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Updated: Aug 17, 2026
Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Experimental systemic murine aspergillosis: treatment with polyene and caspofungin combination and G-CSF
Edward Sionov1, Sonia Mendlovic, Esther Segal
1Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, 69978, Israel.
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-beta-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.
Insights
Combination therapy including amphotericin-B-intralipid, caspofungin, and granulocyte-colony stimulating factor (G-CSF) significantly improved survival rates in experimental invasive aspergillosis. This novel approach reduced fungal burden and serum markers, offering hope for better human treatment outcomes.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Invasive aspergillosis presents poor therapeutic outcomes, necessitating novel treatment strategies.
- Current treatments face challenges due to the complex nature of Aspergillus fumigatus infections.
- Combination therapies are being explored to enhance efficacy against fungal pathogens.
Purpose of the Study:
- To evaluate the efficacy of a combination treatment for experimental murine systemic aspergillosis.
- The study assessed a regimen including amphotericin-B-intralipid, caspofungin, and granulocyte-colony stimulating factor (G-CSF).
- Investigated potential synergistic effects against Aspergillus fumigatus.
Main Methods:
- Immunosuppressed ICR mice were infected intravenously with Aspergillus fumigatus conidia.
- Treatment efficacy was evaluated over 30 days, monitoring mortality and morbidity.
- Key metrics included survival rates, mean survival time, fungal burden in organs, histopathology, and serum galactomannan levels.
Main Results:
- Combination therapy with caspofungin + G-CSF, or caspofungin + amphotericin-B-intralipid + G-CSF, increased survival rates to 78.9%.
- Mean survival time was extended to 25 days in treated groups.
- Significant reductions in fungal burden and serum galactomannan were observed.
Conclusions:
- The studied combination therapy demonstrated significant success in an experimental model of invasive aspergillosis.
- These findings suggest a potential for more effective clinical management of human aspergillosis.
- The combination of antifungals with G-CSF warrants further investigation for treating invasive fungal infections.
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