Terbinafine Resistant Trichophyton Indotineae Isolated in Patients With Superficial Dermatophyte Infection in Canadian Patients

Abstract

Background

Trichophyton mentagrophytes type VIII (segregated as Trichophyton indotineae) is a new strain of antifungal resistant Trichophyton spp. that has been found in different countries around the world. This new strain has been found to be resistant to terbinafine.

Objectives

We present the clinical characteristics, diagnosis and treatment approach of Canadian patients with mycology and molecular confirmation of superficial mycosis caused by T. indotineae.

Methods

Mycology testing from cultures and PCR were used to confirm T. indotineae. We collected clinical information from patients with a confirmed diagnosis.

Results

We report eight Canadian patients mainly presenting with extensive superficial mycosis due to T. indotineae. Three patients presented lesions on the face in addition to lesions on their body. Four patients were initially started on itraconazole or fluconazole, one patient was started on topical therapy, and three patients were referred to infectious disease.

Conclusions

This new strain represents a dermatology and public health concern. Treatment guidelines are lacking. We include a practical approach and treatment recommendations for clinicians who will be encountering these emerging cases in Canada while waiting for evidence-based treatment guidelines.

Keywords

terbinafine-resistant tinea corporis dermatophyte infection

Get full access to this article

View all access options for this article.

References

de Hoog

GS.

Dukik

Monod

et al. Toward a novel multilocus phylogenetic taxonomy for the dermatophytes. Mycopathologia. 2017;182(1-2):5-31.doi:10.1007/s11046-016-0073-9

27783317

Martinez-Rossi

NM.

Peres

NTA.

Rossi

. Pathogenesis of dermatophytosis: sensing the host tissue. Mycopathologia. 2017;182(1-2):215-227.doi:10.1007/s11046-016-0057-9

27590362

Singh

Masih

Khurana

et al. High terbinafine resistance in Trichophyton interdigitale isolates in Delhi, India harbouring mutations in the squalene epoxidase gene. Mycoses. 2018;61(7):477-484.doi:10.1111/myc.12772

29577447

Nenoff

Verma

SB.

Uhrlaß

Burmester

Gräser

. A clarion call for preventing taxonomical errors of dermatophytes using the example of the novel Trichophyton mentagrophytes genotype VIII uniformly isolated in the Indian epidemic of superficial dermatophytosis. Mycoses. 2019;62(1):6-10.doi:10.1111/myc.12848

30187579

Uhrlass

Pchelin

Rezaei-Matehkolaei

et al. Molecular epidemiology of Trichophyton mentagrophytes - a new approach. 2018;56(Supplement 2):55.doi:10.1093/mmy/myy036

Kano

Kimura

Kakurai

et al. Trichophyton indotineae sp. nov.: A new highly terbinafine-resistant anthropophilic dermatophyte species. Mycopathologia. 2020;185(6):947-958.doi:10.1007/s11046-020-00455-8

32449054

Ebert

Monod

Salamin

et al. Alarming India-wide phenomenon of antifungal resistance in dermatophytes: A multicentre study. Mycoses. 2020;63(7):717-728.doi:10.1111/myc.13091

32301159

Taghipour

Shamsizadeh

Pchelin

et al. Emergence of terbinafine resistant Trichophyton mentagrophytes in Iran, harboring mutations in the squalene epoxidase (SQLE) gene. Infect Drug Resist. 2020;13:845-850.doi:10.2147/IDR.S246025

32214830

White

TJ.

Bruns

TD.

Lee

SB.

Taylor

. Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. In: Innis

MA.

Gelfand

DH.

Sninsky

JJ.

White

TJ.

, eds. PCR protocols: A guide to methods and applications. Elsevier; 1990.

10.

Bogale

Orr

M-J.

O’Hara

MJ.

Untereiner

. Systematics of catenulifera (anamorphic hyaloscyphaceae) with an assessment of the phylogenetic position of Phialophora hyalina. Fungal Biol. 2010;114(5-6):396-409.doi:10.1016/j.funbio.2010.02.006

20943150

11.

Weitzman

Summerbell

. The dermatophytes. Clin Microbiol Rev. 1995;8(2):240-259.doi:10.1128/CMR.8.2.240

7621400

12.

McClellan

KJ.

Wiseman

LR.

Markham

. Terbinafine. An update of its use in superficial mycoses. Drugs. 1999;58(1):179-202.doi:10.2165/00003495-199958010-00018

10439936

13.

Bishnoi

Vinay

Dogra

. Emergence of recalcitrant dermatophytosis in India. Lancet Infect Dis. 2018;18(3):250-251.doi:10.1016/S1473-3099(18)30079-3

29485088

14.

Singh

Masih

Monroy-Nieto

et al. A unique multidrug-resistant clonal Trichophyton population distinct from Trichophyton mentagrophytes/Trichophyton interdigitale complex causing an ongoing alarming dermatophytosis outbreak in India: genomic insights and resistance profile. Fungal Genet Biol. 2019;133(June):103266.doi:10.1016/j.fgb.2019.103266

31491507

15.

Rudramurthy

SM.

Shankarnarayan

SA.

Dogra

et al. Mutation in the squalene epoxidase gene of Trichophyton interdigitale and Trichophyton rubrum associated with allylamine resistance. Antimicrob Agents Chemother. 2018;62(5):1-9.doi:10.1128/AAC.02522-17

29530857

16.

Rengasamy

Chellam

Ganapati

. Systemic therapy of dermatophytosis: practical and systematic approach. Clin Dermatol Rev. 2017;1(3):19.doi:10.4103/CDR.CDR_36_17

17.

Rajagopalan

Inamadar

Mittal

et al. Expert consensus on the management of dermatophytosis in India (ectoderm India). BMC Dermatol. 2018;18(1):6. doi:10.1186/s12895-018-0073-1

30041646

18.

Fattahi

Shirvani

Ayatollahi

et al. Multidrug‐resistant Trichophyton mentagrophytes genotype VIII in an Iranian family with generalized dermatophytosis: report of four cases and review of literature. Int J Dermatol. 2021;60(6):686-692.doi:10.1111/ijd.15226

33047849

19.

Nenoff

Verma

SB.

Ebert

et al. Spread of terbinafine-resistant trichophyton mentagrophytes type VIII (India) in Germany–“the tip of the iceberg?”. J Fungi. 2020;6(4):207-220.doi:10.3390/jof6040207

20.

Schøsler

Andersen

LK.

Arendrup

MC.

Sommerlund

. Recurrent terbinafine resistant Trichophyton rubrum infection in a child with congenital ichthyosis. Pediatr Dermatol. 2018;35(2):259-260.doi:10.1111/pde.13411

29341312

21.

Chen

Ghannoum

Elewski

. Treatment-resistant tinea corporis, a potential public health issue. Br J Dermatol. 2021;184(1):164-165.doi:10.1111/bjd.19420

33428216

22.

Bhatia

VK.

Sharma

. Determination of minimum inhibitory concentrations of itraconazole, terbinafine and ketoconazole against dermatophyte species by broth microdilution method. Indian J Med Microbiol. 2015;33(4):533-537.doi:10.4103/0255-0857.167341

26470960

23.

Łagowski

Gnat

Nowakiewicz

Osińska

Dyląg

. Intrinsic resistance to terbinafine among human and animal isolates of Trichophyton mentagrophytes related to amino acid substitution in the squalene epoxidase. Infection. 2020;48(6):889-897.doi:10.1007/s15010-020-01498-1

32770418