TY - JOUR

T1 - Azole-resistance in Aspergillus terreus and related species

T2 - An emerging problem or a rare Phenomenon?

AU - Zoran, Tamara

AU - Sartori, Bettina

AU - Sappl, Laura

AU - Aigner, Maria

AU - Sánchez-Reus, Ferran

AU - Rezusta, Antonio

AU - Chowdhary, Anuradha

AU - Taj-Aldeen, Saad J.

AU - Arendrup, Maiken C.

AU - Oliveri, Salvatore

AU - Kontoyiannis, Dimitrios P.

AU - Alastruey-Izquierdo, Ana

AU - Lagrou, Katrien

AU - Cascio, Giuliana Lo

AU - Meis, Jacques F.

AU - Buzina, Walter

AU - Farina, Claudio

AU - Drogari-Apiranthitou, Miranda

AU - Grancini, Anna

AU - Tortorano, Anna M.

AU - Willinger, Birgit

AU - Hamprecht, Axel

AU - Johnson, Elizabeth

AU - Klingspor, Lena

AU - Arsic-Arsenijevic, Valentina

AU - Cornely, Oliver A.

AU - Meletiadis, Joseph

AU - Prammer, Wolfgang

AU - Tullio, Vivian

AU - Vehreschild, Jörg Janne

AU - Trovato, Laura

AU - Lewis, Russell E.

AU - Segal, Esther

AU - Rath, Peter Michael

AU - Hamal, Petr

AU - Rodriguez-Iglesias, Manuel

AU - Roilides, Emmanuel

AU - Arikan-Akdagli, Sevtap

AU - Chakrabarti, Arunaloke

AU - Colombo, Arnaldo L.

AU - Fernández, Mariana S.

AU - Martin-Gomez, M. Teresa

AU - Badali, Hamid

AU - Petrikkos, Georgios

AU - Klimko, Nikolai

AU - Heimann, Sebastian M.

AU - Uzun, Omrum

AU - Roudbary, Maryam

AU - de la Fuente, Sonia

AU - Houbraken, Jos

AU - Risslegger, Brigitte

AU - Lass-Flörl, Cornelia

AU - Lackner, Michaela

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Aspergillus section Terrei

KW - Azoles

KW - Cryptic species

KW - Cyp51A alterations

KW - Susceptibility profiles

U2 - 10.3389/fmicb.2018.00516

DO - 10.3389/fmicb.2018.00516

M3 - Journal article

C2 - 29643840

AN - SCOPUS:85044825355

VL - 9

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

SN - 1664-302X

IS - MAR

M1 - 516

ER -