Terbinafine Resistance in <i>Trichophyton rubrum</i> and <i>Trichophyton indotineae</i>: A Literature Review

Background/Objectives: Terbinafine has been the gold standard for the management of superficial fungal infections. The etiological agent generally is <i>Trichophyton rubrum</i> (<i>T. rubrum</i>); however, there has been increased reporting of a new terbinafine-resistant stra...

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Main Authors: Aditya K. Gupta, Susmita, Hien C. Nguyen, Amanda Liddy, Vasiliki Economopoulos, Tong Wang
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/5/472
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author Aditya K. Gupta
Susmita
Hien C. Nguyen
Amanda Liddy
Vasiliki Economopoulos
Tong Wang
author_facet Aditya K. Gupta
Susmita
Hien C. Nguyen
Amanda Liddy
Vasiliki Economopoulos
Tong Wang
author_sort Aditya K. Gupta
collection DOAJ
description Background/Objectives: Terbinafine has been the gold standard for the management of superficial fungal infections. The etiological agent generally is <i>Trichophyton rubrum</i> (<i>T. rubrum</i>); however, there has been increased reporting of a new terbinafine-resistant strain of the <i>T. mentagrophytes complex</i> (<i>T. mentagrophytes</i> ITS genotype VIII otherwise known as <i>T. indotineae</i>). Here, we review the epidemiology, clinical features, diagnosis, and treatment of <i>T. rubrum</i> and <i>T. indotineae</i> infections. Methods: We conducted a systematic literature search using PubMed, Embase (Ovid), and Web of Science, resulting in 83 qualified studies with data summarized for clinical features, antifungal susceptibility, and terbinafine resistance mechanisms and mutations. Results: Dermatophytosis is most commonly caused by <i>T. rubrum</i>; however, in certain parts of the world, especially in the Indian subcontinent, <i>T. indotineae</i> infections have been reported more frequently. The majority of <i>T. rubrum</i> isolates remain susceptible to terbinafine (over 60% of isolates show MIC<sub>50</sub> and MIC<sub>90</sub> < 0.5 µg/mL). In contrast, for <i>T. indotineae</i>, 30% of isolates exhibit MIC<sub>50</sub> ≥ 0.5 µg/mL and 80% exhibit MIC<sub>90</sub> ≥ 0.5 µg/mL. Frequently detected squalene epoxidase (<i>SQLE</i>) mutations in <i>T. rubrum</i> are Phe397Leu/Ile (41.6%) and Leu393Phe (20.8%); in <i>T. indotineae</i>, these include Phe397Leu (33.0%) and Ala448Thr (24.5%). Other potential terbinafine resistance mechanisms in <i>T. rubrum</i> and <i>T. indotineae</i> are discussed. Conclusions: <i>T. rubrum</i> generally remain susceptible in vitro to terbinafine in contrast to <i>T. indotineae</i>. The essential components of an effective antifungal stewardship emphasize accurate clinical and laboratory diagnosis, susceptibility testing, and appropriate antifungal therapy selection with a multidisciplinary approach.
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spelling doaj-art-158665a424d14547b0124b313b4e81fa2025-08-20T02:33:43ZengMDPI AGAntibiotics2079-63822025-05-0114547210.3390/antibiotics14050472Terbinafine Resistance in <i>Trichophyton rubrum</i> and <i>Trichophyton indotineae</i>: A Literature ReviewAditya K. Gupta0Susmita1Hien C. Nguyen2Amanda Liddy3Vasiliki Economopoulos4Tong Wang5Division of Dermatology, Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3H2, CanadaMediprobe Research Inc., London, ON N5X 2P1, CanadaMediprobe Research Inc., London, ON N5X 2P1, CanadaMediprobe Research Inc., London, ON N5X 2P1, CanadaMediprobe Research Inc., London, ON N5X 2P1, CanadaMediprobe Research Inc., London, ON N5X 2P1, CanadaBackground/Objectives: Terbinafine has been the gold standard for the management of superficial fungal infections. The etiological agent generally is <i>Trichophyton rubrum</i> (<i>T. rubrum</i>); however, there has been increased reporting of a new terbinafine-resistant strain of the <i>T. mentagrophytes complex</i> (<i>T. mentagrophytes</i> ITS genotype VIII otherwise known as <i>T. indotineae</i>). Here, we review the epidemiology, clinical features, diagnosis, and treatment of <i>T. rubrum</i> and <i>T. indotineae</i> infections. Methods: We conducted a systematic literature search using PubMed, Embase (Ovid), and Web of Science, resulting in 83 qualified studies with data summarized for clinical features, antifungal susceptibility, and terbinafine resistance mechanisms and mutations. Results: Dermatophytosis is most commonly caused by <i>T. rubrum</i>; however, in certain parts of the world, especially in the Indian subcontinent, <i>T. indotineae</i> infections have been reported more frequently. The majority of <i>T. rubrum</i> isolates remain susceptible to terbinafine (over 60% of isolates show MIC<sub>50</sub> and MIC<sub>90</sub> < 0.5 µg/mL). In contrast, for <i>T. indotineae</i>, 30% of isolates exhibit MIC<sub>50</sub> ≥ 0.5 µg/mL and 80% exhibit MIC<sub>90</sub> ≥ 0.5 µg/mL. Frequently detected squalene epoxidase (<i>SQLE</i>) mutations in <i>T. rubrum</i> are Phe397Leu/Ile (41.6%) and Leu393Phe (20.8%); in <i>T. indotineae</i>, these include Phe397Leu (33.0%) and Ala448Thr (24.5%). Other potential terbinafine resistance mechanisms in <i>T. rubrum</i> and <i>T. indotineae</i> are discussed. Conclusions: <i>T. rubrum</i> generally remain susceptible in vitro to terbinafine in contrast to <i>T. indotineae</i>. The essential components of an effective antifungal stewardship emphasize accurate clinical and laboratory diagnosis, susceptibility testing, and appropriate antifungal therapy selection with a multidisciplinary approach.https://www.mdpi.com/2079-6382/14/5/472terbinafinesqualene epoxidase<i>Trichophyton rubrum</i><i>Trichophyton indotineae</i>antifungal drug resistance
spellingShingle Aditya K. Gupta
Susmita
Hien C. Nguyen
Amanda Liddy
Vasiliki Economopoulos
Tong Wang
Terbinafine Resistance in <i>Trichophyton rubrum</i> and <i>Trichophyton indotineae</i>: A Literature Review
Antibiotics
terbinafine
squalene epoxidase
<i>Trichophyton rubrum</i>
<i>Trichophyton indotineae</i>
antifungal drug resistance
title Terbinafine Resistance in <i>Trichophyton rubrum</i> and <i>Trichophyton indotineae</i>: A Literature Review
title_full Terbinafine Resistance in <i>Trichophyton rubrum</i> and <i>Trichophyton indotineae</i>: A Literature Review
title_fullStr Terbinafine Resistance in <i>Trichophyton rubrum</i> and <i>Trichophyton indotineae</i>: A Literature Review
title_full_unstemmed Terbinafine Resistance in <i>Trichophyton rubrum</i> and <i>Trichophyton indotineae</i>: A Literature Review
title_short Terbinafine Resistance in <i>Trichophyton rubrum</i> and <i>Trichophyton indotineae</i>: A Literature Review
title_sort terbinafine resistance in i trichophyton rubrum i and i trichophyton indotineae i a literature review
topic terbinafine
squalene epoxidase
<i>Trichophyton rubrum</i>
<i>Trichophyton indotineae</i>
antifungal drug resistance
url https://www.mdpi.com/2079-6382/14/5/472
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