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Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon
T. Zoran, B. Sartori, L. Sappl, M. Aigner, F. Sánchez-Reus, A. Rezusta, A. Chowdhary, SJ. Taj-Aldeen, MC. Arendrup, S. Oliveri, DP. Kontoyiannis, A. Alastruey-Izquierdo, K. Lagrou, GL. Cascio, JF. Meis, W. Buzina, C. Farina, M....
Language English Country Switzerland
Document type Journal Article
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- Journal Article MeSH
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.
A O U Policlinico Vittorio Emanuele Catania Biometec University of Catania Catania Italy
Clinical Microbiology Puerta del Mar University Hospital University of Cádiz Cádiz Spain
Department 1 for Internal Medicine University Hospital of Cologne Cologne Germany
Department of Biomedical and Biotechnological Sciences University of Catania Catania Italy
Department of Biomedical Sciences for Health Università degli Studi di Milano Milan Italy
Department of Dermatology Hospital Ernest Lluch Martin Zaragoza Spain
Department of Hygiene and Medical Microbiology Klinikum Wels Grieskirchen Wels Austria
Department of Medical Microbiology Hacettepe University Medical School Ankara Turkey
Department of Medical Mycology Vallabhbhai Patel Chest Institute University of Delhi New Delhi India
Department of Microbiology and Immunology KU Leuven Leuven Belgium
Department of Public Health and Pediatrics Microbiology Division Turin Italy
Division of Hygiene and Medical Microbiology Medical University of Innsbruck Innsbruck Austria
Escola Paulista de Medicina Federal University of São Paulo São Paulo Brazil
Institute for Medical Microbiology Immunology and Hygiene University of Cologne Cologne Germany
Institute of Hygiene Microbiology and Environmental Medicine Medical University of Graz Graz Austria
Microbiologia Hospital Universitario Miguel Servet IIS Aragon Universidad de Zaragoza Zaragoza Spain
Microbiology Institute ASST Papa Giovanni XXIII Bergamo Italy
Mycology Reference Laboratory Public Health England Bristol United Kingdom
National Centre for Microbiology Instituto de Salud Carlos 3 Madrid Spain
School of Medicine European University Cyprus Nicosia Cyprus
Servei de Microbiologia Hospital de la Santa Creu 1 Sant Pau Barcelona Spain
University of Texas MD Anderson Cancer Center Houston TX United States
References provided by Crossref.org
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- $a Zoran, Tamara $u Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
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- $a Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon / $c T. Zoran, B. Sartori, L. Sappl, M. Aigner, F. Sánchez-Reus, A. Rezusta, A. Chowdhary, SJ. Taj-Aldeen, MC. Arendrup, S. Oliveri, DP. Kontoyiannis, A. Alastruey-Izquierdo, K. Lagrou, GL. Cascio, JF. Meis, W. Buzina, C. Farina, M. Drogari-Apiranthitou, A. Grancini, AM. Tortorano, B. Willinger, A. Hamprecht, E. Johnson, L. Klingspor, V. Arsic-Arsenijevic, OA. Cornely, J. Meletiadis, W. Prammer, V. Tullio, JJ. Vehreschild, L. Trovato, RE. Lewis, E. Segal, PM. Rath, P. Hamal, M. Rodriguez-Iglesias, E. Roilides, S. Arikan-Akdagli, A. Chakrabarti, AL. Colombo, MS. Fernández, MT. Martin-Gomez, H. Badali, G. Petrikkos, N. Klimko, SM. Heimann, O. Uzun, M. Roudbary, S. de la Fuente, J. Houbraken, B. Risslegger, C. Lass-Flörl, M. Lackner,
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- $a 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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