Ghannoum M A, Okogbule-Wonodi I, Bhat N, Sanati H
Center for Medical Mycology, Mycology Reference Laboratory, Case Western Reserve University, University Hospitals of Cleveland, Ohio 44106-5028, USA.
J Chemother. 1999 Feb;11(1):34-9. doi: 10.1179/joc.1999.11.1.34.
Voriconazole (UK-109,496) is a new triazole with in vitro activity against a wide spectrum of fungi including yeasts intrinsically resistant to fluconazole such as Candida krusei. In this study the efficacy of voriconazole was compared to amphotericin B and fluconazole in a neutropenic guinea pig model of hematogenously disseminated C. krusei infection. In guinea pigs, neutropenia was established by using cyclophosphamide (intraperitoneally, i.p., 100 mg/kg on day 1 and 4), and dexamethasone (orally, 2 mg/kg/day, for 8 days). Neutropenic guinea pigs were infected with 0.5 ml of yeast cell suspension (1 x 10(8) CFU) intravenously. Challenged animals were treated with antifungals starting 1 h postinfection for 7 days. The animals were divided into five groups: untreated control, amphotericin B (1 mg/kg i.p. on alternate days), fluconazole (20 mg/kg orally twice daily), and voriconazole (two groups: 5 and 10 mg/kg orally twice daily) groups. Guinea pigs were sacrificed 1 day after the last treatment. Brain, liver, and kidneys were removed and weighed, tissues were homogenized and fungal burden determined by serial quantitative counts. Voriconazole at dosages of 5 or 10 mg/kg b.i.d. was shown to be significantly more efficacious than either amphotericin B or fluconazole in eradicating C. krusei from brain, liver and kidney tissue. These data indicate that voriconazole could be efficacious for the treatment of infections caused by fluconazole-resistant Candida, such as C. krusei.
伏立康唑（UK-109,496）是一种新型三唑类药物，具有体外抗广谱真菌活性，包括对氟康唑天然耐药的酵母，如克鲁斯念珠菌。在本研究中，在中性粒细胞减少的豚鼠血行播散性克鲁斯念珠菌感染模型中，比较了伏立康唑与两性霉素B和氟康唑的疗效。在豚鼠中，通过使用环磷酰胺（腹腔注射，第1天和第4天，100mg/kg）和地塞米松（口服，2mg/kg/天，共8天）诱导中性粒细胞减少。中性粒细胞减少的豚鼠静脉注射0.5ml酵母细胞悬液（1×10⁸CFU）。感染后1小时开始用抗真菌药物治疗受挑战的动物，持续7天。动物分为五组：未治疗对照组、两性霉素B（隔天腹腔注射1mg/kg）、氟康唑（口服20mg/kg，每日两次）和伏立康唑（两组：口服5和10mg/kg，每日两次）组。最后一次治疗后1天处死豚鼠。取出脑、肝和肾并称重，将组织匀浆，通过连续定量计数确定真菌负荷。在从脑、肝和肾组织中清除克鲁斯念珠菌方面，5或10mg/kg bid剂量的伏立康唑显示出比两性霉素B或氟康唑显著更有效。这些数据表明，伏立康唑可能对治疗由氟康唑耐药念珠菌引起的感染有效，如克鲁斯念珠菌。
