Rising terbinafine resistance in skin fungal infections sparks alarm

Australian clinicians urged to consider genetic testing as new review reveals key mutations driving terbinafine treatment failures.

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The common fungal skin infection dermatophytosis is becoming harder to treat as global cases of terbinafine resistance climb – and Australia is not immune. 

A systematic review published in the Australasian Journal of Dermatology highlights the growing challenge for clinicians and calls for a paradigm shift in how clinicians diagnose and manage resistant infections. 

Terbinafine, a first-line antifungal that works by inhibiting the squalene epoxidase (SQLE) enzyme, has long been the cornerstone of treatment for dermatophyte infections. 

However, resistance to terbinafine is growing globally, with cases reported in Australia and strong indications that resistant strains have roots in South Asia. 

“There is an alarming rise in not only the number of cases of trichophyton dermatophytosis, but also a rise in the number of recurrent and clinically resistant cases,” the authors wrote. 

“Large outbreaks were first described across the Indian subcontinent; however, there are now reported cases in patients without a travel history, which highlights local human-to-human transmission. 

“This reflects a concerning global epidemiological shift and a need for more robust surveillance. In Australia, terbinafine-resistant dermatophytosis has now been documented, with some reports that up to 18% of trichophyton dermatophytosis is resistant to terbinafine.” 

The researchers said several factors may be contributing to this rise, including “poor prescribing practices”.  

“In Australia, terbinafine is a first line therapy for all forms of dermatophytosis. Topical formulations are available over the counter, and oral terbinafine is both affordable and subsidised under the Pharmaceutical Benefits Scheme (PBS) for severe onychomycosis,” they wrote. 

“These factors may be inadvertently promoting overuse and under-supervised treatment, increasing the risk of resistance development. 

“This study highlights the paucity of studies reporting on clinical antifungal resistance confirmed by in vitro MIC data or SQLE mutation data. Furthermore, there is a lack of studies reporting on successful alternatives therapies for treatment failure with terbinafine that are supported by corresponding susceptibility data.” 

The researchers examined studies from 2000 to 2023 and found strong genetic links to terbinafine resistance in Trichophyton species, the primary culprits behind these infections. 

Of 149 patients with documented terbinafine use, 94 showed confirmed clinical resistance tied to SQLE gene mutations, including F397L, L393F and A448T. These mutations were associated with a markedly increased risk of resistance. 

The study also calculated a provisional minimum inhibitory concentration (MIC) threshold of 1.69μg/mL for terbinafine resistance, though no standardised global breakpoints currently exist. 

This lack of benchmarks complicated clinical interpretation and treatment decisions, the researchers said. 

“Routine SQLE mutation testing in cases of suspected terbinafine-resistant dermatophytosis could enhance diagnostic accuracy and inform more effective, timely treatment decisions,” they wrote.  

“Identifying specific mutations may guide clinicians in selecting alternative antifungal agents earlier in the treatment course, reducing morbidity and improving outcomes.” 

The researchers said the findings had important implications for antifungal stewardship and public health policy.  

“Routine susceptibility testing and molecular diagnostics could help prevent the inappropriate use of terbinafine, reduce treatment failures and slow the spread of resistance,” they concluded. 

“Surveillance systems that monitor regional resistance trends, coupled with clinician education on interpreting MIC and mutation data, will be vital in containing this emerging threat.” 

Australasian Journal of Dermatology, July 2025