J Steinmann1, A Hamprecht2, M J G T Vehreschild3, O A Cornely4, D Buchheidt5, B Spiess5, M Koldehoff6, J Buer7, J F Meis8, P-M Rath7. 1. Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany joerg.steinmann@uk-essen.de. 2. Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany. 3. First Department of Internal Medicine, University of Cologne, Cologne, Germany German Centre for Infection Research (DZIF), Partner site Bonn-Cologne, Germany. 4. First Department of Internal Medicine, University of Cologne, Cologne, Germany German Centre for Infection Research (DZIF), Partner site Bonn-Cologne, Germany Clinical Trials Centre Cologne, ZKS Köln, BMBF 01KN1106, Center for Integrated Oncology CIO Köln Bonn, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. 5. 3rd Department of Internal Medicine, Mannheim University Hospital, University of Heidelberg, Mannheim, Germany. 6. Department of Bone Marrow Transplantation (AHE), West German Cancer Center, University Hospital Essen, Essen, Germany. 7. Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. 8. Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Abstract
OBJECTIVES: Aspergillus fumigatus is the most common agent of invasive aspergillosis (IA). In recent years, resistance to triazoles, the mainstay of IA therapy, has emerged in different countries worldwide. IA caused by azole-resistant A. fumigatus (ARAF) shows an exceedingly high mortality. In this study, IA due to ARAF isolates in HSCT recipients in Germany was investigated. METHODS: The epidemiology of azole resistance in IA was analysed in two German haematology departments. Between 2012 and 2013, 762 patients received HSCT in Essen (n = 388) and Cologne (n = 374). Susceptibility testing of A. fumigatus isolates was performed by Etest, followed by EUCAST broth microdilution testing if elevated MICs were recorded. In all ARAF isolates the cyp51A gene was sequenced and the genotype was determined by microsatellite typing using nine short tandem repeats. RESULTS: In total, A. fumigatus was recovered from 27 HSCT recipients. Eight patients had azole-resistant IA after HSCT, and seven of the cases were fatal (88%). All except one patient received antifungal prophylaxis (in five cases triazoles). TR34/L98H was the most common mutation (n = 5), followed by TR46/Y121F/T289A (n = 2). In one resistant isolate no cyp51A mutation was detected. Genotyping revealed genetic diversity within the German ARAF isolates and no clustering with resistant isolates from the Netherlands, India and France. CONCLUSIONS: This report highlights the emergence of azole-resistant IA with TR34/L98H and TR46/Y121F/T289A mutations in HSCT patients in Germany and underscores the need for systematic antifungal susceptibility testing of A. fumigatus.
OBJECTIVES:Aspergillus fumigatus is the most common agent of invasive aspergillosis (IA). In recent years, resistance to triazoles, the mainstay of IA therapy, has emerged in different countries worldwide. IA caused by azole-resistant A. fumigatus (ARAF) shows an exceedingly high mortality. In this study, IA due to ARAF isolates in HSCT recipients in Germany was investigated. METHODS: The epidemiology of azole resistance in IA was analysed in two German haematology departments. Between 2012 and 2013, 762 patients received HSCT in Essen (n = 388) and Cologne (n = 374). Susceptibility testing of A. fumigatus isolates was performed by Etest, followed by EUCAST broth microdilution testing if elevated MICs were recorded. In all ARAF isolates the cyp51A gene was sequenced and the genotype was determined by microsatellite typing using nine short tandem repeats. RESULTS: In total, A. fumigatus was recovered from 27 HSCT recipients. Eight patients had azole-resistant IA after HSCT, and seven of the cases were fatal (88%). All except one patient received antifungal prophylaxis (in five cases triazoles). TR34/L98H was the most common mutation (n = 5), followed by TR46/Y121F/T289A (n = 2). In one resistant isolate no cyp51A mutation was detected. Genotyping revealed genetic diversity within the German ARAF isolates and no clustering with resistant isolates from the Netherlands, India and France. CONCLUSIONS: This report highlights the emergence of azole-resistant IA with TR34/L98H and TR46/Y121F/T289A mutations in HSCT patients in Germany and underscores the need for systematic antifungal susceptibility testing of A. fumigatus.
Authors: Jacques F Meis; Anuradha Chowdhary; Johanna L Rhodes; Matthew C Fisher; Paul E Verweij Journal: Philos Trans R Soc Lond B Biol Sci Date: 2016-12-05 Impact factor: 6.237
Authors: I Montesinos; M A Argudín; M Hites; F Ahajjam; M Dodémont; C Dagyaran; M Bakkali; I Etienne; F Jacobs; C Knoop; S Patteet; K Lagrou Journal: J Clin Microbiol Date: 2017-05-17 Impact factor: 5.948
Authors: Rose-Anne Lavergne; Florent Morio; Loïc Favennec; Stéphane Dominique; Jacques F Meis; Gilles Gargala; Paul E Verweij; Patrice Le Pape Journal: Antimicrob Agents Chemother Date: 2015-04-27 Impact factor: 5.191