Graybill J R, Najvar L K, Holmberg J D, Luther M F
University of Texas Health Science Center, Audie Murphy Veterans Administration Hospital, San Antonio 78284, USA.
Antimicrob Agents Chemother. 1995 Apr;39(4):924-9. doi: 10.1128/AAC.39.4.924.
D0870 is a recently developed triazole with characteristics of a broad spectrum of activity and slow clearance by nonrenal mechanisms. Herein we have evaluated the efficacy of D0870, alone and combined with flucytosine, in a murine model of disseminated Candida tropicalis infection. Four isolates of C. tropicalis were evaluated. Two were highly susceptible in vitro to fluconazole, and two were resistant to fluconazole. All were highly susceptible to flucytosine and D0870. Animals were pretreated with 5-fluorouracil 1 day before infection because C. tropicalis has reduced virulence in immunocompetent mice. This was done to render them neutropenic for > 10 days. Mice were infected intravenously and treated orally with D0870 or fluconazole, alone or combined with flucytosine. Survival and tissue burden of the spleen and kidneys were used to evaluate the efficacy of antifungal therapy. Fluconazole was less effective for treatment of resistant C. tropicalis than susceptible C. tropicalis. D0870 was more potent than fluconazole and was effective in fluconazole-resistant isolates. Flucytosine was consistently effective when used alone but did not consistently add to the benefit of D0870 or fluconazole. D0870 has potential in treatment of candidiasis caused by C. tropicalis, including fluconazole-resistant isolates.
D0870是一种最近研发的三唑类药物，具有广谱活性且通过非肾脏机制清除缓慢的特点。在此，我们在播散性热带念珠菌感染的小鼠模型中评估了D0870单独使用以及与氟胞嘧啶联合使用的疗效。对四株热带念珠菌进行了评估。其中两株在体外对氟康唑高度敏感，两株对氟康唑耐药。所有菌株对氟胞嘧啶和D0870均高度敏感。由于热带念珠菌在免疫功能正常的小鼠中毒力降低，因此在感染前1天用5-氟尿嘧啶对动物进行预处理，以使它们中性粒细胞减少超过10天。小鼠经静脉感染，然后口服D0870或氟康唑，单独使用或与氟胞嘧啶联合使用。通过生存情况以及脾脏和肾脏的组织负荷来评估抗真菌治疗的疗效。氟康唑治疗耐药热带念珠菌的效果不如治疗敏感热带念珠菌。D0870比氟康唑更有效，并且对耐氟康唑菌株有效。氟胞嘧啶单独使用时始终有效，但并未始终增加D0870或氟康唑的疗效。D0870在治疗由热带念珠菌引起的念珠菌病方面具有潜力，包括耐氟康唑菌株。
