来氟米特对氟康唑体外抗耐药白色念珠菌增效作用研究

目的：研究来氟米特与氟康唑在体外合用对耐药白色念珠菌的抗真菌效果。方法：采用棋盘式微量稀释法测定来氟米特联合氟康唑对15株临床耐药白色念珠菌的最小抑菌浓度MIC₈₀。时间-杀菌曲线验证两药联用对耐药白色念珠菌生长的抑制作用。结果：来氟米特单药对实验所用白色念珠菌均无抗菌活性（MIC₈₀>320μg·mL^-1）。来氟米特联合氟康唑可产生协同抗菌作用，协同指数（FICI）<0.25。用药24h后，时间-杀菌曲线上联合用药组比单用氟康唑组平均降低了3.9log₁₀CFU/mL，证实两药具有协同抑菌作用。结论：来氟米特与氟康唑在体外对耐药白色念珠菌具有良好的协同抗真菌活性。

Synergistic effect of leflunomide with fluconazole against fluconazole-resistant Candida albicans

OBJECTIVE To investigate the antifungal effect of lefluomide with fluconazole against fluconazole-resistant Candida albicans in vitro.METHODS The minimal inhibitory concentrations (MIC₈₀) of 15 fluconazole-resistant Candida albican strains by leflunomide. The minimum inhibitory concentration MIC₈₀ of leflunomide combined with fluconazole against 15 clinically resistant Candida albicans strains was determined by checkerboard microdilution method. The time-kill curve verified the inhibitory effect of the combination of the two drugs on the growth of resistant Candida albican.RESULTS There was no antimicrobial activity of leflunomide alone against the Candida albican strains (MIC₈₀>320 μg·mL^-1). The combination of leflunomide with fluconazole had a significant synergistic effect on the fluconazole-resistant Candida albicans (FICI<0.25). On the time-kill curve, combination therapy yielded a 3.9 log₁₀CFU/mL decrease compared with fluconazole alone after 24h of incubation. It was confirmed that the two drugs had synergistic antimicrobial activity.CONCLUSION Leflunomide and fluconazole have good synergistic antifungal activity against drug-resistant Candida albicans in vitro.