Karyotakis N C, Dignani M C, Anaissie E J
Department of Internal Medicine, University of Texas Medical School, Houston.
Antimicrob Agents Chemother. 1995 Mar;39(3):775-7. doi: 10.1128/AAC.39.3.775.
Candida krusei is increasingly recognized as an opportunistic pathogen in immunocompromised patients and is inherently resistant to fluconazole. We tested the in vivo efficacy of SCH 51048, an investigational antifungal triazole, in experimental hematogenous murine infection caused by two C. krusei isolates and compared its activity with those of amphotericin B and fluconazole. CF1 mice were immunosuppressed with cyclophosphamide and cortisone acetate and were challenged intravenously with infecting inocula of each C. krusei isolate. Treatment with SCH 51048 (50 or 100 mg/kg of body weight per day orally) or amphotericin B (2 mg/kg/day intraperitoneally) significantly prolonged the survival of infected mice and significantly reduced fungal titers in the kidneys (P < or = 0.05). Treatment with fluconazole (100 mg/kg/day orally) had no effect. Both dosages of SCH 51048 were as effective as amphotericin B in improving survival, but the higher dosage was significantly (P < or = 0.05) better in reducing the fungal burden in the kidneys of infected animals. A dose-dependent response was observed with SCH 51048 treatment, especially in organ clearance. Our results indicate that SCH 51048 is the first triazole that has in vivo activity against experimental infection with C. krusei and deserves further evaluation.
克柔念珠菌越来越被认为是免疫功能低下患者的一种机会性病原菌，并且其对氟康唑天然耐药。我们测试了一种研究性抗真菌三唑类药物SCH 51048在由两株克柔念珠菌分离株引起的实验性血源性小鼠感染中的体内疗效，并将其活性与两性霉素B和氟康唑的活性进行了比较。CF1小鼠用环磷酰胺和醋酸可的松进行免疫抑制，然后静脉注射每种克柔念珠菌分离株的感染接种物。用SCH 51048（每天口服50或100mg/kg体重）或两性霉素B（每天腹腔注射2mg/kg）治疗可显著延长感染小鼠的存活时间，并显著降低肾脏中的真菌滴度（P≤0.05）。用氟康唑（每天口服100mg/kg）治疗则无效果。SCH 51048的两种剂量在提高存活率方面与两性霉素B一样有效，但较高剂量在降低感染动物肾脏中的真菌负荷方面显著更好（P≤0.05）。观察到SCH 51048治疗有剂量依赖性反应，尤其是在器官清除方面。我们的结果表明，SCH 51048是第一种对克柔念珠菌实验性感染具有体内活性的三唑类药物，值得进一步评估。
