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Treatment of murine coccidioidal meningitis with fluconazole (UK 49,858)
Abstract:
Male ICR mice were challenged intracerebrally with endospores of Coccidioides immitis and then treated with water (control), fluconazole, amphotericin B (Fungizone), or ketoconazole (Nizoral). All three drugs markedly prolonged survival, and all three drugs lowered brain colony counts of C. immitis. Survival of mice treated orally with fluconazole at the high dose was longer than in the ketoconazole treated group. Amphotericin B was more efficacious than fluconazole. Further investigations are needed to determine the efficacy of fluconazole in treatment of coccidioidal meningitis.
Insights
This study evaluated antifungal drugs for treating Coccidioides immitis brain infections in mice. Amphotericin B showed the highest efficacy, while fluconazole and ketoconazole also prolonged survival.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Coccidioides immitis causes fungal infections, including potentially fatal meningitis.
- Effective treatment options for severe coccidioidal infections, particularly neurococcidioidomycosis, are crucial.
Purpose of the Study:
- To compare the efficacy of fluconazole, amphotericin B, and ketoconazole in a murine model of Coccidioides immitis brain infection.
- To assess the impact of these antifungal agents on survival rates and fungal burden in the brain.
Main Methods:
- Male ICR mice were intracerebrally inoculated with Coccidioides immitis endospores.
- Mice were subsequently treated with water (control), fluconazole, amphotericin B (Fungizone), or ketoconazole (Nizoral).
- Survival times and brain C. immitis colony counts were measured.
Main Results:
- All tested antifungal drugs (fluconazole, amphotericin B, ketoconazole) significantly prolonged survival compared to the control group.
- These drugs also led to a reduction in C. immitis colony counts within the brain.
- Amphotericin B demonstrated superior efficacy compared to fluconazole.
- High-dose oral fluconazole resulted in longer survival than ketoconazole.
Conclusions:
- Fluconazole, amphotericin B, and ketoconazole show promise in treating experimental Coccidioides immitis brain infections.
- Amphotericin B is more effective than fluconazole in this model.
- Further research is warranted to establish the clinical utility of fluconazole for coccidioidal meningitis.