新的唑类抗真菌药BMS-207147体内和体外的抗新型隐球菌活性

In vitro and in vivo activities of the new triazole BMS-207147 against Cryptococus neoformans

BMS 2 0 71 4 7是一个新的口服唑类抗真菌药物。本研究中 ,我们采用微量稀释法测定了BMS 2 0 71 4 7对于 2 6株临床分离的新型隐球菌体外敏感性 (MICs) ,且通过用BMS 2 0 71 4 7治疗鼠肺隐球菌病了解体内抗隐球菌疗效 ,并与氟康唑进行了比较。对于 2 6株新型隐球菌的MIC90 ,BMS 2 0 71 4 7为 0 0 62 5mg/L ,氟康唑是它的 32倍 ;伊曲康唑是它的 4倍 ;伏立康唑 (voriconazole)是它的 2倍。而且对于氟康唑耐药的新型隐球菌的MIC ,伊曲康唑和伏立康唑是BMS 2 0 71 4 7的 4倍。在肺隐球菌病的鼠模型实验中 ,BMS 2 0 71 4 7不仅能显著地降低由氟康唑敏感菌株感染的肺内菌数和脑内菌数 (CFU/ml) ,(与对照组比较P <0 0 5) ;而且能显著地降低氟康唑耐药新型隐球菌感染的肺内菌数和脑内菌数 (CFU/ml) ,与氟康唑治疗组相比较P <0 0 5。结论 :BMS 2 0 71 4 7具有高效的体内。

According to the approved standard M27 A method of National Committee for Clinical Laboratory Standard (NCCLS), the in vitro MICs of BMS 207147 against 26 clinical isolates of Cryptococcus neoformans were measured. The therapeutic effects of oral BMS 207147 on mice affected with pulmonary cryptococcosis were investigated and compared with that of fluconazole. The MIC 90 of BMS 207147 against clinical isolates of Cryptococcus neoformans was 0 0625 μg/ml, while for fluconazole,itracoazole and voriconazole, the MIC 90s were 2, 0 25 and 0 125μg/ml respectively. In the case of fluconazole resistant Cryptococcus neoformans , the MICs of itraconazole and voriconazole were four fold higher than BMS 207147. In mice affected with fluconazole susceptible Cryptococcus neoformans , pulmonary crytococcosis, the numbers of CFU in lung and brain of the animals treated with BMS 207147 were reduced significantly than the control, ( P <0.05); and the same results were seen in the case of animals affected with the fluconazole resistant Cryptococcus neoformans ( P <0.05). These results suggested that BMS 207147 was a potent in vitro and in vivo antifungal agent against Cryptococcus neoformans .