{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:31:43Z","timestamp":1790685103146,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,12,6]],"date-time":"2020-12-06T00:00:00Z","timestamp":1607212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo de Investigaci\u00f3n Sanitaria","award":["PI18\/01155"],"award-info":[{"award-number":["PI18\/01155"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Azole resistance poses a problem for the management of patients with invasive aspergillosis. Former species are in fact groups of closely related species (or complexes); cryptic species frequently show high antifungal resistance. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) Definitive Document (E.Def) 9.3.2 includes guidelines for antifungal susceptibility testing on Aspergillus spp. and clinical breakpoints for amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole against A. flavus, A. fumigatus, A. nidulans, A. niger, and A. terreus. New clinical breakpoints were released in February 2020 and one of the most relevant modifications was the definition of the new \u201csusceptible, increased exposure\u201d (formerly \u201cintermediate\u201d) category. Another relevant change was the adoption of the concept of area of technical uncertainty (ATU) that refers to problematic areas which involve uncertainty of susceptibility categorisation (e.g., when minimum inhibitory concentrations (MICs) for susceptible and resistant organisms overlap). To accommodate both the new \u201csusceptible, increased exposure\u201d category and the concept of ATU, MICs of azoles and amphotericin B that fall in the former \u201cintermediate\u201d category have been automatically categorized as either R (amphotericin B) or ATU (triazoles). Finally, EUCAST-AFST (Antifungal Susceptibility Testing) decided to adopt new breakpoints for less common species provided that the epidemiological cut-off value (ECOFF) is below or comparable to the breakpoint for the type species (A. fumigatus).<\/jats:p>","DOI":"10.3390\/jof6040343","type":"journal-article","created":{"date-parts":[[2020,12,6]],"date-time":"2020-12-06T22:27:12Z","timestamp":1607293632000},"page":"343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Updated EUCAST Clinical Breakpoints against Aspergillus, Implications for the Clinical Microbiology Laboratory"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7901-8355","authenticated-orcid":false,"given":"Jes\u00fas","family":"Guinea","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n, C\/ Dr. Esquerdo, 46, 28007 Madrid, Spain"},{"name":"CIBER Enfermedades Respiratorias-CIBERES (CB06\/06\/0058), Madrid, Spain"},{"name":"Servicio de Microbiolog\u00eda Cl\u00ednica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, C\/ Dr. Esquerdo, 46, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1136\/thoraxjnl-2014-206291","article-title":"The clinical spectrum of pulmonary aspergillosis","volume":"70","author":"Kosmidis","year":"2014","journal-title":"Thorax"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1093\/jac\/dkx527","article-title":"Epidemiology of invasive aspergillosis and triazole-resistant Aspergillus fumigatus in patients with haematological malignancies: A single-centre retrospective cohort study","volume":"73","author":"Lestrade","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.cmi.2018.01.028","article-title":"Invasive aspergillosis with pulmonary and central nervous system involvement during ibrutinib therapy for relapsed chronic lymphocytic leukaemia: Case report","volume":"24","author":"Peri","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_4","first-page":"870","article-title":"Faculty Opinions recommendation of Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: Incidence, risk factors, and outcome","volume":"16","author":"Wanner","year":"2011","journal-title":"Fac. Opin. Post Publ. Peer Rev. Biomed. Lit."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/cid\/ciz391","article-title":"Influenza Coinfection: Be(a)ware of Invasive Aspergillosis","volume":"70","author":"Verweij","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Helleberg, M., Steensen, M., and Arendrup, M.C. (2020). Invasive aspergillosis in patients with severe COVID-19 pneumonia. Clin. Microbiol. Infect.","DOI":"10.1016\/j.cmi.2020.07.047"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.cmi.2018.01.002","article-title":"Diagnosis and management of Aspergillus diseases: Executive summary of the 2017 ESCMID-ECMM-ERS guideline","volume":"24","author":"Ullmann","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/cid\/ciw444","article-title":"Executive Summary: Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America","volume":"63","author":"Patterson","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s11046-014-9775-z","article-title":"Antifungal Susceptibility Profile of Cryptic Species of Aspergillus","volume":"178","year":"2014","journal-title":"Mycopathologia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.simyco.2020.05.002","article-title":"Classification of Aspergillus, Penicillium, Talaromyces and related genera (Eurotiales): An overview of families, genera, subgenera, sections, series and species","volume":"95","author":"Houbraken","year":"2020","journal-title":"Stud. Mycol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3380","DOI":"10.1128\/AAC.00383-13","article-title":"Population-Based Survey of Filamentous Fungi and Antifungal Resistance in Spain (FILPOP Study)","volume":"57","author":"Mellado","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","first-page":"00358-18","article-title":"Molecular Identification and Susceptibility Testing of Molds Isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 Study)","volume":"62","author":"Ayats","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","unstructured":"Escribano, P., Rodr\u00edguez-S\u00e1nchez, B., D\u00edaz-Garc\u00eda, J., Mart\u00edn-G\u00f3mez, M.T., Ib\u00e1\u00f1ez-Mart\u00ednez, E., Rodr\u00edguez-Mayo, M., Pel\u00e1ez, T., De La Pedrosa, E.G.-G., Tejero-Garc\u00eda, R., and Marim\u00f3n, J.M. (2020). Azole resistance survey on clinical Aspergillus fumigatus isolates in Spain. Clin. Microbiol. Infect., in press."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e383","DOI":"10.1016\/S1473-3099(17)30316-X","article-title":"The global problem of antifungal resistance: Prevalence, mechanisms, and management","volume":"17","author":"Perlin","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S82","DOI":"10.3109\/13693786.2010.499916","article-title":"Aspergillus species intrinsically resistant to antifungal agents","volume":"49","author":"Warris","year":"2011","journal-title":"Med. Mycol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrmicro1179","article-title":"Evolution of antifungal-drug resistance: Mechanisms and pathogen fitness","volume":"3","author":"Anderson","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.3201\/eid2106.140717","article-title":"Prospective Multicenter International Surveillance of Azole Resistance in Aspergillus fumigatus","volume":"21","author":"Arendrup","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/cid\/civ885","article-title":"Azole Resistance in Aspergillus fumigatus: Can We Retain the Clinical Use of Mold-Active Antifungal Azoles?","volume":"62","author":"Verweij","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.cmi.2018.11.027","article-title":"Triazole resistance in Aspergillus fumigatus: Recent insights and challenges for patient management","volume":"25","author":"Lestrade","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rivero-Menendez, O., Alastruey-Izquierdo, A., Mellado, E., and Cuenca-Estrella, M. (2016). Triazole Resistance in Aspergillus spp.: A Worldwide Problem?. J. Fungi, 2.","DOI":"10.3390\/jof2030021"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s40265-017-0714-4","article-title":"Triazole Resistance in Aspergillus Species: An Emerging Problem","volume":"77","author":"Mellado","year":"2017","journal-title":"Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105807","DOI":"10.1016\/j.ijantimicag.2019.09.011","article-title":"Azole resistance mechanisms in Aspergillus: Update and recent advances","volume":"55","author":"Capilla","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s11908-019-0702-9","article-title":"Antifungal Resistance: A Concerning Trend for the Present and Future","volume":"21","author":"Hendrickson","year":"2019","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_24","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":"Snelders","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1093\/jac\/dkw323","article-title":"PCR-based detection of Aspergillus fumigatus Cyp51A mutations on bronchoalveolar lavage: A multicentre validation of the AsperGenius assay\u00ae in 201 patients with haematological disease suspected for invasive aspergillosis","volume":"71","author":"Chong","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1093\/cid\/ciy859","article-title":"Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study","volume":"68","author":"Lestrade","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.drup.2015.08.001","article-title":"International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus","volume":"21\u201322","author":"Verweij","year":"2015","journal-title":"Drug Resist. Updat."},{"key":"ref_28","unstructured":"(2020, December 04). European Committee on Antimicrobial Susceptibility Testing, Antifungal Susceptibility Testing. Available online: https:\/\/www.eucast.org\/ast_of_fungi\/."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.cmi.2018.09.008","article-title":"How to: EUCAST recommendations on the screening procedure E.Def 10.1 for the detection of azole resistance in Aspergillus fumigatus isolates using four-well azole-containing agar plates","volume":"25","author":"Guinea","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_30","unstructured":"Arendrup, M., Hope, W., and Howard, S. (2020, December 04). EUCAST Definitive Document E.Def 9.2 Method for the Determination of Broth Dilution Minimum Inhibitory Concentrations of Antifungal Agents for Conidia Forming Moulds. Available online: https:\/\/www.eucast.org\/ast_of_fungi\/."},{"key":"ref_31","unstructured":"The European Committee on Antimicrobial Susceptibility Testing (2020, December 04). Routine and Extended Internal Quality Control for MIC Determination and Agar Dilution for Yeasts, Moulds and Dermatophytes as Recommended by EUCAST. Available online: https:\/\/www.eucast.org\/ast_of_fungi\/."},{"key":"ref_32","first-page":"01693-20","article-title":"Azole and amphotericin B minimum inhibitory concentrations against Aspergillus fumigatus: High agreement between spectrophotometric and visual readings using the EUCAST 9.3.2 procedure","volume":"65","author":"Fajardo","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1016\/j.cmi.2020.06.007","article-title":"How to interpret MICs of antifungal compounds according to the revised clinical breakpoints v. 10.0 European committee on antimicrobial susceptibility testing (EUCAST)","volume":"26","author":"Arendrup","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_34","first-page":"00865-19","article-title":"Molecular Identification, Antifungal Susceptibility Testing, and Mechanisms of Azole Resistance in Aspergillus Species Received within a Surveillance Program on Antifungal Resistance in Spain","volume":"63","author":"Medina","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1093\/jac\/dkaa212","article-title":"Revision of EUCAST breakpoints: Consequences for susceptibility of contemporary Danish mould isolates to isavuconazole and comparators","volume":"75","author":"Guinea","year":"2020","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/6\/4\/343\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:41:39Z","timestamp":1760179299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/6\/4\/343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,6]]},"references-count":35,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["jof6040343"],"URL":"https:\/\/doi.org\/10.3390\/jof6040343","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,6]]}}}