{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:01:16Z","timestamp":1792789276866,"version":"4.5.0"},"reference-count":93,"publisher":"The Royal Society","issue":"1709","license":[{"start":{"date-parts":[[2016,12,5]],"date-time":"2016-12-05T00:00:00Z","timestamp":1480896000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"name":"Astellas, Basilea and Merck"}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Phil. Trans. R. Soc. B"],"published-print":{"date-parts":[[2016,12,5]]},"abstract":"<jats:p>\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    fungi are the cause of an array of diseases affecting humans, animals and plants. The triazole antifungal agents itraconazole, voriconazole, isavuconazole and posaconazole are treatment options against diseases caused by\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    . However, resistance to azoles has recently emerged as a new therapeutic challenge in six continents. Although de novo azole resistance occurs occasionally in patients during azole therapy, the main burden is the aquisition of resistance through the environment. In this setting, the evolution of resistance is attributed to the widespread use of azole-based fungicides. Although ubiquitously distributed,\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    is not a phytopathogen. However, agricultural fungicides deployed against plant pathogenic moulds such as\n                    <jats:italic>Fusarium<\/jats:italic>\n                    ,\n                    <jats:italic>Mycospaerella<\/jats:italic>\n                    and\n                    <jats:italic>A. flavus<\/jats:italic>\n                    also show activity against\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    in the environment and exposure of non-target fungi is inevitable. Further, similarity in molecule structure between azole fungicides and antifungal drugs results in cross-resistance of\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    to medical azoles. Clinical studies have shown that two-thirds of patients with azole-resistant infections had no previous history of azole therapy and high mortality rates between 50% and 100% are reported in azole-resistant invasive aspergillosis. The resistance phenotype is associated with key mutations in the\n                    <jats:italic>cyp51A<\/jats:italic>\n                    gene, including TR\n                    <jats:sub>34<\/jats:sub>\n                    \/L98H, TR\n                    <jats:sub>53<\/jats:sub>\n                    and TR\n                    <jats:sub>46<\/jats:sub>\n                    \/Y121F\/T289A resistance mechanisms. Early detection of resistance is of paramount importance and if demonstrated, either with susceptibility testing or through molecular analysis, azole monotherapy should be avoided. Liposomal amphotericin B or a combination of voriconazole and an echinocandin are recomended for azole-resistant aspergillosis.\n                  <\/jats:p>\n                  <jats:p>This article is part of the themed issue \u2018Tackling emerging fungal threats to animal health, food security and ecosystem resilience\u2019.<\/jats:p>","DOI":"10.1098\/rstb.2015.0460","type":"journal-article","created":{"date-parts":[[2016,10,24]],"date-time":"2016-10-24T21:18:37Z","timestamp":1477343917000},"page":"20150460","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":293,"title":["Clinical implications of globally emerging azole resistance in\n                    <i>Aspergillus fumigatus<\/i>"],"prefix":"10.1098","volume":"371","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3253-6080","authenticated-orcid":false,"given":"Jacques F.","family":"Meis","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and 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