Sionov Edward, Segal Esther
Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Med Mycol. 2004 Feb;42(1):73-80. doi: 10.1080/13693780310001598871.
The objective of this research was the evaluation of the activity of admixtures of amphotericin B (AMB)--intralipid (AMB-IL) and nystatin (Ny)--intralipid (Ny-IL) against experimental systemic aspergillosis in immunocompromised mice. ICR mice were transiently immunosuppressed by intraperitoneal (i.p.) administration of cyclophosphamide (CY). Three days post CY administration the mice were inoculated intravenously (i.v.) with Aspergillus fumigatus conidia. The animals were treated with various doses of AMB-IL or Ny-IL admixtures administered i.v. for 5 consecutive days, starting 2 h after infection. The mean survival rate (MSR) and mean survival time (MST) were evaluated during an observation period of 30 days in comparison to untreated infected mice and to animals treated with conventional formulations of these drugs. These experiments showed that AMB-IL increased significantly the MSR. Specifically, the MSR ranged in dependence of dose, between 48 and 65.7% vs. 0% of the untreated (P < 0.001, anova analysis) and 39.7% of AMB-treated animals (P < 0.01). The MSR of the Ny-IL-treated mice ranged between 16.2 and 40% in comparison to 0% of the untreated group (P < 0.001). Treatment with both admixtures prolonged the MST of the mice (AMB-IL: 17.3-23.07 days; Ny-IL: 8.61-16.8 days) in comparison to either untreated (6.13 days) or AMB treated animals (15.23 days). The data obtained in this study show that both AMB-IL and Ny-IL formulations, particularly AMB-IL at the highest dose, were effective in the treatment of experimental systemic aspergillosis.
本研究的目的是评估两性霉素B（AMB）-脂质体（AMB-IL）和制霉菌素（Ny）-脂质体（Ny-IL）混合物对免疫受损小鼠实验性系统性曲霉病的活性。通过腹腔注射环磷酰胺（CY）使ICR小鼠暂时免疫抑制。CY给药后三天，小鼠经静脉注射烟曲霉菌分生孢子。感染后2小时开始，动物连续5天静脉注射不同剂量的AMB-IL或Ny-IL混合物进行治疗。与未治疗的感染小鼠以及用这些药物的传统制剂治疗的动物相比，在30天的观察期内评估平均存活率（MSR）和平均存活时间（MST）。这些实验表明，AMB-IL显著提高了MSR。具体而言，MSR随剂量变化，在48%至65.7%之间，而未治疗组为0%（P<0.001，方差分析），AMB治疗组为39.7%（P<0.01）。与未治疗组的0%相比，Ny-IL治疗小鼠的MSR在16.2%至40%之间（P<0.001）。与未治疗（6.13天）或AMB治疗的动物（15.23天）相比，两种混合物治疗均延长了小鼠的MST（AMB-IL：17.3 - 23.07天；Ny-IL：8.61 - 16.8天）。本研究获得的数据表明，AMB-IL和Ny-IL制剂，特别是最高剂量的AMB-IL，在治疗实验性系统性曲霉病方面是有效的。
