伏立康唑与布地奈德联用抗白色念珠菌的作用研究

Study on the effect of voriconazole and budesonide against Candida albicans

目的研究伏立康唑与布地奈德联用的体内、外抗白色念珠菌活性。方法采用微量稀释法测定两药联用的体外抗真菌作用,并以部分抑菌浓度指数模型和生长差异百分率模型共同地评价两药联合抗真菌作用效果。使用大蜡螟作为感染模型,通过测定感染后大蜡螟的生存率、载菌量和组织病理学改变综合评价两药联用在体内的疗效。结果与对照组和药物单用组相比,两药联用对耐药白色念珠菌有明显的体外协同作用,但对敏感白色念珠菌无体外协同作用。与对照组和药物单用组相比,两药联用可显著提高感染耐药白色念珠菌的大蜡螟的生存率(P<0.05)、降低载菌量(P<0.05)并减少组织破坏,但两药联用对感染敏感白色念珠菌的的大蜡螟的生存率、载菌量、组织病理学均无显著影响。结论两药联用对耐药白色念珠菌有显著的体内、外协同作用。

Objective To observe the antifungal effects of voriconazole(VRC) combined with budesonide (BUD) against Candida albicans in vivo and in vitro. Methods The in vitro antifungal effects of voriconazole in combination with budesonide against Candida albicans were determined by a broth microdilution method.Fractional inhibitory concentration index (FICI) model and percentage of growth difference (△ E ) model were used to interpret the antifungal effects in vitro.Using Galleria mellonella as the infection model,the survival rates,fungal burden and histopathology of infected larvae were used to determine the in vivo antifungal effects of voriconazole in combination with budesonide. Results Compared to control and drug alone groups,the combination of voriconazole and budesonide had effects against resistant Candida albicans in vitro ,while no synergetic effects were observed for susceptible Candida albicans .Furthermore,the combination of voriconazole and budesonide significantly improved the survival rates ( P <0.05),reduce fungal burden ( P <0.05) and reduce tissue damage of Galleria mellonella infected with resistant Candida albicans, while no significant effect was found in Galleria mellonella infected with susceptible Candida albicans . Conclusion Voriconazole in combination with budesonide has significantly synergetic effects against resistant Candida albicans in vivo and in vitro .