Polyene and cytokine treatment of experimental aspergillosis.
The aim of the present study was to assess the efficacy of amphotericin B (AMB), AMB-intralipid admixture (AMB-IL) or nystatin-IL formulation (Ny-IL) in combination with granulocyte colony stimulating factor (G-CSF) in treatment of experimental murine aspergillosis. ICR mice were immunosuppressed by cyclophosphamide and 3 days later inoculated intravenously (i.v.) with Aspergillus fumigatus. Treatment was initiated 2 h later and administered for 5 consecutive days (polyenes, i.v.; G-CSF, intraperitoneally). Combination therapy, particularly G-CSF with AMB or AMB-IL, significantly increased the survival rate (up to 87.3%) and prolonged the mean survival time (MST) (up to 28.8 days) in comparison to untreated controls (0% survival, MST 6.7 days) and to treatment with polyenes alone (up to 51.5% survival, MST 18.4 days). These data indicate that combination therapy could be beneficial for management of disseminated aspergillosis in humans.
Sionov
Edward
E
Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
Segal
Esther
E
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy* / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology*; D003520:Cyclophosphamide / Q000494:pharmacology; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007668:Kidney / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008813:Mice, Inbred ICR; D009761:Nystatin / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010715:Phosphatidylglycerols / Q000494:pharmacology*; D016019:Survival Analysis
D000935:Antifungal Agents; D004338:Drug Combinations; D007166:Immunosuppressive Agents; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D009761:Nystatin; D016179:Granulocyte Colony-Stimulating Factor; D000666:Amphotericin B; D003520:Cyclophosphamide