{"id":371900,"date":"2024-01-09T14:00:00","date_gmt":"2024-01-09T13:00:00","guid":{"rendered":"https:\/\/medizinonline.com\/?p=371900"},"modified":"2024-01-09T14:02:29","modified_gmt":"2024-01-09T13:02:29","slug":"new-findings-on-terbinafine-resistant-dermatophytes","status":"publish","type":"post","link":"https:\/\/medizinonline.com\/en\/new-findings-on-terbinafine-resistant-dermatophytes\/","title":{"rendered":"New findings on terbinafine-resistant dermatophytes"},"content":{"rendered":"\n

Terbinafine is considered the gold standard in the treatment of dermatophytosis, but pathogenic dermatophytes that are resistant to terbinafine pose a new threat. A Swiss research team involving the Department of Dermatology at Lausanne University Hospital (CHUV) conducted a study to determine the proportion of resistant skin fungi, analyze the molecular mechanisms of terbinafine resistance and validate a method for reliable and rapid identification.<\/strong><\/p>\n\n\n\n

Fungal skin infections are among the most common dermatoses [1]. Dermatophytoses associated with Trichophyton rubrum (T. rubrum)<\/em> and\/or Trichophyton<\/em> interdigitale (T. interdigitale) <\/em>are the most common reason for seeking dermatological treatment [2]. Terbinafine is the drug of choice for dermatophyte infections [3]. Documented terbinafine resistance in T. rubrum<\/em> was first reported in 2003 [4]. Resistance in a T. rubrum strain<\/em> was found to be caused by a missense single point mutation in the squalene epoxidase (SQLE) gene leading to an amino acid substitution, L393F, [5,6]. Since then, cases of terbinafine-resistant Trichophyton strains have become more frequent and there have been several reports, including from Switzerland and Germany [1]. <\/p>\n

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\"\"<\/a><\/figure>\n<\/div>\n

Methodology <\/h3>\n\n

From 2013 to 2021, samples were collected from patients with suspected dermatophyte infections and analyzed mycologically [1]. For this study, all isolated strains of Trichophyton rubrum<\/em> and the complex T. mentagrophytes\/T. interdigital<\/em> considered. Dermatophytes were identified as pathogenic fungi in 15.6% of the 41,513 dermatological samples. The researchers examined a total of 5634 isolated Trichophyton strains (4229 T. rubrum,<\/em> 1405 T. mentagrophytes\/T. interdigital<\/em>) for their antifungal resistance. The latter was determined by hyphal growth on Sabouraud-Dextros agar medium with 0.2 \u03bcg\/ml terbinafine. All trichophyte isolates whose growth ability was maintained in the presence of terbinafine were subjected to SQLE sequencing. The minimum inhibitory concentrations (MIC) were determined by microdilution. <\/p>\n\n

Results of the analysis at a glance <\/h3>\n\n

Over a period of 8 years, the proportion of fungal skin infections that were resistant to terbinafine increased from 0.63% in 2013 to 1.3% in 2021 [1]. Routine phenotypic in vitro screening analysis identified 0.83% (n=47\/5634) of trichophyte strains with in vitro terbinafine resistance. Molecular screening revealed a mutation in the SQLE in all cases. The mutations L393F, L393S, F397L, F397I, F397V, Q408K, F415I, F415S, F415V, H440Y or the deletion A398A399G400 were detected in T. rubrum <\/em>. The mutations L393F and F397L were the most frequent. <\/p>\n\n

In contrast, in the strains of the T. mentagrophytes\/ T. interdigitale complex<\/em> examined, all mutations corresponded to F397L, except for one strain with L393S. All 47 strains had significantly higher minimum inhibitory concentrations (MIC) than the terbinafine-sensitive controls. The mutation-related MIC range was between 0.004 and 16.0 \u03bcg\/ml, whereby an MIC of only 0.015 \u03bcg\/ml already resulted in clinical resistance to the standard terbinafine dosage. <\/p>\n\n

Conclusion <\/h3>\n\n

Based on the available data, the authors suggest an MIC of 0.015 \u03bcg\/ml as the minimum limit for predicting clinically relevant failure of terbinafine treatment after standard oral dosing in dermatophyte infection [1]. Furthermore, they recommend growth on Sabouraud dextrose agar medium with 0.2 \u03bcg\/ml terbinafine and SQLE sequencing as fungal spore-independent methods [1]. <\/p>\n\n

Literature: <\/p>\n\n

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  1. Blanchard G, et al: Reliable and rapid identification of terbinafine resistance in dermatophytic nail and skin infections. J Eur Acad Dermatol Venereol 2023; 37(10): 2080-2089. <\/li>\n\n\n\n
  2. Hay RJ, et al: The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol 2014; 134(6): 1527-1534.<\/li>\n\n\n\n
  3. Gupta AK, et al: Terbinafine in the treatment of dermatophyte toenail onychomycosis: a meta-analysis of efficacy for continuous and intermittent regimens. J Eur Acad Dermatol Venereol 2013; 27(3): 267-272.<\/li>\n\n\n\n
  4. Mukherjee PK, et al: Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine. Antimicrob Agents Chemother 2003; 47(1): 82-86.<\/li>\n\n\n\n
  5. Osborne CS, et al: Amino acid substitution in Trichophyton rubrum squalene epoxidase associated with resistance to terbinafine. Antimicrob Agents Chemother 2005; 49(7): 2840-2844.<\/li>\n\n\n\n
  6. Osborne CS, et al: Biological, biochemical, and molecular characterization of a new clinical Trichophyton rubrum isolate resistant to terbinafine. Antimicrob Agents Chemother 2006; 50(6): 2234-2236.<\/li>\n\n\n\n
  7. Castellanos J, et al: Unusual Inflammatory Tinea Infections: Majocchi’s Granuloma and Deep\/Systemic Dermatophytosis. J Fungi 2021, 7, 929.www.mdpi.com\/2309-608X\/7\/11\/929,<\/a> (last accessed 12\/04\/2023).<\/li>\n<\/ol>\n\n

    DERMATOLOGY PRACTICE 2023; 33(6): 20<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

    Terbinafine is considered the gold standard in the treatment of dermatophytosis, but pathogenic dermatophytes that are resistant to terbinafine pose a new threat. A Swiss research team involving the Department…<\/p>\n","protected":false},"author":7,"featured_media":371904,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"pmpro_default_level":"","cat_1_feature_home_top":false,"cat_2_editor_pick":false,"csco_eyebrow_text":"Journal Club ","footnotes":""},"category":[11340,11508,11406,11548],"tags":[73142,13280,12223,73139,73137,73140],"powerkit_post_featured":[],"class_list":["post-371900","post","type-post","status-publish","format-standard","has-post-thumbnail","category-dermatology-and-venereology","category-education","category-infectiology","category-rx-en","tag-chuv-en","tag-dermatophytes","tag-resistance","tag-skin-fungi","tag-terbinafine-en","tag-terbinafine-resistance","pmpro-has-access"],"acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-04-15 11:35:59","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"wpml_current_locale":"en_US","wpml_translations":{"fr_FR":{"locale":"fr_FR","id":371907,"slug":"nouvelles-connaissances-sur-les-dermatophytes-resistants-a-la-terbinafine","post_title":"Nouvelles connaissances sur les dermatophytes r\u00e9sistants \u00e0 la terbinafine","href":"https:\/\/medizinonline.com\/fr\/nouvelles-connaissances-sur-les-dermatophytes-resistants-a-la-terbinafine\/"},"it_IT":{"locale":"it_IT","id":371913,"slug":"nuove-scoperte-sui-dermatofiti-resistenti-alla-terbinafina","post_title":"Nuove scoperte sui dermatofiti resistenti alla terbinafina","href":"https:\/\/medizinonline.com\/it\/nuove-scoperte-sui-dermatofiti-resistenti-alla-terbinafina\/"},"pt_PT":{"locale":"pt_PT","id":371919,"slug":"novas-descobertas-sobre-dermatofitos-resistentes-a-terbinafina","post_title":"Novas descobertas sobre dermat\u00f3fitos resistentes \u00e0 terbinafina","href":"https:\/\/medizinonline.com\/pt-pt\/novas-descobertas-sobre-dermatofitos-resistentes-a-terbinafina\/"},"es_ES":{"locale":"es_ES","id":371925,"slug":"nuevos-hallazgos-sobre-los-dermatofitos-resistentes-a-la-terbinafina","post_title":"Nuevos hallazgos sobre los dermatofitos resistentes a la terbinafina","href":"https:\/\/medizinonline.com\/es\/nuevos-hallazgos-sobre-los-dermatofitos-resistentes-a-la-terbinafina\/"}},"_links":{"self":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/371900","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/comments?post=371900"}],"version-history":[{"count":1,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/371900\/revisions"}],"predecessor-version":[{"id":371905,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/371900\/revisions\/371905"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media\/371904"}],"wp:attachment":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media?parent=371900"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/category?post=371900"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/tags?post=371900"},{"taxonomy":"powerkit_post_featured","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/powerkit_post_featured?post=371900"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}