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This multicenter study analyzed 550 clinical\n Aspergillus<\/jats:italic>\n isolates collected in Taiwan from 2021 to 2023, primarily from the respiratory tract (69.6%) and ear (12.9%). Calmodulin-based sequencing identified 24 species across six\n Aspergillus<\/jats:italic>\n sections:\n Flavi<\/jats:italic>\n (28.7%),\n Fumigati<\/jats:italic>\n (28.5%),\n Nigri<\/jats:italic>\n (21.6%),\n Terrei<\/jats:italic>\n (15.8%),\n Nidulantes<\/jats:italic>\n (5.1%), and\n Circumdati<\/jats:italic>\n (0.2%). The major sections were represented by\n Aspergillus fumigatus<\/jats:italic>\n (99.4%),\n Aspergillus flavus<\/jats:italic>\n (91.8%), and\n Aspergillus terreus<\/jats:italic>\n (100%), while section\n Nigri<\/jats:italic>\n comprised nine species, with\n Aspergillus welwitschiae<\/jats:italic>\n (57.1%) predominant. Using Clinical Laboratory Standards Institute (CLSI) M38-A3 protocols, reduced susceptibility to amphotericin B (MIC > 1 \u00b5g\/mL) was observed in\n A. flavus<\/jats:italic>\n (8.3%),\n A. terreus<\/jats:italic>\n (22.7%), and section\n Nidulantes<\/jats:italic>\n (32.1%). Acquired voriconazole resistance was found in 5.8% (9\/156) of\n A. fumigatus<\/jats:italic>\n isolates, including eight with\n cyp51A<\/jats:italic>\n mutations (3 TR\n 34<\/jats:sub>\n \/L98H, 4 TR\n 34<\/jats:sub>\n \/L98H\/S297T\/F495I, and 1 TR\n 46<\/jats:sub>\n \/Y121F\/T289A). Voriconazole non-wild-type phenotypes were identified in 2.1% (3\/158) of\n A. flavus<\/jats:italic>\n isolates, including one carrying a novel P214L mutation (orthologous to\n A. fumigatus<\/jats:italic>\n P216L). Members of the\n Aspergillus niger<\/jats:italic>\n clade exhibited reduced susceptibility to itraconazole and isavuconazole. Anidulafungin, along with novel antifungals including orolofim, manogepix, and rezafungin, demonstrated broad activity across\n Aspergillus<\/jats:italic>\n species, including those with intrinsic or acquired azole resistance. Ibrexafungerp also showed efficacy against azole-resistant\n A. fumigatus<\/jats:italic>\n and\n A. flavus<\/jats:italic>\n . In contrast, opelconazole exhibited limited activity against\n A. flavus<\/jats:italic>\n , the\n A. niger<\/jats:italic>\n clade,\n Aspergillus sydowii<\/jats:italic>\n , and voriconazole-resistant\n A. fumigatus<\/jats:italic>\n . These findings underscore the need for species-level identification, susceptibility testing of causative isolates, and continued surveillance to detect emerging resistance and support the use of novel non-azole antifungals for azole-resistant aspergillosis.\n <\/jats:p>\n <\/jats:sec>\n \n IMPORTANCE<\/jats:title>\n \n Timely and effective antifungal therapy is essential for aspergillosis. This multicenter surveillance study provides comprehensive insights into the species distribution and antifungal susceptibility of 550 clinical\n Aspergillus<\/jats:italic>\n isolates in Taiwan, with intrinsic reduced susceptibility to amphotericin B, itraconazole, or isavuconazole noted in certain species. Regarding acquired resistance, a novel cyp51A mutation, P214L, was identified in an azole-resistant\n Aspergillus flavus<\/jats:italic>\n , orthologous to\n Aspergillus fumigatus<\/jats:italic>\n P216L. Recovery of azole-resistant\n A. fumigatus<\/jats:italic>\n harboring TR34\/L98H or TR46\/Y121F\/T289A mutations remains a concern and emphasizes the need for antifungal stewardship in the environment. Novel antifungals, including orolofim, manogepix, rezafungin, and ibrexafungerp, demonstrated broad activity across\n Aspergillus<\/jats:italic>\n species, including resistant isolates. Nevertheless, the inhaled agent opelconazole exhibited limited activity against\n A. flavus<\/jats:italic>\n regardless of voriconazole susceptibility and against other species showing reduced susceptibility to itraconazole. These findings highlight the importance of species-level identification, susceptibility testing, and continued surveillance and support the use of novel antifungals for aspergillosis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/spectrum.02659-25","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T13:05:30Z","timestamp":1776776730000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Multicenter surveillance of antifungal susceptibility of clinical\n Aspergillus<\/i>\n isolates to conventional and novel antifungal agents in Taiwan, 2021\u20132023"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4769-3938","authenticated-orcid":true,"given":"Ming-I","family":"Hsieh","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r6fpx29","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4317-0048","authenticated-orcid":true,"given":"Pui-Ching","family":"Choi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r6fpx29","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4020-5812","authenticated-orcid":true,"given":"Wan-Lin","family":"Wu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r6fpx29","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9335-8815","authenticated-orcid":true,"given":"Yu-Fu","family":"Lin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r6fpx29","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9607-9088","authenticated-orcid":true,"given":"Chi-Jung","family":"Wu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r6fpx29","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes","place":["Tainan, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/01b8kcc49","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.simyco.2021.100115"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2018.01.002"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2015.08.001"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01611-0"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/myc.13593"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00329-12"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.simyco.2014.07.004"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlae138"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.simyco.2020.05.002"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2604.190840"},{"key":"e_1_3_5_12_2","series-title":"CLSI Standard M38","volume-title":"Reference method for broth dilution antifungal susceptibility testing of filamentous fungi","author":"CLSI","year":"2017","unstructured":"CLSI. 2017. 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