{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:23:26Z","timestamp":1791933806152,"version":"4.3.4"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u200a=\u200a388) and Cologne (n\u200a=\u200a374). 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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\u200a=\u200a5), followed by TR46\/Y121F\/T289A (n\u200a=\u200a2). 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dku566","type":"journal-article","created":{"date-parts":[[2015,1,29]],"date-time":"2015-01-29T04:31:38Z","timestamp":1422505898000},"page":"1522-1526","source":"Crossref","is-referenced-by-count":177,"title":["Emergence of azole-resistant invasive aspergillosis in HSCT recipients in Germany"],"prefix":"10.1093","volume":"70","author":[{"given":"J.","family":"Steinmann","sequence":"first","affiliation":[{"name":"1 \u00a0Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Hamprecht","sequence":"additional","affiliation":[{"name":"2 \u00a0Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J. G. T.","family":"Vehreschild","sequence":"additional","affiliation":[{"name":"3 \u00a0First Department of Internal Medicine, University of Cologne, Cologne, Germany"},{"name":"4 \u00a0German Centre for Infection Research (DZIF), Partner site Bonn-Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O. A.","family":"Cornely","sequence":"additional","affiliation":[{"name":"3 \u00a0First Department of Internal Medicine, University of Cologne, Cologne, Germany"},{"name":"4 \u00a0German Centre for Infection Research (DZIF), Partner site Bonn-Cologne, Germany"},{"name":"5 \u00a0Clinical Trials Centre Cologne, ZKS K\u00f6ln, BMBF 01KN1106, Center for Integrated Oncology CIO K\u00f6ln Bonn, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Buchheidt","sequence":"additional","affiliation":[{"name":"6 \u00a03rd Department of Internal Medicine, Mannheim University Hospital, University of Heidelberg, Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Spiess","sequence":"additional","affiliation":[{"name":"6 \u00a03rd Department of Internal Medicine, Mannheim University Hospital, University of Heidelberg, Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Koldehoff","sequence":"additional","affiliation":[{"name":"7 \u00a0Department of Bone Marrow Transplantation (AHE), West German Cancer Center, University Hospital Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Buer","sequence":"additional","affiliation":[{"name":"1 \u00a0Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. F.","family":"Meis","sequence":"additional","affiliation":[{"name":"8 \u00a0Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands"},{"name":"9 \u00a0Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.-M.","family":"Rath","sequence":"additional","affiliation":[{"name":"1 \u00a0Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,1,27]]},"reference":[{"key":"2022020121022986200_DKU566C1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1086\/510592","article-title":"Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality","volume":"44","author":"Upton","year":"2007","journal-title":"Clin Infect Dis"},{"key":"2022020121022986200_DKU566C2","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1086\/525258","article-title":"Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America","volume":"46","author":"Walsh","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2022020121022986200_DKU566C3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00277-008-0622-5","article-title":"Treatment of invasive fungal infections in cancer patients\u2014recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)","volume":"88","author":"Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)","year":"2009","journal-title":"Ann Hematol"},{"key":"2022020121022986200_DKU566C4","doi-asserted-by":"crossref","first-page":"e1003633","DOI":"10.1371\/journal.ppat.1003633","article-title":"Emergence of azole-resistant Aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health","volume":"9","author":"Chowdhary","year":"2013","journal-title":"PLoS Pathog"},{"key":"2022020121022986200_DKU566C5","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/jac\/dkr443","article-title":"Isolation of multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR\/L98H mutations in the cyp51A gene in India","volume":"67","author":"Chowdhary","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"2022020121022986200_DKU566C6","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1093\/cid\/cit320","article-title":"Aspergillosis due to voriconazole highly resistant Aspergillus fumigatus and recovery of genetically related resistant isolates from domiciles","volume":"57","author":"van der Linden","year":"2013","journal-title":"Clin Infect Dis"},{"key":"2022020121022986200_DKU566C7","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.3201\/eid1710.110226","article-title":"Clinical implications of azole resistance in Aspergillus fumigatus, the Netherlands, 2007\u20132009","volume":"17","author":"van der Linden","year":"2011","journal-title":"Emerg Infect Dis"},{"key":"2022020121022986200_DKU566C8","doi-asserted-by":"crossref","first-page":"3513","DOI":"10.1128\/AAC.00167-13","article-title":"cyp51A-Based mechanisms of Aspergillus fumigatus azole drug resistance present in clinical samples from Germany","volume":"57","author":"Bader","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"2022020121022986200_DKU566C9","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1097\/QCO.0000000000000005","article-title":"Azole resistance in Aspergillus fumigatus: a growing public health concern","volume":"26","author":"Vermeulen","year":"2013","journal-title":"Curr Opin Infect Dis"},{"key":"2022020121022986200_DKU566C10","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1093\/jac\/dku009","article-title":"Prevalence and molecular characterization of azole resistance in Aspergillus spp. isolates from German cystic fibrosis patients","volume":"69","author":"Fischer","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2022020121022986200_DKU566C11","doi-asserted-by":"crossref","first-page":"pii=20326","DOI":"10.2807\/ese.17.48.20326-en","article-title":"Azole-resistant Aspergillus fumigatus due to TR46\/Y121F\/T289A mutation emerging in Belgium, July 2012","volume":"17","author":"Vermeulen","year":"2012","journal-title":"Euro Surveill"},{"key":"2022020121022986200_DKU566C12","doi-asserted-by":"crossref","first-page":"5096","DOI":"10.1128\/AAC.02855-14","article-title":"First detection of TR46\/Y121F\/T289A and of TR34\/L98H in azole naive patients in Denmark despite negative findings in the environment","volume":"58","author":"Astvad","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"2022020121022986200_DKU566C13","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/jac\/dkt397","article-title":"Azole-resistant Aspergillus fumigatus with the environmental TR46\/Y121F\/T289A mutation in India","volume":"69","author":"Chowdhary","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2022020121022986200_DKU566C14","doi-asserted-by":"crossref","first-page":"e52871","DOI":"10.1371\/journal.pone.0052871","article-title":"Clonal expansion and emergence of environmental multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR34\/L98H mutations in the cyp51A gene in India","volume":"7","author":"Chowdhary","year":"2012","journal-title":"PLoS One"},{"key":"2022020121022986200_DKU566C15","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1086\/588660","article-title":"Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer\/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\/MSG) Consensus Group","volume":"46","author":"De Pauw","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2022020121022986200_DKU566C16","doi-asserted-by":"crossref","first-page":"pii=20262","DOI":"10.2807\/ese.17.36.20262-en","article-title":"Azole-resistant invasive aspergillosis in a patient with acute myeloid leukaemia in Germany","volume":"17","author":"Hamprecht","year":"2012","journal-title":"Euro Surveill"},{"key":"2022020121022986200_DKU566C17","doi-asserted-by":"crossref","first-page":"6060","DOI":"10.1128\/AAC.01017-12","article-title":"First reported case of azole-resistant Aspergillus fumigatus due to the TR\/L98H mutation in Germany","volume":"56","author":"Rath","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"2022020121022986200_DKU566C18","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1128\/JCM.00335-12","article-title":"Molecular epidemiology of Aspergillus fumigatus isolates harboring the TR34\/L98H azole resistance mechanism","volume":"50","author":"Camps","year":"2012","journal-title":"J Clin Microbiol"},{"key":"2022020121022986200_DKU566C19","doi-asserted-by":"crossref","first-page":"832","DOI":"10.3201\/eid1905.130075","article-title":"Azole-resistant Aspergillus fumigatus, Iran","volume":"19","author":"Seyedmousavi","year":"2013","journal-title":"Emerg Infect Dis"},{"key":"2022020121022986200_DKU566C20","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1093\/cid\/cit321","article-title":"Voriconazole resistance in Aspergillus fumigatus: should we be concerned?","volume":"57","author":"Denning","year":"2013","journal-title":"Clin Infect Dis"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/70\/5\/1522\/42355725\/jac_70_5_1522.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/70\/5\/1522\/42355725\/jac_70_5_1522.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T21:15:08Z","timestamp":1643750108000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/70\/5\/1522\/691319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,27]]},"references-count":20,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2015,1,27]]},"published-print":{"date-parts":[[2015,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dku566","relation":{},"ISSN":["1460-2091","0305-7453"],"issn-type":[{"value":"1460-2091","type":"electronic"},{"value":"0305-7453","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,5]]},"published":{"date-parts":[[2015,1,27]]}}}