Major variations in Aspergillus fumigatus arising within aspergillomas in chronic pulmonary aspergillosis. Issue 4 (1st February 2013)

• Record Type: Journal Article
• Authors: Howard, S. J.; Pasqualotto, A. C.; Anderson, M. J.; Leatherbarrow, H.; Albarrag, A. M.; Harrison, E.; Gregson, L.; Bowyer, P.; Denning, D. W.
• Is Part Of: Mycoses. Volume 56:Issue 4(2013)
• Page Start: 434
• Page End: 441
• Publication Date: 2013-02-01
• Subjects: Pathogenic fungi -- Periodicals; Medical mycology -- Periodicals; 616.969
• DOI: 10.1111/myc.12047
• Languages: English
• ISSNs: 0933-7407

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Summary</title> <p>Aspergillomas develop from progressive layers of mycelial growth on the walls of pulmonary cavities over months. Aspergillomas are characteristic of chronic pulmonary aspergillosis and are a risk factor for azole resistance. We investigated genotypic and phenotypic alterations in <italic>Aspergillus fumigatus</italic> recovered from aspergillomas. Aspergillomas were removed from three patients (two at surgery, one at autopsy) and dissected. Overall 92 colonies of <italic>A. fumigatus</italic> were isolated. Microsatellite typing was conducted to determine genetic type. Itraconazole, voriconazole and posaconazole susceptibilities were performed. The <italic>cyp51A</italic> gene was sequenced in 22 isolates. Isolates from Patient 1 (<italic>n </italic>= 25) were azole susceptible and resistant, although all <italic>cyp51A</italic> sequences were wild type, the isolates split into two distinct clades. In Patient 2, isolates were less variable (<italic>n </italic>= 10), all were azole susceptible. In Patient 3 only azole‐resistant strains (<italic>n </italic>= 57) were isolated, with M220K or M220T Cyp51A alterations, and microevolution was indicated. Marked diversity was observed in isolates from these patients; revealing differences in azole susceptibility, mechanism of resistance and genetic type. Importantly, routine sampling from respiratory specimens proved suboptimal in all cases; azole resistance was missed (Patient 1), cultures were negative (Patient 2) and high‐level posaconazole resistance was not detected (Patient 3).</p> </abstract>