DESCRIPTION (provided by applicant): Aspergillus fumigatus causes a wide spectrum of diseases including allergic syndromes, chronic pulmonary aspergillosis and acute invasive aspergillosis (IA). Triazole antifungal drugs play an important role in the management of Aspergillus diseases, as they represent first-line therapy for all forms of aspergillosis and comprise the only orally active group of antifungal agents. The rapid increase in triazole resistant Aspergillus infections is a growing public health and patient management concern. Evidence has been accumulating that A. fumigatus can develop resistance during prolonged azole treatment, which exceeds 10% in patients with chronic disease. In contrast, the resistance rates in patients with acute IA, such as with transplant patients, is rather low (90% of the triazole resistance in A. fumigatus. A statistical correlation will be used to assess the presence of underlying resistant strains in the two populations. Most importantly, the impact of acquired triazole resistance on the pathogen fitness will be examined in vivo. The relative fitness of mutant and wild-type strains will be assessed by a mixed challenge approach in a murine model of invasive pulmonary aspergillosis. This work takes advantage of new molecular tools and strong preliminary data developed by our group, and access to important clinical respiratory specimens from patients with chronic disease, including cystic fibrosis, and acute disease. This work will greatly advance our understanding of the importance of triazole resistance in the management of patients with chronic Aspergillus and allergic disease requiring prolonged antifungal therapy.
|Effective start/end date||4/15/13 → 3/31/16|
- National Institutes of Health: $195,451.00
- National Institutes of Health: $198,750.00
- National Institutes of Health: $43,006.00
- Immunology and Microbiology(all)