg/m L, and MICs of silibinin against clinical strains of Escherichia coli and Pseudomonas aeruginosa were greater than 400 μg/m L. The MICs of other isomers of silibinin against six standard strains were greater than or equal to 400 μg/m L. Silibinin had a significant inhibitory effect on the growth curve of standard strains of Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium, which increased with increasing drug concentration, and it had no effect on that of Escherichia coli and Pseudomonas aeruginosa. The FIC of silibinin combined with penicillin/erythromycin for gram-positive test bacteria was in the range of 0.5 < FIC ≤ 1 and 1 < FIC ≤ 2, and FIC of silibinin combined with ciprofloxacin or gentamicin for gram-negative test bacteria was in the range of FIC > 2 or 1 < FIC ≤ 2. Conclusion Silibinin has a notable antibacterial activity to gram-positive bacteria with the best inhibitory effect on Staphylococcus epidermidis. The antibacterial activities of silibinin is higher than those of other isomers. The combined antibacterial effect of silibinin and penicillin/erythromycin is mainly additive and irrelevant, while that of silibinin and ciprofloxacin or gentamicin is mainly antagonistic or irrelevant.
引文
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