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Volume 28, Number 1—January 2022
Dispatch

Extensive Dermatophytosis Caused by Terbinafine-Resistant Trichophyton indotineae, France

Arnaud Jabet1, Sophie Brun1, Anne-Cecile Normand, Sebastien Imbert, Mohammad Akhoundi, Eric Dannaoui, Laeticia Audiffred, Francois Chasset, Arezki Izri, Liliane Laroche, Renaud Piarroux, Claude Bachmeyer, Christophe Hennequin, and Alicia Moreno Sabater
Author affiliations: Assistance Publique-Hôpitaux de Paris, Paris, France (A. Jabet, S. Brun, A.-C. Normand, M. Akhoundi, E. Dannaoui, L. Audiffred, F. Chasset, A. Izri, L. Laroche, R. Piarroux, C. Bachmeyer, C. Hennequin, A. Moreno Sabater); Université Sorbonne Paris Nord, Bobigny, France (S. Brun); Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France (S. Imbert); Université de Bordeaux, Pessac, France (S. Imbert); Université de Paris, Paris (E. Dannaoui); Sorbonne Université, Paris (F. Chasset, R. Piarroux, C. Hennequin, A. Moreno Sabater); Aix-Marseille Université Unité des virus émergents, Marseille, France (A. Izri).

Main Article

Table

Characteristics of extensive dermatophytosis case-patients diagnosed with Trichophyton indotineae in France*

Patient no. Year Patient country of origin Treatments† Clinical outcome‡ Follow up ITS genotype§ TRB MIC,¶
μg/mL		 SQLE#
substitution		 ITR MIC,
μg/mL		 VOR MIC,
μg/mL		 AMO MIC,
μg/mL
1
 2017
 India
 Oral and cream TRB 1 mo
 Clinical cure; negative MyE
 No relapse after 6 mo
 ND
 ND
 ND
 ND
 ND
 ND
2
 2018
 Bangladesh
 TRB 1 mo
 Improvement§ after 1 mo
 Lost to follow-up
 ND
 ND
 ND
 ND
 ND
 ND
3
 2019
 Bangladesh
 TRB 2 mo
 Clinical cure
 No relapse 1 y later
 T. indotineae
 0.06
 None
 0.125
 0.125
 0.125
4
 2019
 Bangladesh
 TRB 3 mo, GRS 3 mo, ECZ 3 mo
 No improvement after 9 mo; positive MyE
 Lost to follow-up
 T. indotineae
 2
 Leu393Ser
 ND
 ND
 ND
5
 2020
 Bangladesh
 TRB 2 mo
 No improvement after 2 mo; positive MyE
 Lost to follow-up
 T. indotineae
 >8
 Phe397Leu
 0.06
 0.06
 0.06
6
 2020
 Myanmar
 CCL 1 mo
 Clinical cure
 No relapse 1 y later
 T. indotineae
 0.06
 Ala448Thr
 0.125
 0.125
 0.06
7
 2020
 Bangladesh
 TRB 3 wk, BFN 3 wk
 Improvement after 6 wk
 Relapse 2 mo later
 T. indotineae
 2
 Leu393Ser
 0.016
 0.03
 0.06
8
 2020
 Bangladesh
 OMC 1 mo, MCN 1 mo
 Improvement after 2 mo
 Lost to follow-up
 ND
 ND
 ND
 ND
 ND
 ND
9
 2021
 Bangladesh
 TRB 2 mo
 Improvement after 1 mo; negative MyE
 Lost to follow-up
 T. indotineae
 0.06
 None
 0.06
 0.06
 0.125
10 2021 Bangladesh TRB 6 mo, GRS 6 mo No improvement after 1 y; positive MyE ITR 2 mo improvement T. indotineae 2 Phe397Leu Ala448Thr 0.25 0.5 0.01

*AMO, amorolfine; BFN, bifonazole; CCL, ciclopiroxolamine; ECZ, econazole; GRS, griseofulvin; ITR, itraconazole; ITS, internal transcribed spacer; MCN, miconazole; MyE, mycologic exam; ; ND, not determined; OMC, omoconazole; SQLE, squalene epoxidase enzyme; TRB, terbinafine; VOR, voriconazole. †Treatments: oral TRB (250 mg/d); oral GRS (1 g/d); 1% ECZ cream; 1% CCL cream; 1% BFN cream; 1% OMC cream; 2% MCN cream; oral ITR (400 mg/d). ‡Clinical cure was recorded when skin lesions disappeared after treatment; clinical improvement was recorded when patient reported a reduction of clinical symptoms (itching and inflammatory lesions). §T. indotineae ITS sequencing was performed using primers (Appendix Table). Registered under GenBank accession nos. MW959755–60. ¶TBR resistance was defined by a MIC50 >0.25 µg/mL (8). #For SQLE sequencing, the amplified fragment was cut in 2 using a total of 4 primers because it was >1,000 nt long, (Appendix Table). Registered under GenBank accession no. MZ318454–9.

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References
  1. Dogra  S, Uprety  S. The menace of chronic and recurrent dermatophytosis in India: Is the problem deeper than we perceive? Indian Dermatol Online J. 2016;7:73–6. DOIPubMedGoogle Scholar
  2. Bishnoi  A, Vinay  K, Dogra  S. Emergence of recalcitrant dermatophytosis in India. [Comment in Lancet Infect Dis. 2018;18:718–9.]. Lancet Infect Dis. 2018;18:250–1. DOIPubMedGoogle Scholar
  3. Nenoff  P, Verma  SB, Uhrlaß  S, Burmester  A, Gräser  Y. 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;62:6–10. DOIPubMedGoogle Scholar
  4. Chowdhary  A, Singh  A, Singh  PK, Khurana  A, Meis  JF. Perspectives on misidentification of Trichophyton interdigitale/Trichophyton mentagrophytes using internal transcribed spacer region sequencing: Urgent need to update the sequence database. Mycoses. 2019;62:11–5. DOIPubMedGoogle Scholar
  5. Singh  A, Masih  A, Monroy-Nieto  J, Singh  PK, Bowers  J, Travis  J, 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;133:103266. DOIPubMedGoogle Scholar
  6. Kano  R, Kimura  U, Kakurai  M, Hiruma  J, Kamata  H, Suga  Y, et al. Trichophyton indotineae sp. nov.: a new highly terbinafine-resistant anthropophilic dermatophyte species. Mycopathologia. 2020;185:947–58. DOIPubMedGoogle Scholar
  7. Tang  C, Kong  X, Ahmed  SA, Thakur  R, Chowdhary  A, Nenoff  P, et al. Taxonomy of the Trichophyton mentagrophytes/T. interdigitale species complex harboring the highly virulent, multiresistant genotype T. indotineae. Mycopathologia. 2021;186:315–26. DOIPubMedGoogle Scholar
  8. Ebert  A, Monod  M, Salamin  K, Burmester  A, Uhrlaß  S, Wiegand  C, et al. Alarming India-wide phenomenon of antifungal resistance in dermatophytes: A multicentre study. Mycoses. 2020;63:717–28. DOIPubMedGoogle Scholar
  9. Nenoff  P, Verma  SB, Ebert  A, Süß  A, Fischer  E, Auerswald  E, et al. Spread of terbinafine-resistant Trichophyton mentagrophytes type VIII (India) in Germany—“the tip of the iceberg? J Fungi (Basel). 2020;6:207. DOIPubMedGoogle Scholar
  10. Klinger  M, Theiler  M, Bosshard  PP. Epidemiological and clinical aspects of Trichophyton mentagrophytes/Trichophyton interdigitale infections in the Zurich area: a retrospective study using genotyping. J Eur Acad Dermatol Venereol. 2021;35:1017–25. DOIPubMedGoogle Scholar
  11. Saunte  DML, Pereiro-Ferreirós  M, Rodríguez-Cerdeira  C, Sergeev  AY, Arabatzis  M, Prohić  A, et al. Emerging antifungal treatment failure of dermatophytosis in Europe: take care or it may become endemic. J Eur Acad Dermatol Venereol. 2021;35:1582–6. DOIPubMedGoogle Scholar
  12. Office Français de protection des réfugiés et apatrides. 2016 activity report [cited on 19 Apr 2021]. https://ofpra.gouv.fr/sites/default/files/atoms/files/rapport_dactivite_ofpra_2016_1.pdf
  13. Singh  S, Chandra  U, Anchan  VN, Verma  P, Tilak  R. Limited effectiveness of four oral antifungal drugs (fluconazole, griseofulvin, itraconazole and terbinafine) in the current epidemic of altered dermatophytosis in India: results of a randomized pragmatic trial. Br J Dermatol. 2020;183:840–6. DOIPubMedGoogle Scholar
  14. Khurana  A, Masih  A, Chowdhary  A, Sardana  K, Borker  S, Gupta  A, et al. Correlation of in vitro susceptibility based on MICs and squalene epoxidase mutations with clinical response to terbinafine in patients with tinea corporis/cruris. Antimicrob Agents Chemother. 2018;62:e01038–18. DOIPubMedGoogle Scholar
  15. Arendrup  MC, Jørgensen  KM, Guinea  J, Lagrou  K, Chryssanthou  E, Hayette  MP, et al. Multicentre validation of a EUCAST method for the antifungal susceptibility testing of microconidia-forming dermatophytes. J Antimicrob Chemother. 2020;75:1807–19. DOIPubMedGoogle Scholar

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1These first authors contributed equally to this article.

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