低浓度他克莫司与抗真菌药物联合的体外抗真菌效应

In vitro antifungal activity of tacrolimus combined with antifungals against Candida spp. and dermatophytes

目的测定他克莫司(FK-5066)与抗真菌药物对浅部致病真菌的联合效应。方法参考CLSI的M27-A3和M38-A2方案分别测定酮康唑对念珠菌、特比萘芬对皮肤癣菌的最低抑菌浓度(MIC);利用棋盘法,测定他克莫司与酮康唑或特比萘芬的联合抗真菌效果。结果酮康唑单独对念珠菌MIC50和MIC90分别为:4μg/m L和8μg/m L;与他克莫司联合应用时,对53.3%的菌株有联合效应(n=15),对其余菌株无协同效应。特比萘芬单独对皮肤癣菌MIC50和MIC90分别为:0.06μg/m L和0.125μg/m L;与他克莫司联合应用时,对46.7%菌株(n=15)有协同效应,对其余菌株表现为无关。结论低浓度他克莫司在体外与抗真菌药物联合应用时,能够降低药物对部分菌株的MIC,未发现拮抗效应。

Objectives To investigate the in vitro antifungal susceptibility of FK-506 combined with antifungals to Candida spp.and dermatophytes. Methods The minimal inhibitory concentrations （MICs） of Candida spp.against ketoconazole and dermatophytes against terbinafine were assayed using CLSI M27-A3 and M38-A2 microdilution method,respectively.By using broth microdilution checkerboard technique system,we evaluated the combined antifungal activity of tacrolimus with ketoconazole or terbinafine against Candida spp.and dermatophytes,respectively. Results The MIC50 and MIC90 of ketoconazole against Candida spp.were 4 μg/mL and 8 μg/mL,respectively.The MIC50 and MIC90 of terbinafine against dermatophytes were 0.06 μg/mL and 0.125 μg/mL,respectively.The result showed that the combination of tacrolimus and Ketoconazole or Terbinafine had synergistic inhibitory activity against Candida spp.（53.5%,n=15） and dermatophytes （46.7%,n=15）. Conclusion The MICs of antifungals can be reduced partly when combined with low concentration of FK-506 against Candida spp.and dermatophytes,and no antagonism was found.