Aspergillosis is a life-threatening invasive mold infection that affects severely immunosuppressed patients, such as cancer patients of the hematopoietic system, bone marrow and organ transplant recipients. The incidence of aspergillosis continues to increase and remains a main cause of morbidity and mortality in this population. Treatment of aspergillosis is problematic and still unsatisfactory. We found in previous studies that polyene-intralipid admixtures (amphotericin B-intralipid (AMB-IL) and nystatin-intralipid (Ny-IL)) were effective and less toxic than the standard formulations of these polyenes. In the present study we examined the activity of granulocyte colony-stimulating factor (G-CSF) against experimental murine aspergillosis in combination with AMB, AMB-IL or Ny-IL admixtures. An experimental animal model of systemic aspergillosis was adapted by intravenous (iv) inoculation of immunocompromised ICR mice with spores of A.fumigatus (ATCC 64026). Immunosuppression was achieved by intraperitoneal (ip) administration of 200 mg/kg of cyclophosphamide, 3 days prior to infection with the fungus. Treatment began 2 hrs after inoculation of A.fumigatus. Treatment consisted of 5 consecutive daily administrations of a combination of G-CSF and either AMB, AMB-IL or Ny-IL. G-CSF was administered ip at a dose of 150 mg/kg/day. AMB, AMB-IL or Ny-IL were administered iv at doses of 1 mg/kg/day (AMB) or 4 mg/kg/day (Ny). The mean survival rate (MSR) and mean survival time (MST) were evaluated during an observation period of 30 days. The experiments revealed that the combination therapy, particularly G-CSF with AMB or AMB-IL, led up to 90% survival of the treated mice, in comparison to 0% of the untreated controls and 39.7-48% of the animals treated by the polyenes without the cytokine. In addition, the combination therapy prolonged the MST of the mice up to 29.2 days, in comparison to MST of 6.13 days in untreated controls and 12.4-17.3 days in animals treated with polyenes alone. These promising results suggest that a similar approach could possibly be undertaken for management of aspergillosis in humans.
Full conference title:
The 15 th Congress of the International Society for Human and Animal Mycology
- ISHAM 15th (2003)