{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:05:13Z","timestamp":1790298313513,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fungal infections are the most frequent dermatoses. The gold standard treatment for dermatophytosis is the squalene epoxidase (SQLE) inhibitor terbinafine. Pathogenic dermatophytes resistant to terbinafine are an emerging global threat. Here, we determine the proportion of resistant fungal skin infections, analyse the molecular mechanisms of terbinafine resistance, and validate a method for its reliable rapid identification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Between 2013 and 2021, we screened 5634 consecutively isolated\n                      <jats:italic>Trichophyton<\/jats:italic>\n                      for antifungal resistance determined by hyphal growth on Sabouraud dextrose agar medium containing 0.2\u2009\u03bcg\/mL terbinafine. All\n                      <jats:italic>Trichophyton<\/jats:italic>\n                      isolates with preserved growth capacity in the presence of terbinafine underwent\n                      <jats:italic>SQLE<\/jats:italic>\n                      sequencing. Minimum inhibitory concentrations (MICs) were determined by the broth microdilution method.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Over an 8\u2010year period, the proportion of fungal skin infections resistant to terbinafine increased from 0.63% in 2013 to 1.3% in 2021. Our routine phenotypic in vitro screening analysis identified 0.83% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200947\/5634) of\n                      <jats:italic>Trichophyton<\/jats:italic>\n                      strains with in vitro terbinafine resistance. Molecular screening detected a mutation in the\n                      <jats:italic>SQLE<\/jats:italic>\n                      in all cases. Mutations L393F, L393S, F397L, F397I, F397V, Q408K, F415I, F415S, F415V, H440Y, or A\n                      <jats:sub>398<\/jats:sub>\n                      A\n                      <jats:sub>399<\/jats:sub>\n                      G\n                      <jats:sub>400<\/jats:sub>\n                      deletion were detected in\n                      <jats:italic>Trichophyton rubrum.<\/jats:italic>\n                      Mutations L393F and F397L were the most frequent. In contrast, all mutations detected in\n                      <jats:italic>T. mentagrophytes\/T. interdigitale<\/jats:italic>\n                      complex strains were F397L, except for one strain with L393S. All 47 strains featured significantly higher MICs than terbinafine\u2010sensitive controls. The mutation\u2010related range of MICs varied between 0.004 and 16.0\u2009\u03bcg\/mL, with MIC as low as 0.015\u2009\u03bcg\/mL conferring clinical resistance to standard terbinafine dosing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Based on our data, we propose MIC of 0.015\u2009\u03bcg\/mL as a minimum breakpoint for predicting clinically relevant terbinafine treatment failure to standard oral dosing for dermatophyte infections. We further propose growth on Sabouraud dextrose agar medium containing 0.2\u2009\u03bcg\/mL terbinafine and\n                      <jats:italic>SQLE<\/jats:italic>\n                      sequencing as fungal sporulation\u2010independent methods for rapid and reliable detection of terbinafine resistance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdv.19253","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T13:19:41Z","timestamp":1686835181000},"page":"2080-2089","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Reliable and rapid identification of terbinafine resistance in dermatophytic nail and skin infections"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7020-0751","authenticated-orcid":false,"given":"Gabriela","family":"Blanchard","sequence":"first","affiliation":[{"name":"Department of Dermatology 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