• Ivan Bristow

The growing problem of dermatophyte resistance

For many years fungal skin infection, particularly tinea pedis has been a very common pathology which when diagnosed, was considered fairly straightforward to treat with the drugs currently available. In the last few years, however, there has been a documented increase in the growing numbers of patients, particularly in India and South-East Asia presenting with persistent and recalcitrant fungal skin infection with a rise in resistance to the current drugs such as terbinafine and azoles. This article looks at some of the most recent publications in dermatology highlighting this issue.





There has been a steady flow of dermatology papers from Asia discussing the issue around fungal skin infection, particularly from India. There are a number of reasons for this worrying trend. Firstly, in India, potent steroid creams combined with antifungal agents and antimicrobial agents are freely available and have been sold in large quantities over the counter. These preparations actually being cheaper than pure antifungal agents mean they are the first choice [1]. Topical steroids suppress the normal immune response and act fast to improve a patient’s symptoms but do little to eradicate the infection even when combined with an antifungal due to the steroid’s high potency. Without education and regulation, patients may also be applying these potent steroids for months or even years [2] with an underlying fungal skin infection. Consequently, fungal skin infection rates are high, have an unusual clinical presentation (making diagnosis more difficult), and spread more easily to others in a country with a warm climate conducive to fungal growth.


There is a more worrisome side to this problem. Drug resistance is something we are acutely aware of when it comes to bacterial infections, but the idea of fungal resistance is less often considered but the potential for this problem has been previously raised [3, 4]. One of the earliest reports of drug resistance relates to a case of dermatophyte infection showing resistance to griseofulvin in 1961 [5] with cases of azole resistance in the 1980s [6] and terbinafine resistance being reported in 2003 [7]. The problem predominantly has been evident in India [8, 9], one study collected samples from 402 patients across 8 regions in India and discovered an alarming 71% of samples demonstrated terbinafine resistance [8]. However, small numbers of cases of drug-resistant fungal skin infections have been reported in Japan [10], Denmark [7] and Germany [11, 12].


A recent paper [13] undertook a questionnaire survey of European Dermatologists in 20 countries and concluded that 17/20 countries had identified a total of 96 cases of fungal skin infection which showed clinical or mycological resistance including the United Kingdom. These included commons strains such as T. rubrum and T mentagrophytes. The response to the threat of resistance, if it continues to increase, will be more widespread testing of fungal samples to identify and detect where resistance is likely to be a problem, what drug they are suspectable to so that alternative drugs can be used to treat infections as they arise.



References


1. Verma SB: Emergence of recalcitrant dermatophytosis in India. Lancet Infect Dis 2018, 18(7):718-719.

2. Verma S, Madhu R: The Great Indian Epidemic of Superficial Dermatophytosis: An Appraisal. Indian J Dermatol 2017, 62(3):227-236.

3. Hudson MMT: Antifungal resistance and over-the-counter availability in the UK: a current perspective. J Antimicrob Chemother 2001, 48(3):345-350.

4. Evans EG: Causative pathogens in onychomycosis and the possibility of treatment resistance: a review. J Am Acad Dermatol 1998, 38(5 Pt 3):S32-36.

5. Michaelides P, Rosenthal SA, Sulzberger MB, Witten VH: Trichophyton tonsurans infection resistant to griseofulvin. A case demonstrating clinical and in vitro resistance. Arch Dermatol 1961, 83:988-990.

6. Ryley JF, Wilson RG, Barrett-Bee KJ: Azole resistance in Candida albicans. Sabouraudia 1984, 22:53-63.

7. Pai V, Ganavalli A, Kikkeri NN: Antifungal Resistance in Dermatology. Indian J Dermatol 2018, 63(5):361-368.

8. Ebert A, Monod M, Salamin K, Burmester A, Uhrlaß S, Wiegand C, Hipler U-C, Krüger C, Koch D, Wittig F et al: Alarming India-wide phenomenon of antifungal resistance in dermatophytes: A multicentre study. Mycoses 2020, n/a(n/a).

9. Singh A, Masih A, Khurana A, Singh PK, Gupta M, Hagen F, Meis JF, Chowdhary A: High terbinafine resistance in Trichophyton interdigitale isolates in Delhi, India harbouring mutations in the squalene epoxidase gene. Mycoses 2018, 61(7):477-484.

10. Kimura U, Hiruma M, Kano R, Matsumoto T, Noguchi H, Takamori K, Suga Y: Caution and warning: Arrival of terbinafine-resistant Trichophyton interdigitale of the Indian genotype, isolated from extensive dermatophytosis, in Japan. The Journal of Dermatology 2020, 47(5):e192-e193.

11. Süß A, Uhrlaß S, Ludes A, Verma SB, Monod M, Krüger C, Nenoff P: [Extensive tinea corporis due to a terbinafine-resistant Trichophyton mentagrophytes isolate of the Indian genotype in a young infant from Bahrain in Germany]. Hautarzt 2019, 70(11):888-896.

12. Nenoff P, Verma SB, Ebert A, Süß A, Fischer E, Auerswald E, Dessoi S, Hofmann W, Schmidt S, Neubert K et al: Spread of Terbinafine-Resistant Trichophyton mentagrophytes Type VIII (India) in Germany-"The Tip of the Iceberg?". J Fungi (Basel) 2020, 6(4).

13. Saunte DML, Pereiro-Ferreirós M, Rodríguez-Cerdeira C, Sergeev AY, Arabatzis M, Prohić A, Piraccini BM, Lecerf P, Nenoff P, Kotrekhova LP et al: Emerging antifungal treatment failure of dermatophytosis in Europe: take care or it may become endemic. J Eur Acad Dermatol Venereol 2021, 35(7):1582-1586.

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