Treatment of murine systemic aspergillosis with polyene-intralipid admixtures.
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.
Sionov
Edward
E
Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Segal
Esther
E
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage*; D005260:Female; D016867:Immunocompromised Host / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D051379:Mice; D008813:Mice, Inbred ICR; D009761:Nystatin / Q000627:therapeutic use*; D010713:Phosphatidylcholines / Q000627:therapeutic use*; D010715:Phosphatidylglycerols / Q000627:therapeutic use*; D011090:Polyenes
D000935:Antifungal Agents; D004338:Drug Combinations; D005217:Fat Emulsions, Intravenous; D007166:Immunosuppressive Agents; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D011090:Polyenes; C068538:liposomal amphotericin B; D009761:Nystatin; D000666:Amphotericin B