{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T18:53:27Z","timestamp":1793904807300,"version":"4.8.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Trichophyton indotineae has recently emerged as a major etiological agent of treatment-resistant dermatophytosis, particularly in India and Iran. Resistance to terbinafine is predominantly associated with point mutations in the squalene epoxidase (SQLE) gene. This study investigated the antifungal susceptibility of clinical dermatophyte isolates from Iran and characterized SQLE mutations in terbinafine-resistant strains.<\/jats:p>\n                  <jats:p>Over a 6-month period, 176 clinical dermatophyte isolates comprising 134 T. indotineae and 42 non-indotineae species were collected and identified by internal transcribed spacer (ITS) sequencing. In vitro antifungal susceptibility testing to eight antifungal agents was assessed according to CLSI M38 guidelines. Minimum inhibitory concentration (MIC) ranges, MIC\u2085\u2080, MIC\u2089\u2080, and geometric mean MICs were calculated. SQLE gene sequencing was performed for isolates exhibiting reduced terbinafine susceptibility.<\/jats:p>\n                  <jats:p>Out of 176 dermatophyte isolates, 66 (37.5%) demonstrated terbinafine MICs \u2265 0.5 \u00b5g\/ml. Among these 66 isolates, 64 were T. indotineae (out of 134 total T. indotineae isolates, 47.76%), and 2 were T. tonsurans (out of 21 total T. tonsurans isolates, 9.52%). High-level terbinafine resistance (MIC \u2265 16 \u00b5g\/ml) was observed in 50% (32\/64) of T. indotineae isolates. Among the 66 resistant isolates, only 3 were wild-type: one T. indotineae and two T. tonsurans. The most prevalent SQLE alterations were the double mutation Phe397Leu + Ala448Thr (34.38%) and the single mutation Leu393Ser (32.81%), followed by the 1192 C\u2192A substitution (10.94%). Notably, Ala448Thr also occurred in phenotypically susceptible isolates, yet correlated with increased MICs of itraconazole and voriconazole. Fluconazole showed poor activity (geometric mean MIC: 43.5072 \u00b5g\/ml), whereas posaconazole exhibited the highest in vitro activity. Terbinafine remained effective for non-T. indotineae species, but is ineffective for T. indotineae-associated dermatophytosis due to widespread resistance. None of the isolates identified as T. interdigitale\/mentagrophytes, T. rubrum, Microsporum canis, and Trichophyton benhamiae were resistant to TRB.<\/jats:p>\n                  <jats:p>This multicenter survey reveals high terbinafine resistance in Iranian T. indotineae isolates, linked to SQLE mutations and azole cross-resistance. Routine antifungal susceptibility testing, molecular screening, and alternative therapies are essential, prioritizing non-terbinafine options for T. indotineae (while it remains effective against other dermatophytes). Continued surveillance, accurate species identification, and tailored management are critical to control recalcitrant dermatophytosis.<\/jats:p>","DOI":"10.1093\/mmy\/myag064","type":"journal-article","created":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T11:31:09Z","timestamp":1782041469000},"source":"Crossref","is-referenced-by-count":2,"title":["Multicenter study reveals alarming terbinafine resistance in\n                    <i>Trichophyton indotineae<\/i>\n                    isolates from Iran"],"prefix":"10.1093","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0178-4372","authenticated-orcid":false,"given":"Shima","family":"Aboutalebian","sequence":"first","affiliation":[{"name":"School of Medicine, Isfahan University of Medical Sciences Department of Medical Parasitology and Mycology, , Isfahan 7346181746 ,","place":["Iran"]},{"name":"Mycology Reference Laboratory, Research Core Facilities, Isfahan University of Medical Sciences , Isfahan 7346181746 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Jahanshiri","sequence":"additional","affiliation":[{"name":"Pasteur Institute of Iran Department of Mycology, , Tehran 1316943551 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboobeh","family":"Kharazi","sequence":"additional","affiliation":[{"name":"School of Medicine, Shiraz University of Medical Sciences Department of Medical Mycology and Parasitology, , Shiraz 7134814336 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Reza","family":"Shidfar","sequence":"additional","affiliation":[{"name":"School of Public Health, Tehran University of Medical Sciences Department of Medical Parasitology and Mycology, , Tehran 1416753955 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahla","family":"Shadzi","sequence":"additional","affiliation":[{"name":"School of Medicine, Isfahan University of Medical Sciences Department of Medical Parasitology and Mycology, , Isfahan 7346181746 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Chadeganipour","sequence":"additional","affiliation":[{"name":"School of Medicine, Isfahan University of Medical Sciences Department of Medical Parasitology and Mycology, , Isfahan 7346181746 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahzad","family":"Erami","sequence":"additional","affiliation":[{"name":"School of Medicine, Infectious Diseases Research Center, Kashan University of Medical Sciences Department of Infectious Diseases, , Kashan 8731753153 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4651-5224","authenticated-orcid":false,"given":"Hossein","family":"Mirhendi","sequence":"additional","affiliation":[{"name":"School of Medicine, Isfahan University of Medical Sciences Department of Medical Parasitology and Mycology, , Isfahan 7346181746 ,","place":["Iran"]},{"name":"Mycology Reference Laboratory, Research Core Facilities, Isfahan University of Medical Sciences , Isfahan 7346181746 ,","place":["Iran"]},{"name":"Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences , Isfahan 7346181746 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"issue":"7","key":"2026070810520954200_bib1","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1111\/myc.13091","article-title":"Alarming India-wide phenomenon of antifungal resistance in dermatophytes: a multicentre study","volume":"63","author":"Ebert","year":"2020","journal-title":"Mycoses"},{"issue":"2","key":"2026070810520954200_bib2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3390\/jof3020017","article-title":"Molecular identification and antifungal susceptibility patterns of clinical dermatophytes following CLSI and EUCAST guidelines","volume":"3","author":"Dabas","year":"2017","journal-title":"J Fungi"},{"issue":"1-2","key":"2026070810520954200_bib3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s11046-016-0073-9","article-title":"Toward a novel multilocus phylogenetic taxonomy for the dermatophytes","volume":"182","author":"de\u00a0Hoog","year":"2017","journal-title":"Mycopathologia"},{"issue":"1","key":"2026070810520954200_bib4","doi-asserted-by":"publisher","first-page":"e70013","DOI":"10.1111\/myc.70013","article-title":"Increasing and alarming prevalence of Trichophyton indotineae as the primary causal agent of skin dermatophytosis in Iran","volume":"68","author":"Mirhendi","year":"2025","journal-title":"Mycoses"},{"issue":"4","key":"2026070810520954200_bib5","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1177\/12034754221077891","article-title":"Terbinafine resistant Trichophyton indotineae isolated in patients with superficial dermatophyte infection in Canadian patients","volume":"26","author":"Posso-De\u00a0Los\u00a0Rios","year":"2022","journal-title":"J Cutan Med Surg"},{"issue":"8","key":"2026070810520954200_bib6","first-page":"e00562","article-title":"Terbinafine-resistant dermatophytes and the presence of Trichophyton indotineae in North America","volume":"61","author":"Ca\u00f1ete-Gibas","year":"2023","journal-title":"J Clin Microbiol"},{"issue":"12","key":"2026070810520954200_bib7","doi-asserted-by":"publisher","first-page":"3558","DOI":"10.3390\/jcm13123558","article-title":"Trichophyton indotineae, an emerging drug-resistant dermatophyte: a review of the treatment options","volume":"13","author":"Sonego","year":"2024","journal-title":"J Clin Med"},{"issue":"3","key":"2026070810520954200_bib8","doi-asserted-by":"publisher","first-page":"220","DOI":"10.3390\/jof8030220","article-title":"Terbinafine resistance in dermatophytes: a French multicenter prospective study","volume":"8","author":"Moreno-Sabater","year":"2022","journal-title":"J Fungi"},{"issue":"5","key":"2026070810520954200_bib9","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1093\/jac\/dkaa562","article-title":"In vitro activity of the novel antifungal olorofim against dermatophytes and opportunistic moulds including Penicillium and Talaromyces species","volume":"76","author":"Singh","year":"2021","journal-title":"J Antimicrob Chemother"},{"issue":"7","key":"2026070810520954200_bib10","doi-asserted-by":"crossref","first-page":"757","DOI":"10.3390\/jof8070757","article-title":"Trichophyton indotineae\u2014an emerging pathogen causing recalcitrant dermatophytoses in India and worldwide\u2014a multidimensional perspective","volume":"8","author":"Uhrla\u00df","year":"2022","journal-title":"J Fungi"},{"issue":"1","key":"2026070810520954200_bib11","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41467-018-07928-x","article-title":"Structure and inhibition mechanism of the catalytic domain of human squalene epoxidase","volume":"10","author":"Padyana","year":"2019","journal-title":"Nat Commun"},{"issue":"7","key":"2026070810520954200_bib12","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1128\/aac.00115-17","article-title":"Terbinafine resistance of trichophyton clinical isolates caused by specific point mutations in the squalene epoxidase gene","volume":"61","author":"Yamada","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"2026070810520954200_bib13","doi-asserted-by":"publisher","first-page":"468","DOI":"10.25259\/IJDVL_303_20","article-title":"The unprecedented epidemic-like scenario of dermatophytosis in India: III. Antifungal resistance and treatment options","volume":"87","author":"Verma","year":"2021","journal-title":"Indian Journal of Dermatology, Venereology and Leprology."},{"issue":"3","key":"2026070810520954200_bib14","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1007\/s11046-018-0242-0","article-title":"Resistance mechanism in a terbinafine-resistant strain of microsporum canis","volume":"183","author":"Kano","year":"2018","journal-title":"Mycopathologia"},{"issue":"4","key":"2026070810520954200_bib15","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/mmy\/myaa114","article-title":"A review of recent research on antifungal agents against dermatophyte biofilms","volume":"59","author":"FdO","year":"2021","journal-title":"Med Mycol"},{"issue":"8","key":"2026070810520954200_bib16","doi-asserted-by":"publisher","first-page":"629","DOI":"10.3390\/jof7080629","article-title":"State-of-the-art dermatophyte infections: epidemiology aspects, pathophysiology, and resistance mechanisms","volume":"7","author":"Martinez-Rossi","year":"2021","journal-title":"J Fungi"},{"key":"2026070810520954200_bib17","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.3389\/fmicb.2018.01108","article-title":"Dermatophyte resistance to antifungal drugs: mechanisms and prospectus","volume":"9","author":"Martinez-Rossi","year":"2018","journal-title":"Front Microbiol."},{"issue":"3","key":"2026070810520954200_bib18","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1111\/myc.13202","article-title":"Antifungal susceptibility testing of dermatophytes: development and evaluation of an optimised broth microdilution method","volume":"64","author":"Curatolo","year":"2021","journal-title":"Mycoses"},{"issue":"3","key":"2026070810520954200_bib19","doi-asserted-by":"publisher","first-page":"myad020","DOI":"10.1093\/mmy\/myad020","article-title":"Microbial and clinical epidemiology of invasive fungal rhinosinusitis in hospitalized COVID-19 patients, the divergent causative agents","volume":"61","author":"Erami","year":"2023","journal-title":"Med Mycol"},{"key":"2026070810520954200_bib20","doi-asserted-by":"publisher","first-page":"1113065","DOI":"10.3389\/fimmu.2022.1113065","article-title":"The epidemic of the multiresistant dermatophyte Trichophyton indotineae has reached China","volume":"13","author":"Jia","year":"2023","journal-title":"Front Immunol"},{"issue":"7","key":"2026070810520954200_bib21","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1111\/myc.12772","article-title":"High terbinafine resistance in Trichophyton interdigitale isolates in Delhi, India harbouring mutations in the squalene epoxidase gene","volume":"61","author":"Singh","year":"2018","journal-title":"Mycoses"},{"issue":"8","key":"2026070810520954200_bib22","doi-asserted-by":"publisher","first-page":"myaf071","DOI":"10.1093\/mmy\/myaf071","article-title":"Evaluation of simple molecular methods for distinction of the newly emerging dermatophyte Trichophyton indotineae","volume":"63","author":"Aboutalebian","year":"2025","journal-title":"Med Mycol"},{"issue":"1","key":"2026070810520954200_bib23","doi-asserted-by":"publisher","first-page":"e70015","DOI":"10.1111\/myc.70015","article-title":"Development and evaluation of SYBR green real-time PCR for rapid and specific identification of Trichophyton indotineae","volume":"68","author":"Rouhi","year":"2025","journal-title":"Mycoses"},{"issue":"8","key":"2026070810520954200_bib24","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1128\/aac.00056-21","article-title":"Antifungal susceptibility and mutations in the squalene epoxidase gene in dermatophytes of the trichophyton mentagrophytes species complex","volume":"65","author":"Kong","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"2026070810520954200_bib25","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1128\/aac.01964-19","article-title":"MIC and upper limit of wild-type distribution for 13 antifungal agents against a trichophyton mentagrophytes-trichophyton interdigitale complex of Indian origin","volume":"64","author":"Shaw","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"2026070810520954200_bib26","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3201\/eid2801.210883","article-title":"Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae","volume":"28","author":"Jabet","year":"2022","journal-title":"France Emerg Infect Dis."},{"issue":"10","key":"2026070810520954200_bib27","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1007\/s10096-018-3317-4","article-title":"Antifungal drug susceptibility profile of clinically important dermatophytes and determination of point mutations in terbinafine-resistant isolates","volume":"37","author":"MS-G","year":"2018","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2026070810520954200_bib28","doi-asserted-by":"publisher","first-page":"845","DOI":"10.2147\/IDR.S246025","article-title":"Emergence of terbinafine resistant trichophyton mentagrophytes in Iran, harboring mutations in the squalene epoxidase (SQLE)","volume":"Volume 13","author":"Taghipour","year":"2020","journal-title":"Gene. Infect Drug Resist."},{"issue":"4","key":"2026070810520954200_bib29","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1007\/s11046-024-00855-0","article-title":"High prevalence of terbinafine resistance among trichophyton mentagrophytes\/T. interdigitale species complex, a cross-sectional study from 2021 to 2022 in Northern parts of Iran","volume":"189","author":"Haghani","year":"2024","journal-title":"Mycopathologia"},{"issue":"5","key":"2026070810520954200_bib30","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1111\/myc.12315","article-title":"In vitro susceptibility patterns of clinically important trichophyton and epidermophyton species against nine antifungal drugs","volume":"58","author":"Badali","year":"2015","journal-title":"Mycoses"},{"issue":"7","key":"2026070810520954200_bib31","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1093\/mmy\/myw016","article-title":"In vitro activity of new azoles luliconazole and lanoconazole compared with ten other antifungal drugs against clinical dermatophyte isolates","volume":"54","author":"Baghi","year":"2016","journal-title":"Med Mycol"},{"issue":"5","key":"2026070810520954200_bib32","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1128\/aac.02522-17","article-title":"Mutation in the squalene epoxidase gene of trichophyton interdigitale and trichophyton rubrum associated with allylamine resistance","volume":"62","author":"Rudramurthy","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"2026070810520954200_bib33","doi-asserted-by":"publisher","first-page":"2977","DOI":"10.1128\/JCM.42.7.2977-2979.2004","article-title":"Intra-and interlaboratory study of a method for testing the antifungal susceptibilities of dermatophytes","volume":"42","author":"Ghannoum","year":"2004","journal-title":"J Clin Microbiol"},{"issue":"1","key":"2026070810520954200_bib34","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1111\/bjd.19420","article-title":"Treatment-resistant tinea corporis, a potential public health issue","volume":"184","author":"Chen","year":"2021","journal-title":"Br J Dermatol"},{"issue":"2","key":"2026070810520954200_bib35","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1001\/jamadermatol.2014.2154","article-title":"Posaconazole treatment of extensive skin and nail dermatophytosis due to autosomal recessive deficiency of CARD9","volume":"151","author":"Jachiet","year":"2015","journal-title":"JAMA dermatology"},{"issue":"10","key":"2026070810520954200_bib36","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1128\/aac.01126-19","article-title":"Emerging terbinafine resistance in Trichophyton: clinical characteristics, squalene epoxidase gene mutations, and a reliable EUCAST method for detection","volume":"63","author":"Saunte","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"issue":"6","key":"2026070810520954200_bib37","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s15010-020-01498-1","article-title":"Intrinsic resistance to terbinafine among human and animal isolates of Trichophyton mentagrophytes related to amino acid substitution in the squalene epoxidase","volume":"48","author":"\u0141agowski","year":"2020","journal-title":"Infection"},{"issue":"6","key":"2026070810520954200_bib38","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3390\/jof7060419","article-title":"Molecular epidemiology and antifungal susceptibility of trichophyton isolates in Greece: emergence of terbinafine-resistant trichophytonmentagrophytes type VIII locally and globally","volume":"7","author":"Siopi","year":"2021","journal-title":"J Fungi (Basel)"},{"issue":"1","key":"2026070810520954200_bib39","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/jdv.20810","article-title":"Trichophyton indotineae: epidemiology, antifungal resistance and antifungal stewardship strategies","volume":"40","author":"Gupta","year":"2026","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"issue":"7","key":"2026070810520954200_bib40","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1111\/myc.13091","article-title":"Alarming India-wide phenomenon of antifungal resistance in dermatophytes: a multicentre study","volume":"63","author":"Ebert","year":"2020","journal-title":"Mycoses"}],"container-title":["Medical Mycology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mmy\/advance-article-pdf\/doi\/10.1093\/mmy\/myag064\/68576259\/myag064.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mmy\/article-pdf\/64\/7\/myag064\/68576259\/myag064.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mmy\/article-pdf\/64\/7\/myag064\/68576259\/myag064.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T14:52:14Z","timestamp":1783522334000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mmy\/article\/doi\/10.1093\/mmy\/myag064\/8713293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/mmy\/myag064","relation":{},"ISSN":["1369-3786","1460-2709"],"issn-type":[{"value":"1369-3786","type":"print"},{"value":"1460-2709","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,6,22]]},"article-number":"myag064"}}