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Combination therapy in experimental invasive aspergillosis
D George1, D Kordick, P Miniter
1Yale University School of Medicine, Dept. of Medicine, New Haven, CT 06510.
Abstract:
Combination antifungal therapy was assessed in an immunosuppressed rabbit model of invasive aspergillosis. Treatment with fluconazole, amphotericin B, or a combination of both significantly prolonged survival of animals lethally challenged with Aspergillus fumigatus. High-dose amphotericin B was the most effective therapy for invasive aspergillosis. Although no antagonism was seen when fluconazole was given prophylactically or therapeutically in combination with amphotericin B, combination therapy did not augment the antifungal activity of amphotericin B. Animals given a sublethal challenge of A. fumigatus had lower mortality rates when given amphotericin B, fluconazole as treatment or prophylaxis, or various combination therapies. Only animals treated with flucytosine had mortality rates comparable to those of controls. No antagonism was observed with combinations of fluconazole and amphotericin B, flucytosine and amphotericin B, or fluconazole and flucytosine. These observations provide evidence that fluconazole, flucytosine, and amphotericin B used in various combinations are not antagonistic and may provide some insight into the treatment of invasive aspergillosis in humans.
Insights
Combination antifungal therapy, including fluconazole and amphotericin B, prolonged survival in a rabbit model of invasive aspergillosis. High-dose amphotericin B was most effective, with no antagonism observed in combined treatments.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Pharmacology
Background:
- Invasive aspergillosis is a serious fungal infection, particularly in immunocompromised individuals.
- Optimal antifungal treatment strategies, especially combination therapies, require further investigation.
Purpose of the Study:
- To evaluate the efficacy of combination antifungal therapy against invasive aspergillosis.
- To assess potential antagonism between fluconazole, amphotericin B, and flucytosine.
Main Methods:
- An immunosuppressed rabbit model was used to study invasive aspergillosis.
- Animals were treated with fluconazole, amphotericin B, or combinations thereof.
- Survival rates and mortality were monitored following challenge with Aspergillus fumigatus.
Main Results:
- Combination therapy with fluconazole and amphotericin B prolonged survival.
- High-dose amphotericin B demonstrated the highest efficacy.
- No antagonism was observed between fluconazole and amphotericin B, or flucytosine and amphotericin B, or fluconazole and flucytosine.
Conclusions:
- Combination antifungal therapies, including fluconazole and amphotericin B, are not antagonistic.
- High-dose amphotericin B is a highly effective treatment for invasive aspergillosis.
- Findings may inform human treatment strategies for invasive aspergillosis.