JAC Advance Access originally published online on July 8, 2005
Journal of Antimicrobial Chemotherapy 2005 56(3):594-597; doi:10.1093/jac/dki252
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Experimental systemic murine aspergillosis: treatment with polyene and caspofungin combination and G-CSF
1 Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, 69978, Israel; 2 Institute of Pathology, Assaf Harofe Medical Center, Zerifin, Israel
Received 21 April 2005; returned 31 May 2005; revised 15 June 2005; accepted 21 June 2005
* Corresponding author. Tel: +972-3-6409870; Fax: +972-3-6422494; E-mail: segale{at}post.tau.ac.il
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-ß-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
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