Fungal skin infections are the most common skin disease worldwide. Superficial mycoses caused by Trichophyton rubrum and T.interdigitale are one of the leading causes for patients to seek dermatological care. Terbinafine (TRB), acting through squalene epoxidase (SQLE) inhibition, is the drug of choice for curing both species. However, TRB-resistant cases are increasing. Between 2013 and 2021, we examined TRB-sensitivity in 5435 consecutive strains of T. rubrum and T. interdigitale by testing their growth capacity on Sabouraud’s medium containing TRB. One percent of the cohort (n= 47) showed reduced TRB sensitivity by being able to grow on this medium. In all of these strains, we identified mutations within the SQLE. SQLE in 46 strains had a point mutation leading to an amino acid substitution at one of five positions (L393, F397, Q408, F415, H440) of the SQLE. SQLE in one strain had a nine bp deletion. Overall, point mutation F397L was the most common, representing 34% of the resistant strains (n=16). We used the broth microdilution method, gold standard to test susceptibility of microorganisms, to acquire MICs (minimum inhibitory concentration) for all resistant strains. Each mutation was associated with a specific range of MICs, varying between 0.015 and 8.0 µg/ml. The highest MICs were measured in strains with the L393F mutation, followed by F397L. MIC of 0.015 µg/ml already conferred clinical resistance to TRB, defining a minimum MIC breakpoint for predicting TRB failure. Any strain growing on Sabouraud’s medium containing TRB potentially confers clinical resistance. In multiple cases, based on our data, the treatment was adapted and a complete cure achieved using systemic itraconazole or fluconazole. TRB-resistance is becoming a global health threat. Here, we determine its prevalence in the largest cohort up to today, describing in detail the underlying molecular mechanisms. We validate a novel method, which can rapidly and reliably identify TRB-resistant strains and present our clinical experience with treatment of TRB-resistant infections.

Fungal skin infections are the most common skin disease worldwide. Superficial mycoses caused by Trichophyton rubrum and T.interdigitale are one of the leading causes for patients to seek dermatological care. Terbinafine (TRB), acting through squalene epoxidase (SQLE) inhibition, is the drug of choice for dermatophytosis treatment. However, TRB-resistant cases are increasing. Between 2013 and 2021, we examined TRB-sensitivity in 5435 consecutive strains of _T. rubrum_ and _T. interdigitale_ by testing their growth capacity on Sabouraud’s medium containing 0.2 µg/ml of TRB. One percent of the cohort (n= 47) showed reduced TRB sensitivity by being able to grow on this medium. In all of these strains, we identified mutations within the SQLE. SQLE in 46 strains had a point mutation leading to an amino acid substitution at one of five positions (L393, F397, Q408, F415, H440) of the SQLE. SQLE in one strain had a nine bp deletion. Overall, point mutation F397L was the most common, representing 34% of the resistant strains (n=16). We used the broth microdilution method, gold standard to test susceptibility of microorganisms, to acquire MICs (minimum inhibitory concentration) for all resistant strains. Each mutation was associated with a specific range of MICs, varying between 0.015 and 8.0 µg/ml. The highest MICs were measured in strains with the L393F mutation, followed by F397L. MIC of 0.015 µg/ml already conferred clinical resistance to TRB, defining a minimum MIC breakpoint for predicting TRB failure. Any strain growing on Sabouraud’s medium containing 0.2 µg/ml of TRB potentially confers clinical resistance. In multiple cases, based on our data, the treatment was adapted and a complete cure achieved using systemic itraconazole or fluconazole. TRB-resistance is becoming a global health threat. Here, we determine its prevalence in the largest cohort up to today, describing in detail the underlying molecular mechanisms. We validate a novel method, which can rapidly and reliably identify TRB-resistant strains and present our clinical experience with treatment of TRB-resistant infections.

ESDR086 - Terbinafine-resistant dermatophytosis: an emerging global health threat

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.