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Abstract:
The experimentally induced aspergillosis of mice is discussed as a useful parameter for the screening of new antimycotics. There are important differences between this test model and aspergillus infections in humans. Mice must be infected intravenously with more than 10(6) spores of Aspergillus fumigatus to provoke multiple abscess formation in the kidneys which induces an acute, lethal course of infection. Intratracheal administration of 2 x 10(6) spores did not evoke any symptoms. The therapeutic efficacy of several antimycotics was examined; amphotericin B, 5-fluorocytosine and BAY h 4364--as the only imidazole-derivative--proved to be effective.
Insights
This study evaluates a mouse model for screening antifungal drugs against Aspergillus fumigatus. Intravenous infection effectively induced lethal aspergillosis, showing promise for antimycotic drug development.
Area of Science:
- Medical Mycology
- Pharmacology
Background:
- Aspergillosis, a fungal infection caused by Aspergillus species, poses a significant threat, necessitating effective treatments.
- Developing new antimycotic agents requires reliable preclinical models to assess therapeutic efficacy.
Purpose of the Study:
- To evaluate the utility of experimentally induced murine aspergillosis as a model for screening novel antimycotic compounds.
- To investigate the differences between the mouse model and human aspergillus infections.
Main Methods:
- Mice were infected intravenously with Aspergillus fumigatus spores ( > 10^6) to induce kidney abscesses and lethal infection.
- Intratracheal inoculation with 2 x 10^6 spores did not result in observable symptoms.
- The efficacy of various antimycotic agents, including amphotericin B, 5-fluorocytosine, and the imidazole derivative BAY h 4364, was assessed.
Main Results:
- Intravenous infection with a high dose of Aspergillus fumigatus spores reliably induced acute, lethal aspergillosis in mice, characterized by kidney abscess formation.
- Intratracheal administration of spores did not elicit a disease response.
- Amphotericin B, 5-fluorocytosine, and BAY h 4364 demonstrated significant therapeutic efficacy in the mouse model.
Conclusions:
- Experimentally induced murine aspergillosis via intravenous inoculation is a viable model for screening antimycotic drugs.
- The model highlights key differences from human infections, particularly regarding infectious dose and route.
- Effective agents like amphotericin B, 5-fluorocytosine, and BAY h 4364 show promise for treating aspergillosis.