Artigo Acesso aberto Produção Nacional Revisado por pares

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

2018; Frontiers Media; Volume: 9; Linguagem: Inglês

10.3389/fmicb.2018.00516

ISSN

1664-302X

Autores

Tamara Zoran, Bettina Sartori, Laura Sappl, Maria Aigner, F Sánchez, Antonio Rezusta, Anuradha Chowdhary, Saad J. Taj‐Aldeen, Maiken Cavling Arendrup, Salvatore Massimo Oliveri, Dimitrios P. Kontoyiannis, Ana Alastruey‐Izquierdo, Katrien Lagrou, Giuliana Lo Cascio, Jacques F. Meis, Walter Buzina, Claudio Farina, Maria Drogari‐Apiranthitou, Anna Grancini, Anna Maria Tortorano, Birgit Willinger, Axel Hamprecht, Elizabeth M. Johnson, Lena Klingspor, Valentina Arsić‐Arsenijević, Oliver A. Cornely, Joseph Meletiadis, W. Prammer, Viviana Cristina Tullio, Jörg Janne Vehreschild, Laura Trovato, Russell E. Lewis, Esther Segal, Peter‐Michael Rath, Petr Hamal, Manuel Rodríguez‐Iglesias, Emmanuel Roilides, Sevtap Arıkan-Akdağlı, Arunaloke Chakrabarti, Arnaldo Lopes Colombo, Mariana S. Fernández, María Teresa Martín-Gómez, Hamid Badali, Γεώργιος Πετρίκκος, Н Н Климко, Sebastian Heimann, Ömrüm Uzun, Maryam Roudbary, Sonia de la Fuente, Jos Houbraken, Brigitte Risslegger, Cornelia Lass‐Flörl, Michaela Lackner,

Tópico(s)

Fungal Infections and Studies

Resumo

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.

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