Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

dc.contributor.authorZoran, Tamara
dc.contributor.authorSartori, Bettina
dc.contributor.authorSappl, Laura
dc.contributor.authorAigner, Maria
dc.contributor.authorSánchez-Reus, Ferran
dc.contributor.authorRezusta, Antonio
dc.contributor.authorChowdhary, Anuradha
dc.contributor.authorTaj-Aldeen, Saad J.
dc.contributor.authorArendrup, Maiken C.
dc.contributor.authorOliveri, Salvatore
dc.contributor.authorKontoyiannis, Dimitrios P.
dc.contributor.authorAlastruey-Izquierdo, Ana
dc.contributor.authorLagrou, Katrien
dc.contributor.authorLo Cascio, Giuliana
dc.contributor.authorMeis, Jacques F.
dc.contributor.authorBuzina, Walter
dc.contributor.authorFarina, Claudio
dc.contributor.authorDrogari-Apiranthitou, Miranda
dc.contributor.authorGrancini, Anna
dc.contributor.authorTortorano, Anna M.
dc.contributor.authorWillinger, Birgit
dc.contributor.authorHamprecht, Axel
dc.contributor.authorJohnson, Elizabeth
dc.contributor.authorKlingspor, Lena
dc.contributor.authorArsic-Arsenijevic, Valentina
dc.contributor.authorCornely, Oliver A.
dc.contributor.authorMeletiadis, Joseph
dc.contributor.authorPrammer, Wolfgang
dc.contributor.authorTullio, Vivian
dc.contributor.authorVehreschild, Jörg-Janne
dc.contributor.authorTrovato, Laura
dc.contributor.authorLewis, Russell E.
dc.contributor.authorSegal, Esther
dc.contributor.authorRath, Peter-Michael
dc.contributor.authorHamal, Petr
dc.contributor.authorRodriguez-Iglesias, Manuel
dc.contributor.authorRoilides, Emmanuel
dc.contributor.authorArikan-Akdagli, Sevtap
dc.contributor.authorChakrabarti, Arunaloke
dc.contributor.authorColombo, Arnaldo L.
dc.contributor.authorFernández, Mariana S.
dc.contributor.authorMartin-Gomez, M. Teresa
dc.contributor.authorBadali, Hamid
dc.contributor.authorPetrikkos, Georgios
dc.contributor.authorKlimko, Nikolai
dc.contributor.authorHeimann, Sebastian M.
dc.contributor.authorUzun, Omrum
dc.contributor.authorRoudbary, Maryam
dc.contributor.authorde la Fuente, Sonia
dc.contributor.authorHoubraken, Jos
dc.contributor.authorRisslegger, Brigitte
dc.contributor.authorLass-Flörl, Cornelia
dc.contributor.authorLackner, Michaela
dc.description.abstractObjectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions: Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.en_US
dc.description.departmentMolecular Microbiology and Immunologyen_US
dc.description.sponsorshipECMM; ISHAM; EFISG; Investigator Initiated Studies Program of Astellas, MSD, and Pfizer; Christian Doppler Laboratory for invasive fungal infectionsen_US
dc.identifier.citationZoran, T., Sartori, B., Sappl, L., Aigner, M., Sánchez-Reus, F., Rezusta, A., . . . Lackner, M. (2018). Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? Frontiers in Microbiology, 9. doi:10.3389/fmicb.2018.00516en_US
dc.publisherFrontiers Mediaen_US
dc.rightsAttribution 3.0 United States*
dc.subjectcryptic speciesen_US
dc.subjectAspergillus section Terreien_US
dc.subjectsusceptibility profilesen_US
dc.subjectCyp51A alterationsen_US
dc.titleAzole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?en_US


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