Hossain M A, Mukherjee P K, Reyes G, Long L, Ghannoum M A
Center for Medical Mycology, Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, OH 44106-5028, USA.
J Chemother. 2002 Aug;14(4):351-60. doi: 10.1179/joc.2002.14.4.351.
In this study we developed a highly reproducible intracranial murine model of cryptococcosis. Mice (Balb/c, 5-7 weeks old) were challenged intracranially and treated with intermediate (30 mg/kg) or high (90 mg/kg) dose fluconazole, and amphotericin B (0.75 mg/kg), administered singly or in combination with flucytosine (100 mg/kg). Survival and brain CFU analyses were performed. Effect of fluconazole prophylaxis was also determined. Our data show that the developed model mimics clinical signs of cryptococcal meningitis. In single treatment, fluconazole (30 mg/kg) was more efficacious than amphotericin B or flucytosine (P < 0.0001). Combination treatment led to significantly increased anticryptococcal activity, which was highest for high dose fluconazole + flucytosine (P < 0.0001). However, no significant difference was observed between high dose fluconazole treatment with and without flucytosine (P >0.05). Fluconazole prophylaxis led to a significant decrease in brain CFU. In conclusion, high dose fluconazole administered post-infection, or as prophylaxis, may be highly efficacious in the treatment and prevention of meningoencephalitis.
在本研究中，我们建立了一种高度可重复的颅内隐球菌病小鼠模型。对小鼠（5 - 7周龄的Balb/c小鼠）进行颅内接种，并分别用中等剂量（30 mg/kg）或高剂量（90 mg/kg）氟康唑、两性霉素B（0.75 mg/kg）进行治疗，这些药物单独使用或与氟胞嘧啶（100 mg/kg）联合使用。进行了生存分析和脑内菌落形成单位（CFU）分析。还确定了氟康唑预防的效果。我们的数据表明，所建立的模型模拟了隐球菌性脑膜炎的临床症状。在单一治疗中，氟康唑（30 mg/kg）比两性霉素B或氟胞嘧啶更有效（P < 0.0001）。联合治疗导致抗隐球菌活性显著增加，高剂量氟康唑 + 氟胞嘧啶的联合治疗效果最佳（P < 0.0001）。然而，高剂量氟康唑治疗加用或不加用氟胞嘧啶之间未观察到显著差异（P > 0.05）。氟康唑预防导致脑内CFU显著降低。总之，感染后给予高剂量氟康唑或作为预防用药，可能对治疗和预防脑膜脑炎非常有效。
