夫西地酸对葡萄球菌体外抗菌作用研究

In vitro antibacterial effects of fusidic acid against Staphylococus spp.

目的评价夫西地酸对临床分离葡萄球菌的体外抗菌作用及影响因素。方法以琼脂二倍稀释法测定抗菌药物最低抑菌浓度,棋盘法测定联合抗菌作用并以杀菌曲线测定夫西地酸杀菌特征。结果对临床分离的359株葡萄球菌MIC测定结果显示夫西地酸对苯唑西林耐药葡萄球菌MIC50及MIC90值分别为0.25～1及1～8mg/L;对苯唑西林敏感葡萄球菌MIC50及MIC90值分别为0.25～0.5及0.5～1mg/L;抗菌活性与万古霉素、替考拉宁相似或稍强,93.16%的葡萄球菌对夫西地酸敏感,耐药菌主要为凝固酶阴性葡萄球菌;未发现万古霉素耐药葡萄球菌,但3.62%细菌对替考拉宁耐药。夫西地酸与亚胺培南、帕尼培南和美罗培南3种碳青霉烯类抗生素联用具有协同或相加作用,其中协同作用分别为87.5%、70.83%和43.75%,无拮抗作用;糖肽类药物与碳青霉烯类药物联用以协同与相加效果为主。夫西地酸对苯唑西林耐药和敏感葡萄球菌杀菌作用迅速,但杀菌作用在较高浓度时并没有进一步提高杀菌速度,提示该产品可能属于非浓度依赖性抗菌药物。结论夫西地酸对各种葡萄球菌,包括耐苯唑西林葡萄球菌,具有良好抗菌作用,其抗菌作用可能属于非浓度依赖性;夫西地酸与碳青酶烯类抗生素联用具有明显协同抗菌效果。

Objective To investigate in vitro antibacterial effects of fusidic acid against Staphylococcus spp. Methods The MICs of antibacterial agents were determined by the standard two-fold agar dilution method and combination effects of antibacterial agents were tested by checker board method and time-kill curves were conducted by colony form unit （CFU） count method. Results Fusidic acid had potent antibacterial activity against 359 clinical strains of oxacillin-susceptible and resistant Staphylococcus spp., the MIC50s and MIC90s of fusidic acid against oxacillin-resistant Staphylococcus spp. were 0.25 - 1mg/L and 1 - 8mg/L; the MIC50s and MIC90s of fusidic acid against oxacillin-susceptible Staphylococcusspp were 0.25 -0.5mg/L and 0.5 - 1 mg/L, respectively. The antibacterial activity of fusidic acid was comparable or superior to those of vancomycin and teicoplanin. 93.16% strains of Staphylococcus spp. were susceptible to fusidic acid and majority of the resistant strains were coagulase-negative isolates. No vancomycin-resistant Staphylococcus spp. was detected, but 3.62% isolates were resistant to teicoplanin. The combination effects of fusidic acid plus carbapenems （including imipenem, panipenem and meropenem） were synergism and addition, in which 87.5%, 70.83% and 43.75% synergistic effect were detected, respectively. The combination between glycopeptides and carbapenems also demonstrated synergistic effect. The bacterial killing curves showed that fusidic acid sustained bactericidal effect against both oxacillin-susceptible and resistant Staphylococcus spp., which was faster than those of vancomycin and teicoplanin. The time-killing curves conducted in different drug concentrations indicated that fusidic acid could be a non-concentration dependent antibacterial agent. Conclusions Fusidic acid is an effective antibacterial agent against oxacillin-susceptible and -resistant Staphylococcus spp., the combination of fusidic acid with earbapenems have synergistic effect and fusidic acid could be a non-concentration dependent antibacterial agents. All these characters make fusidic acid a meaningful agent in clinical practice for the treatment of staphylococcal infections.