Azole-resistance in Aspergillus terreus and related species: An emerging problem or a rare Phenomenon?

Zoran, T. and Sartori, B. and Sappl, L. and Aigner, M. and Sánchez-Reus, F. and Rezusta, A. and Chowdhary, A. and Taj-Aldeen, S.J. and Arendrup, M.C. and Oliveri, S. and Kontoyiannis, D.P. and Alastruey-Izquierdo, A. and Lagrou, K. and Cascio, G.L. and Meis, J.F. and Buzina, W. and Farina, C. and Drogari-Apiranthitou, M. and Grancini, A. and Tortorano, A.M. and Willinger, B. and Hamprecht, A. and Johnson, E. and Klingspor, L. and Arsic-Arsenijevic, V. and Cornely, O.A. and Meletiadis, J. and Prammer, W. and Tullio, V. and Vehreschild, J.-J. and Trovato, L. and Lewis, R.E. and Segal, E. and Rath, P.-M. and Hamal, P. and Rodriguez-Iglesias, M. and Roilides, E. and Arikan-Akdagli, S. and Chakrabarti, A. and Colombo, A.L. and Fernández, M.S. and Martin-Gomez, M.T. and Badali, H. and Petrikkos, G. and Klimko, N. and Heimann, S.M. and Uzun, O. and Roudbary, M. and de la Fuente, S. and Houbraken, J. and Risslegger, B. and Lass-Flörl, C. and Lackner, M. (2018) Azole-resistance in Aspergillus terreus and related species: An emerging problem or a rare Phenomenon? Frontiers in Microbiology, 9 (MAR).

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Abstract

Objectives: 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. © 2018 Zoran, Sartori, Sappl, Aigner, Sánchez-Reus, Rezusta, Chowdhary, Taj-Aldeen, Arendrup, Oliveri, Kontoyiannis, Alastruey-Izquierdo, Lagrou, Cascio, Meis, Buzina, Farina, Drogari-Apiranthitou, Grancini, Tortorano, Willinger, Hamprecht, Johnson, Klingspor, Arsic-Arsenijevic, Cornely, Meletiadis, Prammer, Tullio, Vehreschild, Trovato, Lewis, Segal, Rath, Hamal, Rodriguez-Iglesias, Roilides, Arikan-Akdagli, Chakrabarti, Colombo, Fernández, Martin-Gomez, Badali, Petrikkos, Klimko, Heimann, Uzun, Roudbary, de la Fuente, Houbraken, Risslegger, Lass-Flörl and Lackner.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: beta tubulin; itraconazole; posaconazole; sterol 14alpha demethylase; voriconazole, antifungal resistance; antifungal susceptibility; Article; Aspergillus; Aspergillus alabamensis; Aspergillus citrinoterreus; Aspergillus floccosus; Aspergillus hortai; Aspergillus neoafricanus; Aspergillus terreus; minimum inhibitory concentration; nonhuman; phenotype; point mutation; single nucleotide polymorphism; species distribution; species diversity
Subjects: QW Microbiology. Immunology
Depositing User: eprints admin
Date Deposited: 17 Dec 2018 05:43
Last Modified: 17 Jul 2019 09:45
URI: http://eprints.iums.ac.ir/id/eprint/6789

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