Correa A L, Velez G, Albert M, Luther M, Rinaldi M G, Graybill J R
Department of Medicine University of Texas Health Science Center, San Antonio, USA.
J Med Vet Mycol. 1995 Nov-Dec;33(6):367-74. doi: 10.1080/02681219580000721.
Cryptococcal meningitis is a common infection in patients with AIDS. Using a murine cryptococcosis model, we compared treatment with a new triazole, D0870, and fluconazole. Groups of ICR (Institute for Cancer Research) mice were infected intracerebrally with eight different isolates of Cryptococcus neoformans variety neoformans with different in vitro susceptibilities to fluconazole. For survival studies mice were challenged with two to four times LD(50) or six to nine times LD(50). Treatment was given for 10 days. Mice were observed through to day 30. To assess the effect of treatment on fungal tissue burden, mice received a three to five times LD(50) inoculum and treatment for 10 days. They were sacrificed on day 12 and serial dilutions of brain homogenates were cultured. Fluconazole prolonged survival primarily in isolates which were susceptible in vitro. D0870 prolonged survival in all isolates except one, which was also resistant in vitro to D0870 and fluconazole. Both drugs reduced colony counts of all isolates. D0870 warrants further development for use in cryptococcosis, and appears effective for isolates relatively resistant to fluconazole. There is a relative correlation of in vivo and in vitro susceptibility to D0870 as well as fluconazole.
隐球菌性脑膜炎是艾滋病患者常见的感染。我们使用小鼠隐球菌病模型，比较了新型三唑类药物D0870和氟康唑的治疗效果。将几组ICR（癌症研究学会）小鼠脑内接种8种对氟康唑体外敏感性不同的新型隐球菌新生变种分离株。在生存研究中，用2至4倍半数致死量（LD50）或6至9倍LD50对小鼠进行攻击。治疗持续10天。观察小鼠直至第30天。为评估治疗对真菌组织负荷的影响，给小鼠接种3至5倍LD50的菌量并治疗10天。在第12天处死小鼠，对脑匀浆进行系列稀释后培养。氟康唑主要延长了体外敏感分离株小鼠的生存期。D0870延长了除一株以外所有分离株小鼠的生存期，该株在体外对D0870和氟康唑均耐药。两种药物均降低了所有分离株的菌落计数。D0870值得进一步开发用于隐球菌病治疗，且对相对耐氟康唑的分离株似乎有效。对D0870以及氟康唑，体内和体外敏感性存在相对相关性。
