粉防己碱对酮康唑抗近平滑念珠菌复合体的体外增效活性研究
In vitro synergistic effect of tetrandrine on ketoconazole against Candida parapsilosis complex
摘要目的 探讨粉防己碱在体外对酮康唑抗近平滑念珠菌复合体有无增效作用.方法 参照美国临床和实验室标准协会(CLSI)推荐的M27-A3方案,采用棋盘式微量稀释法测定酮康唑单独及联合粉防己碱抗21株近平滑念珠菌复合体临床株抗真菌活性,结合部分抑制浓度指数(FICI)对结果进行评价;以甲基四氮盐(XTT)法分别测定不同时间点药物作用的效果,绘制时间杀菌曲线,动态观察药物体外抗近平滑念珠菌复合体活性.结果 粉防己碱与酮康唑单独作用于21株近平滑念珠菌复合体菌株的最低抑菌浓度分别是32~64 mg/L和0.031 25~2 mg/L,两药联合时最低抑菌浓度分别降至2 ~8 mg/L和0.008~0.25 mg/L,FICI值为0.09 ~ 0.5;时间杀菌曲线表明,与酮康唑单用组和粉防己碱单用组相比,酮康唑联合粉防己碱组真菌生长延迟明显.结论 粉防己碱在体外对酮康唑抗近平滑念珠菌复合体有明显的增效作用.
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abstractsObjective To evaluate the in vitro synergistic effect of tetrandrine on ketoconazole against Candida parapsilosis complex.Methods According to the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines,the microdilution checkerboard method was used to evaluate in vitro antifungal activities of ketoconazole alone and in combination with tetrandrine against 21 clinical isolates of Candida parapsilosis complex based on the fractional inhibitory concentration index (FICI).Antifungal effects of the above drugs at different time points were evaluated by the XTT assay,and then time-killing curves were drawn and assessed to investigate the in vitro dynamic antifungal activity.Results The minimum inhibitory concentrations (MICs) of tetrandrine and ketoconazole alone against 21 clinical isolates of Candida parapsilosis complex were 32-64 mg/L and 0.031 25-2 mg/L,respectively.When ketoconazole was combined with tetrandrine,MICs of tetrandrine and ketoconazole were reduced to 2-8 mg/L and 0.008-0.25 mg/L respectively,and the FICI ranged from 0.09 to 0.5.The time-killing curves revealed that the fungal growth was delayed obviously in the combination group compared with the ketoconazole alone group and tetrandrine alone group.Conclusion Tetrandrine has obvious synergistic effects on ketoconazole against Candida parapsilosis complex in vitro.
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