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Efficacy of fluconazole in experimental invasive aspergillosis
T F Patterson1, P Miniter, V T Andriole
1Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Insights
Fluconazole demonstrated antifungal activity against invasive aspergillosis in rabbits, reducing fungal burden. While amphotericin B was more potent, fluconazole warrants further investigation for treating this serious infection.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Invasive aspergillosis is a serious fungal infection, particularly in immunocompromised patients.
- Developing effective antifungal therapies is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the efficacy of fluconazole against Aspergillus fumigatus in an established rabbit model of invasive aspergillosis.
- To compare fluconazole's performance with amphotericin B, a standard antifungal treatment.
Main Methods:
- An immunosuppressed, temporarily leukopenic rabbit model was used to induce invasive aspergillosis.
- Fluconazole (60 mg/kg twice daily) and amphotericin B (1.5 mg/kg/day IV) were administered and compared to untreated controls.
- Tissue burden of Aspergillus, circulating antigen levels, and survival rates were assessed.
Main Results:
- Fluconazole significantly reduced Aspergillus tissue burden in the liver, kidney, and lung (10- to 100-fold) compared to controls.
- Amphotericin B demonstrated superior efficacy in sterilizing tissues and reducing fungal burden.
- Both fluconazole and amphotericin B reduced circulating Aspergillus antigen and improved survival rates.
Conclusions:
- Fluconazole exhibits significant antifungal activity in a rabbit model of invasive aspergillosis.
- Further evaluation of fluconazole is warranted for the treatment of invasive aspergillosis.
Abstract:
The efficacy of fluconazole against Aspergillus fumigatus was evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Fluconazole was given at a dosage of 60 mg/kg twice daily and was compared with amphotericin B given intravenously at a dosage of 1.5 mg/(kg.d). Fluconazole reduced the tissue burden of Aspergillus from that in untreated controls by 10- to 100-fold in liver, kidney, and lung. However, at these doses amphotericin B was more effective in sterilizing tissues and in reducing the tissue burden of Aspergillus in those organs. Both fluconazole and amphotericin B decreased or eliminated circulating Aspergillus antigen and improved survival over that of untreated controls. Thus fluconazole shows activity in this rabbit model of invasive aspergillosis and should be further evaluated for use in the treatment of this disease.