两种钙调磷酸酶抑制剂联合常用抗真菌药物对马尔尼菲青霉酵母相体外药敏的研究

THE STUDY OF THE DURG SENSITIVITY OF TWO KINDS OF CLACINEURIN INHIBITORS COMBINED WITH COMMON ANTIFUNGAL DRUG PENICILLIUM MARNEFFEI ON THE YEAST PHASE

目的:探讨两种钙调磷酸酶抑制剂联合常用抗真菌药物,对20株马尔尼菲青霉(PM)酵母相体外药敏的作用。方法:参照美国临床和实验室标准协会(CLSI)M27-A3方案并做适当修改,采用棋盘格微量稀释法对20株PM酵母相进行钙调磷酸酶抑制剂环孢素A(CsA)、他克莫司(FK506)与5种常用抗真菌药物联合的体外药敏实验。结果:CsA与两性霉素B(AmB)、伊曲康唑(ITC)、氟康唑(FLC)联合时,各药的最低抑菌浓度(MIC)值均比单用时明显降低(均P<0.05)。CsA与AmB、ITC、FLC联合,分别有17株(85%)、13株(65%)、6株(30%)的菌株显示协同作用;而CsA与米卡芬净(MCFG)、卡泊芬净(CPFG)联合所有菌株均表现为无关联作用。FK506与以上5种抗真菌药联合时,各药物的MIC值较单用时无明显变化,联合时呈无关联作用。在所有受试PM酵母相中,CsA及FK506与以上5种抗真菌药物联合均未出现拮抗作用。结论:体外药敏研究显示,CsA与FK506在体外联合药敏中作用不同,CsA可增强AmB、ITC、FLC对PM酵母相的抗真菌活性;但FK506则无此作用。

Objective：To evaluate the in vitro interaction effects of two kinds of calcineurin inhibitors combined with antifungal agents against on the pathogenic yeast form of P. Marneffei（PM）. Methods： according to American clinical and Laboratory Standards Institute （CLSI） M27-A3 scheme , the scheme was made appropriate modifications. Then 20 strains of PM yeast phase of calcineurin inhibitors cyclosporine was performed durg sensitivity tests with checkerboard microdilution method bt （CsA）, tacrolimus （FK506） combined with 5 kinds of commonly used antifungal drugs in vitro. Results： the MIC effectof CsA with amphotericin B （AmB）, or itraconazole （ITC） or fluconazole （FLC） were significantly lower than the single use （P 〈 0.05）. When CsA respectively combined with AmB, ITC, FLC, the synerigistic rate of them respeci- tively were 85%, 65%, and 30^; But there was no role on yests when the CsA respectively combined with micafungin （MCFG）,or caspofungin （CPFG）. Meanwhile, no synergism was observed in the combinations of tacrolimus（FK506） with other five antifungal agents. No antagonism was observed for any of the anti- fungal combinations assayed in the study. Conclusion. in vitro susceptibility studies show, CsA and FK506 in different in vitro drug sensitivity in CsA, ITC, FLC, AmB can enhance the antibacterial activity of the yeast phase of PM. But FK506 didn＇t have such effects. Conclusion;The research showed that CsA could en- hance the activity of AmB,ITC,FLC against the yeast form of PM. FK506 did not exert synergistic activity with any of the five antifungal agents used in this study, further researches are required to the mechanism.