甲硝唑联合利奈唑胺、非达霉素和万古霉素对艰难梭菌体外抗菌活性研究

In vitro antibacterial activity of metronidazole combined with linezolid,fidaxomycin and vancomycin against Clostridium difficile

目的本研究旨在探讨甲硝唑与3种抗生素(利奈唑胺、非达霉素、万古霉素)分别联用对临床分离的艰难梭菌的体外抗菌活性,为临床联合用药提供实验依据。方法将甲硝唑与其它3种抗菌药在体外单独以及联合应用作用于32株艰难梭菌菌株,采用琼脂二倍稀释法,测定最低抑菌浓度(MIC)、计算部分抑菌浓度(FIC)指数,绘制杀菌曲线。评价甲硝唑与其它3种抗菌药物分别联合应用的体外抗茵活性。结果利奈唑胺、非达霉素、万古霉素分别与甲硝唑在体外联合应用后,利奈唑胺和非达霉素联合用药后MIC值均比单独应用时下降,联合药敏指数均≤2;联合应用对艰难梭菌杀茵速度加快,杀菌作用增强。万古霉素联合甲硝唑MIC值无明显改变。结论利奈唑胺、非达霉素分别与甲硝唑在体外联合均具有协同抗菌作用,能降低对艰难梭菌的MIC,而万古霉素联合甲硝唑MIC无明显改变。

Objective To investigate the antibacterial activity in vitro of metronidazole combined with three antibiotics（linezolid,fidaxomycin and vancomycin）in clinical isolates of Clostridium difficile,and to provide experimental basis for combination therapy. Methods The metronidazole and other three kinds of anti-inflammatory drugs in vitro and in combination were applied to 32 Clostridium difficile strains,by agar double dilution method,MIC was calculated to calculate the fractional antibacterial concentration（FIC）index,draw bactericidal curve. Anti-inflammatory activity in vitro of metronidazole and other three kinds of antibacterial drugs were evaluated. Results Linezolid,fidagamicin,vancomycin combined with metronidazole respectively in vitro,MIC values were lower with the combination of linezolid and fidaxomycin than alone,the combined susceptibility index were all less than 2;Clostridium difficile killed speed with combined application was faster,the effect increased. MIC value of vancomycin combined with metronidazole was no significant changed. Conclusion Linezolid and fidaxomycin combined with metronidazole in vitro had a synergistic antibacterial effect,which could reduce the MIC against Clostridium difficile,but MIC was no significant change in the vancomycin combined with metronidazole.