1. Development of a Corticosteroid-Immunosuppressed Mouse Model to Study the Pathogenesis and Therapy of Influenza-Associated Pulmonary Aspergillosis.
- Author
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Wurster S, Pantaleón García J, Albert ND, Jiang Y, Bhoda K, Kulkarni VV, Wang Y, Walsh TJ, Evans S, and Kontoyiannis DP
- Subjects
- Animals, Mice, Humans, Antifungal Agents therapeutic use, Adrenal Cortex Hormones therapeutic use, Aspergillus fumigatus, Influenza, Human complications, Influenza, Human drug therapy, Pulmonary Aspergillosis complications, Pulmonary Aspergillosis drug therapy, Aspergillosis drug therapy
- Abstract
Influenza-associated pulmonary aspergillosis (IAPA) is a feared complication in patients with influenza tracheobronchitis, especially those receiving corticosteroids. Herein, we established a novel IAPA mouse model with low-inoculum Aspergillus infection and compared outcomes in mice with and without cortisone acetate (CA) immunosuppression. CA was an independent predictor of increased morbidity/mortality in mice with IAPA. Early antifungal treatment with liposomal amphotericin B was pivotal to improve IAPA outcomes in CA-immunosuppressed mice, even after prior antiviral therapy with oseltamivir. In summary, our model recapitulates key clinical features of IAPA and provides a robust preclinical platform to study the pathogenesis and treatment of IAPA., Competing Interests: Potential conflicts of interest. D. P. K. reports honoraria and research support from Gilead Sciences and Astellas Pharma; consultant fees from Astellas Pharma, Merck, and Gilead Sciences; and membership of the Data Review Committee of Cidara Therapeutics, AbbVie, and the Mycoses Study Group. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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