伏立康唑、氟康唑和两性霉素B体内抗克柔念珠菌活性的比较研究

Comparative Studies of the Antifungal Activities of Voriconazole,Fluconazole and Amphotericin B Against Candida Krusei in Vivo

目的比较伏立康唑、氟康唑和两性霉素B在体内对克柔念珠菌的抗真菌活性。方法在克柔念珠菌深部感染的免疫抑制豚鼠模型上,对感染豚鼠分组给予口服伏立康唑10mg/kg,2次/d;伏立康唑5mg/kg,2次/d;氟康唑20mg/kg,2次/d;两性霉素B1mg/kg隔日1次腹腔注射;安慰剂对照组给予生理盐水0.5ml,2次/d口服。均连续7天。观察比较各组的死亡率及脏器组织载菌量。结果安慰剂对照组豚鼠的所有受检脏器都受到了严重的感染。5个处理组中,伏立康唑10mg组的组织载菌量与死亡率(0%)均最低;与对照组相比,该方案使念珠菌在肺、肝、肾、脑四种脏器中的组织载菌量都减少了约99%(P<0.01)。伏立康唑5mg组的组织载菌量和豚鼠死亡率均与安慰剂对照组相近,无显著性差异。氟康唑组的组织载菌量与对照组相近,其死亡率(40%)仅略低于对照组,两组间无显著性差异(P>0.05)。伏立康唑10mg组与两性霉素B组相比,在组织载菌量和死亡率方面均较为接近,较之安慰剂对照组均有显著差异(P<0.01)。结论伏立康唑在免疫抑制豚鼠体内能有效地抑制感染脏器中克柔念珠菌的生长,其作用明显优于氟康唑,与两性霉素B作用相近,但两性霉素B常有严重的不良反应。伏立康唑在体内可能以剂量依赖的形式显示其抗真菌活性。

Objective To compare the antifungal activities of voriconazole against Candida krusei with fluconazole and amphotericin B in vivo. Methods The immunocompromising guinea pigs models were deeply infected with Candida krusei, which in different groups were treated by voriconazole 10 mg/kg orally twice daily, voriconazole 5 mg/kg orally twice daily, fluconazole 20 mg/kg orally twice daily and amphotericin B 1 mg/kg i. p. on alternate days,control group was treated by 0.9% NS 0.5 ml orally twice daily, respectively for 7 days. The mortality and tissue burden of each group were observed and compared. Results All of the tested organs in control groups were seriously infected. Among all the five groups, the tissue burden and the cumulative mortality （0%） of voriconazole 10 mg group were the lowest. Compared with that in the control group, the application of voriconazole （10mg/kg orally twice daily） reduced the tissue burdens in four organs （lung,liver,kidney and brain） as much as 100-fold （P 〈 0.01 ）. The tissue burdens and mortalities of voriconazole 5 mg group were similar to that of control group ,without significant difference between two groups. The tissue burden of fluconazole group was similar to that of control group, and mortality of fluconazole group （40%） was just a little lower than that of control group,without significant difference between two groups （ P 〉 0.05 ）. Comparing voriconazole 10 mg group with amphotericin B group, in whole sense, the tissue burdens and mortalities of both group were similar,and were significantly different to the control group （ P 〈 0.01 ）. Conclusion Voroconazole could effectively inhibit the growth of Candida krusei in the infected organs of the immunocompromising guinea pigs. For treating infections caused by Candida krusei ,the efficacy of voriconazole was much better than that of fluconazole ,similar to that of amphotericin B. Considering the common and serious adverse events of amphotericin B, voriconazole may be more predominant when you choice the drugs in clinic. Voriconazole revealed its antifungal activity by a dose-dependent pattern in vivo.