【摘要】 目的 :评价新的唑类抗真菌药物SCH 56592体内外抗临床分离的新型隐球菌活性。方法 :依照美国国家临床试验标准化委员会推荐的M2 7 A方案的微量稀释法测定 2 6株新型隐球菌对SCH 56592及氟康唑、伊曲康唑和两性霉素B的MICs。比较SCH 56592与氟康唑治疗免疫功能抑制的鼠肺隐球菌病的疗效。结果 :SCH 56592对于临床分离的 2 6株新型隐球菌的体外抗菌活性是氟康唑的 1 6～ 64倍 ,对氟康唑耐药的新型隐球菌的MIC(0 .0 5μg·mL- 1 )是伊曲康唑MIC(2 μg·mL- 1 )的 1 / 4 0倍。SCH 56592不仅明显降低氟康唑敏感新型隐球菌株感染小鼠的肺内菌数 (P <0 .0 5) [SCH 56592组为 (2 .90± 1 .90 )× 1 0 7CFU·mL- 1 ,对照组为 (46 .60± 2 9.58)×1 0 7CFU·mL- 1 ] ;而且明显降低氟康唑耐药的新型隐球菌株感染的小鼠肺内菌数 [SCH 56592组为 (5 .30± 2 .36)×1 0 7CFU·mL- 1 ,对照组为 (1 97.70± 1 0 .37)× 1 0 7CFU·mL- 1 ,氟康唑治疗组为 (1 90 .60± 97.63)× 1 0 7CFU·mL- 1 ,与后 2组比较 ,均为P <0 .0 5]。肺隐球菌感染的小鼠经SCH 56592治疗后生存时间延长 ,生存率提高。结论 :SCH 56592具有良好的体内、体外抗临床分离的新型隐球菌活性 ;对于氟康唑耐药的新型球菌具有极好的抗真菌活性。更多还原

【Abstract】 Objective:To investigate the in vitro and in vivo activity of SCH 56592, a new triazole antifungal agent, against clinical isolates of Cryptococcus neoformans .Methods:A broth microdilution method performed in accordance with the National Committee for Clinical Laboratory Standards (NCCLS) guidelines was used to determine the MICs of SCH 56592,fluconazole(FLCZ),itraconazole(ITCZ) and amphotericin B(AmB) for 26 strains of Cryptococcus neoformans . In vivo effects of SCH 56592 was compared with FLCZ for the treatment of pulmonary Cryptococcosis in immunosuppressed mice.Results:MICs of SCH 56592 was 16～64 fold more active than FLCZ against these Cryptococcus neoformans isolates, and was 40 fold more active than ITCZ against FLCZ resistant Cryptococcus neoformans isolate.For FLCZ susceptible Cryptococcus neoformans isolate infected mice of pulmonary Cyptococcosis ,the fungal burden of the lung of mice treated with SCH 56592 was significantly reduced[(2.90±1.90)×10 7CFU·mL -1 ],as compared with control [(46.60±29.58)×10 7CFU·mL -1 , P < 0.05].For FLCZ resistant Cryptococcus neoformans isolate infected mice of pulmonary Crypcococcosis ,the fungal burden of the lung of mice treated with SCH 56592 was also significantly reduced [(5.30± 2.36)×10 7CFU·mL -1 ], as compared with control[(197.70±10.37)×10 7CFU·mL -1 , P < 0.05] and FLCZ [(190.60±97.63)×10 7CFU·mL -1 ( P <0.05)]. The survival time of mice infected with pulmonary Cyptococcosis was prolonged after treatment with SCH 56592.Conclusion:SCH 56592 is one of more activities against Cryptococcus neoformans and FLCZ resistant Cryptococcus neoformans from isolated clinical in vitro and in vivo .更多还原