Soon after the use of griseofulvin as a specific treatment for dermatophytosis (ringworm), dermatologists have noticed resistance to antifungal drugs in some patients. This may be due to underlying immunomodulating diseases in some cases, or compromised drug penetration in some locations of onychomycosis, A few patients, usually with tinea cruris or corporis are resistant to therapy or relapse rapidly thereafter. 

Evidence indicates the actuality of increased minimum inhibitory concentrations to griseofulvin, signifying drug resistance, in dermatophytes isolated from these cases. This problem, however, is being solved by oral azole antifungals, like ketoconazole. Nevertheless, it’s worth mentioning that therapeutic failure and in vitro resistance have been reported in the past when azoles were used to treat these infections. 

Azoles work differently from griseofulvin. They inhibit the α-demethylase enzyme in the fungal cell membrane, thus stopping the ergosterol biosynthesis. Until now, there weren′t any reports known describing resistance to terbinafine, which targets squalene epoxidase, however, Shen et al. have shown some evidence against it.

This situation is challenging as there is a recent and progressive increase in cases of widespread and treatment-unresponsive tinea corporis/cruris. A pioneer report from India, describes the patients being predominantly infected by a new strain of Trichophyton mentagrophytes, although few caused by T. rubrum. There also exist some informal reports of very similar recalcitrant infections in Bangladesh and from the Middle East and Sub-Saharan Africa. Europe has also reported similar cases with a common challenge being treatment failure with terbinafine. 

• Gradually, this sporadic nuisance is changing into a global public health crisis. The situation makes us think again-
• Is there any relation between the old cases and the new emerging strains in India with evidence of resistance to terbinafine or even azoles? 
• Where must be the origin of this new epidemic?
• How far has it spread globally? 
• How to handle this situation? 

Few cases of azole resistance dermatophytes have demonstrated overexpression of a trans-membrane drug transporter, TruMDR3. In vitro studies indicate that its effects can be opposed by the milbemycins which is a drug family often used in veterinary medicine as antiparasitics. 

However, some researchers have described a mutation in the squalene epoxidase gene itself in the new resistant strains – instead of a defect in trans-membrane drug transport. 

This global spread of resistant infections with different resistance mechanisms, and the occurrence of a new dermatophytes strain demands quick investigations.

Source-Hay RJ. The Spread of Resistant Tinea and the Ingredients of a Perfect Storm, Dermatology, 2021. DOI: 10.1159/000515291