{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:29:01Z","timestamp":1789172941864,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:00:00Z","timestamp":1683158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Numerous reports of resistance to terbinafine in<jats:italic>Trichophyton<\/jats:italic>spp. from all over the world are arousing justified attention and concern. Point mutations in the gene that encodes the squalene epoxidase (SQLE) enzyme are responsible for these therapeutic resistances.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Primary objective of the study was to describe first isolates of<jats:italic>Trichophyton<\/jats:italic>spp. resistant to terbinafine among the patients treated between September 2019 and June 2022 at the Dermatology Units of Ospedale Maggiore Policlinico and San Bortolo Hospital. Secondary objective was to study the resistance mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with confirmed<jats:italic>Trichophyton<\/jats:italic>spp. infection has been treated with systemic and topical terbinafine. Patients were then re\u2010evaluated 12\u2009weeks after the therapy. Patients with incomplete or absent response to terbinafine underwent a new skin scraping for direct mycological examination, new identification of dermatophyte species from culture and MALDI\u2010TOF, molecular species identification, antifungal susceptibility testing and molecular analysis of SQLE gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified five patients without clinical response to treatment with terbinafine. The DNA sequencing of the ITS region identified one<jats:italic>Trichophyton rubrum<\/jats:italic>and four<jats:italic>Trichophyton indotineae<\/jats:italic>. The<jats:italic>T. rubrum<\/jats:italic>strain showed minimum inhibitory concentration (MIC) (90% growth inhibition) of 4\u2009mg\/L for terbinafine. The four<jats:italic>T. indotineae<\/jats:italic>strains showed a MICs range of 0.25\u20134\u2009mg\/L for terbinafine. The analysis of the SQLE gene in the<jats:italic>T. rubrum<\/jats:italic>strain showed a nucleotide substitution generating a missense mutation (L393F). The SQLE gene sequencing in the<jats:italic>T. indotineae<\/jats:italic>strains showed a nucleotide substitution generating a missense mutation (F397L) in two strains, a nucleotide substitution L393S in one strain and a nucleotide substitution F415C in another strain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We report the first cases of terbinafine\u2010resistant<jats:italic>Trichophyton<\/jats:italic>isolates in the Italian population. Solid antifungal management programs will be needed to promote more responsible use of antimycotics and preserve their therapeutic efficacy to control antifungal resistance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/myc.13597","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T10:38:04Z","timestamp":1683196684000},"page":"680-687","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Report of terbinafine resistant<i>Trichophyton<\/i>spp. in Italy: Clinical presentations, molecular identification, antifungal susceptibility testing and mutations in the squalene epoxidase gene"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0586-0136","authenticated-orcid":false,"given":"P.","family":"Bortoluzzi","sequence":"first","affiliation":[{"name":"Dermatology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Prigitano","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche per la Salute Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Sechi","sequence":"additional","affiliation":[{"name":"Dermatology Unit San Bortolo Hospital Vicenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Boneschi","sequence":"additional","affiliation":[{"name":"Dermatology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Germiniasi","sequence":"additional","affiliation":[{"name":"Dermatology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"Esposto","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche per la Salute Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Roman\u00f2","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche per la Salute Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Pavan","sequence":"additional","affiliation":[{"name":"Department of Microbiology San Bortolo Hospital Vicenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Matinato","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche per la Salute Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1457-776X","authenticated-orcid":false,"given":"S.","family":"Veraldi","sequence":"additional","affiliation":[{"name":"Dermatology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"},{"name":"Dipartimento di Scienze Biomediche per la Salute Universit\u00e0 degli Studi di Milano Milan Italy"},{"name":"Dermatology Unit San Bortolo Hospital Vicenza Italy"},{"name":"Department of Microbiology San Bortolo Hospital Vicenza Italy"},{"name":"Department of Pathophysiology and Transplantation Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. V.","family":"Marzano","sequence":"additional","affiliation":[{"name":"Dermatology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"},{"name":"Dipartimento di Scienze Biomediche per la Salute Universit\u00e0 degli Studi di Milano Milan Italy"},{"name":"Dermatology Unit San Bortolo Hospital Vicenza Italy"},{"name":"Department of Microbiology San Bortolo Hospital Vicenza Italy"},{"name":"Department of Pathophysiology and Transplantation Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Grancini","sequence":"additional","affiliation":[{"name":"Laboratorio Analisi \u2013 Laboratorio di Batteriologia, Parassitologia e Micologia Fondazione IRCCS O. Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.2008.01606.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.17241"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/13693780601009493"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00115-17"},{"issue":"3","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.4103\/ijd.IJD_206_17","article-title":"The great Indian epidemic of superficial dermatophytosis: an appraisal","volume":"62","author":"Verma S","year":"2017","journal-title":"Indian J Dermatol"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11046-020-00455-8"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-020-01498-1"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof8030220"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof7110983"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof6040207"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01126-19"},{"key":"e_1_2_10_13_1","first-page":"315","volume-title":"PCR Protocols: A Guide to Methods and Applications","author":"White TJ","year":"1990"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2020.08.042"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-018-3317-4"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof8020150"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa111"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01964-19"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.1.82-86.2003"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00105-019-4431-7"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2801.210883"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof6040195"},{"issue":"95","key":"e_1_2_10_23_1","first-page":"P039","article-title":"Terbinafine resistant Trichophyton mentagrophytes genotype VIII, Indian type, isolated in Finland","volume":"5","author":"J\u00e4rv H","year":"2019","journal-title":"J Fungi"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof7060419"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/myc.12878"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00056-21"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11046-018-0242-0"}],"container-title":["Mycoses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/myc.13597","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T19:49:03Z","timestamp":1729367343000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/myc.13597"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,4]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1111\/myc.13597"],"URL":"https:\/\/doi.org\/10.1111\/myc.13597","archive":["Portico"],"relation":{},"ISSN":["0933-7407","1439-0507"],"issn-type":[{"value":"0933-7407","type":"print"},{"value":"1439-0507","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,4]]},"assertion":[{"value":"2023-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}