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Model of recurrent pulmonary aspergillosis in rats
Y Niki1, E M Bernard, F F Edwards
1Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Abstract:
Male Sprague-Dawley rats were treated with cortisone acetate and fed a low-protein diet for 3 weeks. At the end of week 2, animals were infected intratracheally with 10(5) conidia of Aspergillus fumigatus H11-20. Despite discontinuation of steroids and the low-protein diet 1 week after the infection, 94% of controls died of invasive pulmonary aspergillosis within 3 weeks postinfection. When rats were treated with a single dose of 1.6 mg of aerosolized amphotericin B per kg of body weight 48 h prior to the infection, mortality was reduced to 11% within 3 weeks postinfection. Despite apparent good health and rapid weight gain, all survivors showed multiple lesions in histopathological sections of the lungs, and 10(3) to 10(4) CFU of aspergilli was recovered from cultures of their lungs. With discontinuation of immunosuppression, the infection was slowly cleared; however, when cortisone acetate was restarted during week 5, reactivation of progressive invasive pulmonary aspergillosis was observed. On the basis of these results, we conclude that a single low dose of aerosolized amphotericin B prophylaxis is effective in preventing an exogenous aspergillus infection of the lung. Additional therapy is needed to prevent recurrent infection caused by endogenous aspergilli when immunosuppression is resumed.
Insights
A single low dose of aerosolized amphotericin B effectively prevents invasive pulmonary aspergillosis in rats. However, recurrent infections may occur if immunosuppression is resumed, requiring additional antifungal therapy.
Area of Science:
- Medical Mycology
- Pulmonology
- Pharmacology
Background:
- Invasive pulmonary aspergillosis (IPA) is a severe complication in immunocompromised individuals.
- Cortisone acetate and low-protein diets induce immunosuppression, increasing susceptibility to fungal infections.
- Aspergillus fumigatus is a common opportunistic pathogen causing IPA.
Purpose of the Study:
- To evaluate the prophylactic efficacy of aerosolized amphotericin B against IPA in an established rat model.
- To investigate the impact of immunosuppression resumption on established Aspergillus infections.
Main Methods:
- Male Sprague-Dawley rats were rendered immunosuppressed using cortisone acetate and a low-protein diet.
- Animals were intratracheally inoculated with Aspergillus fumigatus conidia.
- Prophylactic treatment involved a single dose of aerosolized amphotericin B administered 48 hours before infection.
- Immunosuppression was discontinued and later resumed to assess infection clearance and reactivation.
Main Results:
- Untreated controls exhibited 94% mortality due to IPA within 3 weeks postinfection.
- A single low dose of aerosolized amphotericin B prophylaxis reduced mortality to 11%.
- Survivors showed lung lesions and viable Aspergillus, indicating incomplete eradication.
- Resumption of cortisone acetate led to reactivation of progressive IPA.
Conclusions:
- A single low dose of aerosolized amphotericin B is effective prophylaxis against exogenous pulmonary Aspergillus infection.
- Additional antifungal therapy is necessary to prevent recurrent infections when immunosuppression is resumed, especially for endogenous fungi.