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Efficacy of SCH 39304 in treatment of experimental invasive aspergillosis
T F Patterson1, D George, R Ingersoll
1Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Abstract:
The efficacy of SCH 39304 (SCH) against Aspergillus fumigatus was assessed with an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Therapy with SCH at 10 or 15 mg/kg of body weight per day was begun 24 h after lethal challenge and compared with therapy with amphotericin B at 1.5 mg/kg/day. Compared with untreated controls, SCH reduced mortality and also reduced the tissue burden of A. fumigatus 100- to 1,000-fold in liver, kidney, and lung tissues. SCH at 15 mg/kg/day and amphotericin B eliminated A. fumigatus in liver, kidney, and lung tissues. In addition, both dosages of SCH significantly eliminated the organism from brain tissues, compared with controls. Both SCH and amphotericin B decreased or eliminated circulating aspergillus antigen. These results show that new azoles can be as effective as amphotericin B in eradicating the organism from tissues and offer promise in improving the treatment of invasive aspergillosis.
Insights
New azole SCH 39304 (SCH) effectively treated invasive aspergillosis in rabbits. SCH reduced mortality and fungal burden, showing promise as an alternative to amphotericin B.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Invasive aspergillosis is a serious fungal infection, particularly in immunocompromised patients.
- Amphotericin B is a standard treatment but has significant toxicity.
- Novel antifungal agents are needed to improve treatment outcomes.
Purpose of the Study:
- To evaluate the efficacy of SCH 39304 (SCH) against Aspergillus fumigatus in a rabbit model of invasive aspergillosis.
- To compare the effectiveness of SCH with amphotericin B.
Main Methods:
- An immunosuppressed, temporarily leukopenic rabbit model was used.
- Rabbits were challenged with a lethal dose of A. fumigatus.
- Treatment with SCH (10 or 15 mg/kg/day) or amphotericin B (1.5 mg/kg/day) was initiated 24 hours post-challenge.
- Mortality, tissue fungal burden, and circulating fungal antigen levels were assessed.
Main Results:
- SCH significantly reduced mortality compared to untreated controls.
- SCH reduced A. fumigatus tissue burden by 100- to 1,000-fold in liver, kidney, and lung.
- SCH at 15 mg/kg/day and amphotericin B eradicated A. fumigatus from liver, kidney, and lung tissues.
- Both dosages of SCH eliminated A. fumigatus from brain tissue.
- Both SCH and amphotericin B reduced or eliminated circulating Aspergillus antigen.
Conclusions:
- SCH 39304 demonstrates significant efficacy against invasive aspergillosis in an animal model.
- New azoles like SCH can be as effective as amphotericin B in eradicating A. fumigatus from tissues.
- SCH shows promise as a potential new treatment option for invasive aspergillosis.