{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T07:12:49Z","timestamp":1776582769951,"version":"3.51.2"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T00:00:00Z","timestamp":1737763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Cutaneous fungal infections represent a significant burden worldwide with a high impact on public health. Accurate identification of dermatophyte species causing these infections is vital for an appropriate treatment. Terbinafine is the primary agent against Trichophyton species due to its clinical efficacy; however, cases of elevated minimum inhibitory concentration (MIC) have been reported, raising clinical and epidemiological concerns. Herein, we aimed to detect Trichophyton rubrum and Trichophyton interdigitale isolates collected from clinical samples with terbinafine-high MICs (TRB-hMIC). A total of 168 isolates, recovered from 2017 to 2023, were identified as T. rubrum complex (140\/83.4%) or T. interdigitale (28\/16.7%) and further screened regarding their terbinafine susceptibility. Four isolates with capacity to grow in terbinafine media were detected by screening, and these and a further sixteen random isolates were submitted to the broth microdilution method. This methodology confirmed the four (2.4%) isolates as TRB-hMIC. One T. rubrum and three T. interdigitale showed a minimum inhibitory concentration (MIC) higher than 1 mg\/L. Partial sequencing of the SQLE gene identified point mutations in T. rubrum (Phe397Iso) and in one T. interdigitale (Phe397Leu) isolate. Notably, in the other two T. interdigitale isolates with TRB-hMIC, no point mutations in the SQLE gene were identified. In conclusion, TRB-hMIC isolates (T. rubrum and T. interdigitale) were identified in clinical samples analyzed in Portugal, as antifungal susceptibility testing is a crucial routine for identifying treatment failures and also for epidemiological purposes aiming to monitor the dynamics of terbinafine resistance.<\/jats:p>","DOI":"10.3390\/pathogens14020115","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T03:54:27Z","timestamp":1737950067000},"page":"115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prevalence of T. rubrum and T. interdigitale Exhibiting High MICs to Terbinafine in Clinical Samples Analyzed in the Portuguese Mycology Reference Laboratory"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8979-9343","authenticated-orcid":false,"given":"Helena","family":"Schirmer","sequence":"first","affiliation":[{"name":"Department of Basics Health Sciences, Federal University of Health and Sciences of Porto Alegre (UFCSPA), Porto Alegre 90050-170, Brazil"}]},{"given":"Camila","family":"Henriques","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Influenza and Other Respiratory Virus, National Institute of Health Doutor Ricardo Jorge (INSA), 1649-016 Lisbon, Portugal"}]},{"given":"Helena","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Reference Unit for Parasitic and Fungal Infections, Department of Infectious Diseases, National Institute of Health Doutor Ricardo Jorge (INSA), 1649-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1169-252X","authenticated-orcid":false,"given":"Cristina","family":"Ver\u00edssimo","sequence":"additional","affiliation":[{"name":"Reference Unit for Parasitic and Fungal Infections, Department of Infectious Diseases, National Institute of Health Doutor Ricardo Jorge (INSA), 1649-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6585-7775","authenticated-orcid":false,"given":"Raquel","family":"Sabino","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"Faculdade de Medicina, Instituto de Sa\u00fade Ambiental, Universidade de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Laborat\u00f3rio Associado TERRA\u2014Laborat\u00f3rio para o Uso Sustent\u00e1vel da Terra e dos Servi\u00e7os dos Ecossistemas, Instituto Superior de Agronomia, 1349-017 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. (2017). Global and Multi-National Prevalence of Fungal Diseases\u2014Estimate Precision. J. Fungi., 3.","DOI":"10.3390\/jof3040057"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1111\/jdv.18050","article-title":"Prevalence of most common skin diseases in Europe: A population-based study","volume":"36","author":"Richard","year":"2022","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1093\/cid\/ciy776","article-title":"Estimation of Direct Healthcare Costs of Fungal Diseases in the United States","volume":"68","author":"Benedict","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3390\/jof6040195","article-title":"Belgian National Survey on Tinea Capitis: Epidemiological Considerations and Highlight of Terbinafine-Resistant T. mentagrophytes with a Mutation on SQLE Gene","volume":"6","author":"Sacheli","year":"2020","journal-title":"J. Fungi."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s11046-021-00542-4","article-title":"Epidemiology of Dermatophytes in Belgium: A 5 Years\u2019 Survey","volume":"186","author":"Sacheli","year":"2021","journal-title":"Mycopathologia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1111\/jdv.17241","article-title":"Emerging antifungal treatment failure of dermatophytosis in Europe: Take care or it may become endemic","volume":"35","author":"Saunte","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"800","DOI":"10.25259\/IJDVL_1025_19","article-title":"Etiological prevalence and antifungal sensitivity patterns of dermatophytosis in India\u2014A multicentric study","volume":"87","author":"Tahiliani","year":"2021","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.1468-3083.2012.04584.x","article-title":"Terbinafine in the treatment of dermatophyte toenail onychomycosis: A meta-analysis of efficacy for continuous and intermittent regimens","volume":"27","author":"Gupta","year":"2013","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.jaad.2016.08.061","article-title":"Systemic antifungal therapy for tinea capitis in children: An abridged Cochrane Review","volume":"76","author":"Chen","year":"2016","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1128\/AAC.47.1.82-86.2003","article-title":"Clinical Trichophyton rubrum Strain Exhibiting Primary Resistance to Terbinafine","volume":"47","author":"Mukherjee","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1080\/13693780410001661482","article-title":"Biochemical characterization of terbinafine-resistant Trichophyton rubrum isolates","volume":"42","author":"Favre","year":"2004","journal-title":"Med. Mycol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yamada, T., Maeda, M., Alshahni, M.M., Tanaka, R., Yaguchi, T., Bontems, O., Salamin, K., Fratti, M., and Monod, M. (2017). Terbinafine Resistance of Trichophyton Clinical Isolates Caused by Specific Point Mutations in the Squalene Epoxidase Gene. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.00115-17"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hwang, J.K., Bakotic, W.L., Gold, J.A.W., Magro, C.M., and Lipner, S.R. (2023). Isolation of Terbinafine-Resistant Trichophyton rubrum from Onychomycosis Patients Who Failed Treatment at an Academic Center in New York, United States. J. Fungi, 9.","DOI":"10.3390\/jof9070710"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3201\/eid2801.210883","article-title":"Extensive Dermatophytosis Caused by Terbinafine-Resistant Trichophyton indotineae, France","volume":"28","author":"Jabet","year":"2022","journal-title":"Emerg. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Uhrla\u00df, S., Verma, S.B., Gr\u00e4ser, Y., Rezaei-Matehkolaei, A., Hatami, M., Schaller, M., and Nenoff, P. (2022). Trichophyton indotineae\u2014An Emerging Pathogen Causing Recalcitrant Dermatophytoses in India and Worldwide\u2014A Multidimensional Perspective. J. Fungi., 8.","DOI":"10.3390\/jof8070757"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e0090323","DOI":"10.1128\/jcm.00903-23","article-title":"Trichophyton indotineae and other terbinafine-resistant dermatophytes in North America","volume":"61","year":"2023","journal-title":"J. Clin. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1128\/AAC.01600-05","article-title":"Biological, Biochemical, and Molecular Characterization of a New Clinical Trichophyton rubrum Isolate Resistant to Terbinafine","volume":"50","author":"Osborne","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","unstructured":"The European Committee on Antimicrobial Susceptibility Testing (2024, December 23). Overview of Antifungal ECOFFs and Clinical Breakpoints for Yeasts, Moulds and Dermatophytes Using the EUCAST E.Def 7.4, E.Def 9.4 and E.Def 11.0 Procedures. Version 3. Available online: http:\/\/www.eucast.org."},{"key":"ref_19","unstructured":"Clinical and Laboratory Standards Institute (CLSI) (2017). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi, CLSI. [3rd ed.]. CLSI standard M38 (ISBN 1-56238-830-4 [Print])."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1093\/jac\/dkaa111","article-title":"Multicentre validation of a EUCAST method for the antifungal susceptibility testing of microconidia-forming dermatophytes","volume":"75","author":"Arendrup","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","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":"Salehi","year":"2018","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1111\/jdv.19253","article-title":"Reliable and rapid identification of terbinafine resistance in dermatophytic nail and skin infections","volume":"37","author":"Blanchard","year":"2023","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_23","doi-asserted-by":"crossref","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"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e01126-19","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."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ca\u00f1ete-Gibas, C.F., Mele, J., Patterson, H.P., Sanders, C.J., Ferrer, D., Garcia, V., Fan, H., David, M., and Wiederhold, N.P. (2023). Terbinafine-Resistant Dermatophytes and the Presence of Trichophyton indotineae in North America. J. Clin. Microbiol., 61.","DOI":"10.1128\/jcm.00562-23"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Moreno-Sabater, A., Normand, A.C., Bidaud, A.L., Cremer, G., Foulet, F., Brun, S., Bonnal, C., A\u00eft-Ammar, N., Jabet, A., and Ayachi, A. (2022). Terbinafine Resistance in Dermatophytes: A French Multicenter Prospective Study. J. Fungi., 8.","DOI":"10.3390\/jof8030220"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e02522-17","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."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/1346-8138.14809","article-title":"Terbinafine-resistant strain of Trichophyton interdigitale strain isolated from a tinea pedis patient","volume":"46","author":"Hiruma","year":"2019","journal-title":"J. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e01308-23","DOI":"10.1128\/jcm.01308-23","article-title":"Development of an agar-based screening method for terbinafine, itraconazole, and amorolfine susceptibility testing of Trichophyton spp.","volume":"62","author":"Siopi","year":"2023","journal-title":"JCM"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.1093\/jac\/dkx319","article-title":"Multicentre validation of 4-well azole agar plates as a screening method for detection of clinically relevant azole-resistant Aspergillus fumigatus","volume":"72","author":"Arendrup","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1093\/jac\/dkz154","article-title":"Development and multicentre validation of an agar- based screening method for echinocandin susceptibility testing of Aspergillus species","volume":"74","author":"Meletiadis","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_32","unstructured":"Meletiadis, J., Guinea, J., Arikan-Akdagli, S., Friberg, N., Kahlmeter, G., and The Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European 331 Committee for Antimicrobial Susceptibility Testing (EUCAST) (2022). EUCAST Definitive Document E.Def 10.2: Screening Method for the Detection of Azole and Echinocandin Resistance in Aspergillus Using Antifungal Containing Agar Plates, Exemplified by A. fumigatus, EUCAST."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/2\/115\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:36:13Z","timestamp":1759919773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/2\/115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,25]]},"references-count":32,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["pathogens14020115"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14020115","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,25]]}}}