AUTHOR=Zoran Tamara , Sartori Bettina , Sappl Laura , Aigner Maria , Sánchez-Reus Ferran , Rezusta Antonio , Chowdhary Anuradha , Taj-Aldeen Saad J. , Arendrup Maiken C. , Oliveri Salvatore , Kontoyiannis Dimitrios P. , Alastruey-Izquierdo Ana , Lagrou Katrien , Cascio Giuliana Lo , Meis Jacques F. , Buzina Walter , Farina Claudio , Drogari-Apiranthitou Miranda , Grancini Anna , Tortorano Anna M. , Willinger Birgit , Hamprecht Axel , Johnson Elizabeth , Klingspor Lena , Arsic-Arsenijevic Valentina , Cornely Oliver A. , Meletiadis Joseph , Prammer Wolfgang , Tullio Vivian , Vehreschild Jörg-Janne , Trovato Laura , Lewis Russell E. , Segal Esther , Rath Peter-Michael , Hamal Petr , Rodriguez-Iglesias Manuel , Roilides Emmanuel , Arikan-Akdagli Sevtap , Chakrabarti Arunaloke , Colombo Arnaldo L. , Fernández Mariana S. , Martin-Gomez M. Teresa , Badali Hamid , Petrikkos Georgios , Klimko Nikolai , Heimann Sebastian M. , Uzun Omrum , Roudbary Maryam , de la Fuente Sonia , Houbraken Jos , Risslegger Brigitte , Lass-Flörl Cornelia , Lackner Michaela 

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

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.00516

DOI=10.3389/fmicb.2018.00516

ISSN=1664-302X

ABSTRACT=<p><bold>Objectives:</bold> Invasive mold infections associated with <italic>Aspergillus</italic> species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the <italic>Aspergillus</italic> section <italic>Fumigati</italic> followed by members of the section <italic>Terrei</italic>. The frequency of <italic>Aspergillus terreus</italic> and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied.</p><p><bold>Methods:</bold> A global set (<italic>n</italic> = 498) of <italic>A. terreus</italic> 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 <italic>cyp51A</italic> gene.</p><p><bold>Results:</bold> The majority of isolates was identified as <italic>A. terreus</italic> (86.8%), followed by <italic>A. citrinoterreus</italic> (8.4%), <italic>A. hortai</italic> (2.6%), <italic>A. alabamensis</italic> (1.6%), <italic>A. neoafricanus</italic> (0.2%), and <italic>A. floccosus</italic> (0.2%). One isolate failed to match a known <italic>Aspergillus</italic> sp., but was found most closely related to <italic>A. alabamensis</italic>. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of <italic>A. terreus sensu stricto (s.s.)</italic> 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 <italic>A. citrinoterreus</italic> and one <italic>A. alabamensis</italic> isolate. The most affected amino acid position of the <italic>Cyp51A</italic> gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V.</p><p><bold>Conclusions:</bold><italic>Aspergillus terreus</italic> was most prevalent, followed by <italic>A. citrinoterreus</italic>. Posaconazole was the most potent drug against <italic>A. terreus</italic>, but 5.4% of <italic>A. terreus sensu stricto</italic> showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all <italic>A. terreus</italic> isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.</p>