Journal Article

Experimental systemic murine aspergillosis: treatment with polyene and caspofungin combination and G-CSF

Edward Sionov, Sonia Mendlovic and Esther Segal

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 3, pages 594-597
Published in print September 2005 | ISSN: 0305-7453
Published online July 2005 | e-ISSN: 1460-2091 | DOI:
Experimental systemic murine aspergillosis: treatment with polyene and caspofungin combination and G-CSF

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  • Medical Oncology
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Objectives: In view of the poor therapy outcomes of invasive aspergillosis, the objective of this study was to evaluate the efficacy of combination treatment consisting of the polyene amphotericin-B-intralipid, the echinocandin caspofungin and granulocyte-colony stimulating factor (G-CSF) in experimental murine systemic aspergillosis. With inhibition of synthesis of 1,3-β-d-glucan in the fungal cell wall by caspofungin and an effect on the cell membrane by amphotericin-B-intralipid, this treatment may result in a synergic effect against Aspergillus fumigatus. Addition of G-CSF may further contribute to therapy of aspergillosis.

Methods: ICR mice were immunosuppressed by intraperitoneal administration of cyclophosphamide. Three days later, the mice were inoculated intravenously (iv) with A. fumigatus conidia. Infection and treatment were evaluated during an observation period of 30 days in terms of mortality (survival rate and mean survival time) and morbidity (quantitative determination of fungal burden, histopathology, and detection of serum galactomannan).

Results: Combination of caspofungin + G-CSF or addition of G-CSF to the combination of caspofungin + amphotericin-B-intralipid increased the survival rate of infected mice up to 78.9% and prolonged their mean survival time to 25 days. These combinations also resulted in a reduction in fungal burden in organs, and a decrease in serum galactomannan.

Conclusions: The successful results obtained in the experimental model may possibly open the way to more effective management of aspergillosis in humans.

Keywords: aspergillosis; caspofungin; amphotericin-B-intralipid; granulocyte-colony stimulating factor; combination therapy

Journal Article.  2114 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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