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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Summary: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.
ISSN:2079-6382