{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:49:25Z","timestamp":1793746165729,"version":"4.6.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T00:00:00Z","timestamp":1647302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Interest in aspergillosis has increased over the past decades. An increase in the incidence of azole-resistant Aspergillus fumigatus strains has been reported; therefore, the need for novel therapeutic approaches is urgent. The formation of biofilms contributes to pathogen resistance. We investigated the biofilm formation capabilities of azole-resistant A. fumigatus and analysed the susceptibility of biofilms at various developmental stages to three antifungal agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Biofilm formation of 19 clinical A. fumigatus strains (3 azole-susceptible and 16 azole-resistant strains) was determined by crystal violet staining and by an XTT assay over a period of 48\u2005h. We measured antibiofilm activity of voriconazole, amphotericin B and olorofim. These agents were added before adhesion, after adhesion, after germination and to mature fungal biofilm. Antibiofilm activity was assessed in an XTT assay and in confocal laser scan microscopy. Additionally, a growth\u2013kinetic assay with planktonic A. fumigatus was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Each of the antifungal agents inhibited the metabolic activity of A. fumigatus biofilms when applied at early stages of biofilm formation. The mature biofilms were more resistant. Olorofim and voriconazole showed promising effects against A. fumigatus adhesion and germination, whereas the mature biofilm was not affected by treatment. In contrast, the biofilm of A. fumigatus showed amphotericin B susceptibility throughout the entire developmental process. The planktonic cells were susceptible to all three antifungal drug classes with an inhibition peak at 12\u2005h after incubation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This is the first known study to demonstrate the antibiofilm activity of olorofim, voriconazole and amphotericin B against azole-resistant A. fumigatus.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkac062","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T15:10:10Z","timestamp":1645197010000},"page":"1645-1654","source":"Crossref","is-referenced-by-count":29,"title":["Inhibition of azole-resistant\n                    <i>Aspergillus fumigatus<\/i>\n                    biofilm at various formation stages by antifungal drugs, including olorofim"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2015-275X","authenticated-orcid":false,"given":"Lisa","family":"Kirchhoff","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen , Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Dittmer","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen , Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan-Tiberiu","family":"Furnica","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen , Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Buer","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen , Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eike","family":"Steinmann","sequence":"additional","affiliation":[{"name":"Molecular and Medical Virology, Ruhr University Bochum , Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter-Michael","family":"Rath","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen , Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Steinmann","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen , Essen, Germany"},{"name":"Institute of Clinical Hygiene, Medical Microbiology and Infectiology, Klinikum N\u00fcrnberg, Paracelsus Medical University , Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,15]]},"reference":[{"key":"2022053122483784800_dkac062-B1","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.284.5418.1318","article-title":"Bacterial biofilms: a common cause of persistent infections","volume":"284","author":"Costerton","year":"1999","journal-title":"Science"},{"key":"2022053122483784800_dkac062-B2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13756-019-0533-3","article-title":"Antibiotics versus biofilm: an emerging battleground in microbial communities","volume":"8","author":"Sharma","year":"2019","journal-title":"Antimicrob Resist Infect Control"},{"key":"2022053122483784800_dkac062-B3","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1099\/mic.0.000651","article-title":"Microbe profile: Aspergillus fumigatus: a saprotrophic and opportunistic fungal 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