环孢素A联合抗真菌药物体外抗茄病镰刀菌效果研究

In vitro interactions between antifungals and Cyclosporin A against Fusarium solani

目的:研究免疫抑制剂环孢素A联合使用抗真菌药物对镰刀菌体外抗真菌药物敏感性的影响。方法:采用美国临床实验室标准化委员会(CLSI)M27-Ed4及M38-A3方法测定伏立康唑(voriconazole)、那他霉素(NAT)和两性霉素B(Amphotericin B)及氟康唑(FLU)对22株镰刀菌的最低抑菌浓度(MIC),棋盘法测定四种抗真菌药物单独及联合环孢素A使用抗真菌作用。结果:那他霉素、伏立康唑、两性霉素B和氟康唑对镰刀菌(22株)MIC范围分别是2~8、1~8、1~8和8~512μg/mL。体外联合用药时,环孢素A与氟康唑对64%菌株(14/22)有协同效应,与两性霉素B对41%菌株(9/22)有协同效应,对所有菌株无拮抗效应。联合使用环孢素A后,镰刀菌对两性霉素B药物敏感性由4.5%提升至68.2%(P<0.001)。结论:镰刀菌在体外对那他霉素敏感,对伏立康唑部分敏感。与环孢素A联合应用时,可与氟康唑及两性霉素B产生协同效应,并显著提高镰刀菌对两性霉素B药物敏感性。

AIM:To investigate the in vitro interaction between antifungals and tacrolimus acting alone or in combination against Fusarium solani.METHODS:According to Clinical and Laboratory Standards Institute(CLSI)M27-Ed4 and M38-A3,22 strains of Fusarium solani were used to perform drug sensitivity tests with chessboard microdilution method by cyclosporin A combined with 4 kinds of antifungal drugs in vitro.RESULTS:The MIC ranges of natamycin,voriconazole,amphotericin B and fluconazole against 22 strains of Fusarium solani were 2-8,1-8,1-8 and 8-512μg/mL respectively.When combined with tacrolimus in vitro,the synergistic effects of fluconazole and Amphotericin B were observed in 64%and 41%strains respectively.There were no antagonistic effects observed in all combined drug tests.With the combination,the sensitivity of Fusarium to amphotericin B was significantly increased from 4.5%to 68.2%(P<0.001).CONCLUSION:Fusarium solani is sensitive to natamycin in vitro and is partially sensitive to voriconazole.When combined with cyclosporine A,it can produce synergistic effects with fluconazole and amphotericin B,and significantly increase the sensitivity of Fusarium solani to amphotericin B drugs.