Lichtheimia corymbifera Colonization Leading to Pulmonary Infection Can Be Prevented with Liposomal Amphotericin B in a New Murine Model

The incidence of pulmonary mucormycosis is constantly increasing, especially in hematological patients staying in high-efficiency particulate air-filtered rooms. Pulmonary inhalation of spores may occur outside the hospital, leading to invasive disease once patients received chemotherapies. We devel...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2019-08, Vol.63 (8)
Main Authors: Brunet, Thomas, Brunet, Kévin, Jouvion, Grégory, Cateau, Estelle, Marchand, Sandrine, Rammaert, Blandine
Format: Article
Language:English
Subjects:
Amphotericin B
Antifungal Agents
Experimental Therapeutics
Life Sciences
Mucormycosis
Pharmaceutical sciences
Respiratory Tract Infections
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Summary:The incidence of pulmonary mucormycosis is constantly increasing, especially in hematological patients staying in high-efficiency particulate air-filtered rooms. Pulmonary inhalation of spores may occur outside the hospital, leading to invasive disease once patients received chemotherapies. We developed a new pulmonary mucormycosis mouse model mimicking the expected pathophysiology in human to study antifungal drugs. Naive mice were inoculated intratracheally with spores. After 3 days, mice received corticosteroids and cyclophosphamide and secondarily developed the disease, while only 5% of the initial inoculum was present in the lungs at day 3. Lung colonization with spores in immunocompetent mice can last at least 44 days. Antifungal drug was administered the day of immunosuppression. Injection of a single 15 mg/kg of body weight dose of liposomal amphotericin B significantly improved survival and pulmonary fungal burden compared with controls, whereas 80 mg/kg oral posaconazole did not. These results show that a unique dose of liposomal amphotericin B offers a real potential decolonization treatment to prevent infection in our mouse model of lung colonization followed by lung infection.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.02544-18