Skip to main content
SpringerLink
Log in

Mapping the Global Spread of T. indotineae: An Update on Antifungal Resistance, Mutations, and Strategies for Effective Management

  • Review
  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

Introduction

The global spread of Trichophyton indotineae presents a pressing challenge in dermatophytosis management. This systematic review explores the current landscape of T. indotineae infections, emphasizing resistance patterns, susceptibility testing, mutational analysis, and management strategies.

Methods

A literature search was conducted in November 2023 using Embase, PubMed, Scopus, and Web of Science databases. Inclusion criteria covered clinical trials, observational studies, case series, or case reports with T. indotineae diagnosis through molecular methods. Reports on resistance mechanisms, antifungal susceptibility testing, and management were used for data extraction.

Results and Discussion

A total of 1148 articles were identified through the systematic search process, with 45 meeting the inclusion criteria. The global spread of T. indotineae is evident, with cases reported in numerous new countries in 2023. Tentative epidemiological cut-off values (ECOFFs) suggested by several groups provide insights into the likelihood of clinical resistance. The presence of specific mutations, particularly Phe397Leu, correlate with higher minimum inhibitory concentrations (MICs), indicating potential clinical resistance. Azole resistance has also been reported and investigated in T. indotineae, and is a growing concern. Nevertheless, itraconazole continues to be an alternative therapy. Recommendations for management include oral or combination therapies and individualized approaches based on mutational analysis and susceptibility testing.

Conclusion

Trichophyton indotineae poses a complex clinical scenario, necessitating enhanced surveillance, improved diagnostics, and cautious antifungal use. The absence of established clinical breakpoints for dermatophytes underscores the need for further research in this challenging field.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

References

  1. Nenoff P, Uhrlaß S, Verma SB, Panda S. Trichophyton mentagrophytes ITS genotype VIII and Trichophyton indotineae: A terminological maze, or is it? Indian J Dermatol Venereol Leprol. 2022;88:586–9.

    Article  PubMed  Google Scholar 

  2. Uhrlaß S, Verma SB, Gräser Y, Rezaei-Matehkolaei A, Hatami M, Schaller M, et al. Trichophyton indotineae—an emerging pathogen causing recalcitrant dermatophytoses in India and worldwide—a multidimensional perspective. J Fungi (Basel). 2022;8:757.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sacheli R, Hayette MP. Antifungal resistance in dermatophytes: genetic considerations, clinical presentations and alternative therapies. J Fungi (Basel). 2021;7:983.

    Article  CAS  PubMed  Google Scholar 

  4. Jabet A, Normand AC, Brun S, Dannaoui E, Bachmeyer C, Piarroux R, et al. Trichophyton indotineae, from epidemiology to therapeutic. J Mycol Med. 2023;33:101383.

    Article  PubMed  Google Scholar 

  5. Gupta AK, Polla Ravi S, Wang T, Cooper EA, Lincoln SA, Foreman HC, et al. Antifungal resistance, susceptibility testing and treatment of recalcitrant dermatophytosis caused by Trichophyton indotineae: a North American perspective on management. Am J Clin Dermatol. 2023;24:927–38.

    Article  PubMed  Google Scholar 

  6. Chowdhary A, Singh A, Kaur A, Khurana A. The emergence and worldwide spread of the species Trichophyton indotineae causing difficult-to-treat dermatophytosis: a new challenge in the management of dermatophytosis. PLoS Pathog. 2022;18:e1010795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;2021:n71.

    Article  Google Scholar 

  8. OCEBM Levels of Evidence Working Group. The Oxford 2011 Levels of Evidence. 2011 [cited 2023 Dec 27]. Available from: https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-levels-of-evidence.

  9. Jia S, Long X, Hu W, Zhu J, Jiang Y, Ahmed S, et al. The epidemic of the multiresistant dermatophyte Trichophyton indotineae has reached China. Front Immunol. 2023;13:1113065.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Messina F, Santiso G, Romero M, Bonifaz A, Fernandez M, Marin E. First case report of tinea corporis caused by Trichophyton indotineae in Latin America. Med Mycol Case Rep. 2023;41:48–51.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kong X, Song G, Mei H, Zheng H, Tang C, de Hoog S, et al. The domestic isolation of terbinafine- and itraconazole-resistant Trichophyton indotineae in Chinese Mainland. Mycopathologia. 2023;188:383–93.

    Article  CAS  PubMed  Google Scholar 

  12. Bortoluzzi P, Prigitano A, Sechi A, Boneschi V, Germiniasi F, Esposto MC, et al. Report of terbinafine resistant Trichophyton spp. in Italy: Clinical presentations, molecular identification, antifungal susceptibility testing and mutations in the squalene epoxidase gene. Mycoses. 2023;66:680–7.

    Article  CAS  PubMed  Google Scholar 

  13. Dashti Y, Alobaid K, Al-Rashidi S, Dashti M, AbdulMoneim MH, Al-Enezi M, et al. Autochthonous case of Trichophyton indotineae in Kuwait. J Med Mycol. 2023;33:101432.

    Article  Google Scholar 

  14. Villa-Gonzalez JM, Pascual Ares M, López-Soria LM, Gonzalez-Hermosa MR, Gardeazabal García J, Lasa EO. Extensive tinea corporis caused by Trichophyton indotineae: report of a case in Spain. J Eur Acad Dermatol Venereol. 2023;38:e22–3.

    PubMed  Google Scholar 

  15. Durdu M, Kandemir H, Karakoyun AS, Ilkit M, Tang C, de Hoog S. First Terbinafine-resistant Trichophyton indotineae isolates with Phe397Leu and/or Thr414His mutations in Turkey. Mycopathologia. 2023;188:2.

    Article  CAS  PubMed  Google Scholar 

  16. Cañete-Gibas CF, Mele J, Patterson HP, Sanders CJ, Ferrer D, Garcia V, et al. Terbinafine-resistant dermatophytes and the presence of Trichophyton indotineae in North America. J Clin Microbiol. 2023;61:e0056223.

    Article  PubMed  Google Scholar 

  17. Caplan AS, Chaturvedi S, Zhu Y, Todd GC, Yin L, Lopez A, et al. Notes from the field: first reported U.S. cases of Tinea caused by Trichophyton indotineae—New York City, December 2021–March 2023. Morb Mortal Wkly Rep. 2023;72:536.

    Article  Google Scholar 

  18. Gupta AK, Venkataraman M, Hall DC, Cooper EA, Summerbell RC. The emergence of Trichophyton indotineae: implications for clinical practice. Int J Dermatol. 2023;62:857–61.

    Article  PubMed  Google Scholar 

  19. Caplan AS, Zakhem GA, Pomeranz MK. Trichophyton mentagrophytes internal transcribed spacer genotype VIII. JAMA Dermatol. 2023;159:1130.

    Article  PubMed  Google Scholar 

  20. Verma SB, Panda S, Nenoff P, Singal A, Rudramuruthy SM, Uhrlass S, et al. The unprecedented epidemic-like scenario of dermatophytosis in India: I. Epidemiology, risk factors and clinical features. Indian J Dermatol Venereol Leprol. 2021;87:154–75.

    Article  PubMed  Google Scholar 

  21. Mukherjee PK, Leidich SD, Isham N, Leitner I, Ryder NS, Ghannoum MA. Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine. Antimicrob Agents Chemother. 2003;47:82–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Iyer KR, Revie NM, Fu C, Robbins N, Cowen LE. Treatment strategies for cryptococcal infection: challenges, advances and future outlook. Nat Rev Microbiol. 2021;19(7):454–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Fattahi A, Shirvani F, Ayatollahi A, Rezaei-Matehkolaei A, Badali H, Lotfali E, 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;60:686–92.

    Article  CAS  PubMed  Google Scholar 

  24. Gueneau R, Joannard B, Haddad N, Alby F, Jullien V, Schlatter J, et al. Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae, successfully treated with topical voriconazole. Int J Antimicrob Agents. 2022;60:106677.

    Article  CAS  PubMed  Google Scholar 

  25. 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. 2020;6:1–20.

    Article  Google Scholar 

  26. Dellière S, Joannard B, Benderdouche M, Mingui A, Gits-Muselli M, Hamane S, et al. Emergence of difficult-to-treat tinea corporis caused by Trichophyton mentagrophytes complex isolates, Paris, France. Emerg Infect Dis. 2022;28:224–8.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Dogra S, Shaw D, Rudramurthy SM. Antifungal drug susceptibility testing of dermatophytes: laboratory findings to clinical implications. Indian Dermatol Online J. 2019;10:225.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Astvad KMT, Hare RK, Jørgensen KM, Saunte DML, Thomsen PK, Arendrup MC. Increasing terbinafine resistance in Danish Trichophyton isolates 2019–2020. J Fungi. 2022;8:150.

    Article  CAS  Google Scholar 

  29. 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.

    Article  CAS  PubMed  Google Scholar 

  30. Russo G, Toutous Trellu L, Fontao L, Ninet B. Towards an early clinical and biological resistance detection in dermatophytosis: about 2 cases of Trichophyton indotineae. J Fungi. 2023;9:733.

    Article  Google Scholar 

  31. Shen JJ, Arendrup MC, Verma S, Saunte DML. The emerging terbinafine-resistant trichophyton epidemic: What is the role of antifungal susceptibility testing? Dermatology. 2022;238:60–79.

    Article  CAS  PubMed  Google Scholar 

  32. Arendrup MC, Jørgensen KM, Guinea J, Lagrou K, Chryssanthou E, Hayette MP, et al. Comment on: Multicentre validation of a EUCAST method for the antifungal susceptibility testing of microconidia-forming dermatophytes. J Antimicrob Chemother. 2022;77:1212–3.

    Article  PubMed  Google Scholar 

  33. Blanchard G, Amarov B, Fratti M, Salamin K, Bontems O, Chang YT, et al. Reliable and rapid identification of terbinafine resistance in dermatophytic nail and skin infections. J Eur Acad Dermatol Venereol. 2023;37:2080–9.

    Article  CAS  PubMed  Google Scholar 

  34. 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.

    Article  CAS  PubMed  Google Scholar 

  35. Kong X, Tang C, Singh A, Ahmed SA, Al-Hatmi AMS, Chowdhary A, et al. Antifungal susceptibility and mutations in the squalene epoxidase gene in dermatophytes of the Trichophyton mentagrophytes species complex. Antimicrob Agents Chemother. 2021;65:e0005621.

    Article  PubMed  Google Scholar 

  36. Martinez-Rossi NM, Peres NTA, Bitencourt TA, Martins MP, Rossi A. State-of-the-art dermatophyte infections: epidemiology aspects, pathophysiology, and resistance mechanisms. J Fungi (Basel). 2021;7:629.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Brasch J, Gräser Y, Beck-Jendroscheck V, Voss K, Torz K, Walther G, et al. “Indian” strains of Trichophyton mentagrophytes with reduced itraconazole susceptibility in Germany. JDDG J German Soc Dermatol. 2021;19:1723–7.

    Google Scholar 

  38. Gupta AK, Talukder M, Carviel JL, Cooper EA, Piguet V. Combatting antifungal resistance: paradigm shift in the diagnosis and management of onychomycosis and dermatomycosis. J Eur Acad Dermatol Venereol. 2023;37:1706–17.

    Article  CAS  PubMed  Google Scholar 

  39. Yamada T, Yaguchi T, Tamura T, Pich C, Salamin K, Feuermann M, et al. Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2. Mycoses. 2021;64:936–46.

    Article  CAS  PubMed  Google Scholar 

  40. Monod M, Feuermann M, Salamin K, Fratti M, Makino M, Alshahni MM, et al. Trichophyton rubrum azole resistance mediated by a new ABC transporter, TruMDR3. Antimicrob Agents Chemother. 2019;63:e00863-e919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Yamada T, Yaguchi T, Maeda M, Alshahni MM, Salamin K, Guenova E, et al. Gene amplification of CYP51B: a new mechanism of resistance to azole compounds in Trichophyton indotineae. Antimicrob Agents Chemother. 2022;66:e0005922.

    Article  PubMed  Google Scholar 

  42. Burmester A, Hipler UC, Elsner P, Wiegand C. Point mutations in the squalene epoxidase erg1 and sterol 14-α demethylase erg11 gene of T. indotineae isolates indicate that the resistant mutant strains evolved independently. Mycoses. 2022;65:97–102.

    Article  CAS  PubMed  Google Scholar 

  43. Shafiei M, Peyton L, Hashemzadeh M, Foroumadi A. History of the development of antifungal azoles: a review on structures, SAR, and mechanism of action. Bioorg Chem. 2020;104:104240.

    Article  CAS  PubMed  Google Scholar 

  44. Yamada T, Nojo H, Kano R. Long amplification PCR (LA-PCR) detection of azole resistant Trichophyton indotineae. Mycopathologia. 2023;188:1085–8.

    Article  CAS  PubMed  Google Scholar 

  45. Yamada T, Maeda M, Nagai H, Salamin K, Chang Y-T, Guenova E, et al. Two different types of tandem sequences mediate the overexpression of TinCYP51B in azole-resistant Trichophyton indotineae. Antimicrob Agents Chemother. 2023;67:e0093323.

    Article  PubMed  Google Scholar 

  46. Crotti S, Cruciani D, Spina S, Piscioneri V, Natalini Y, Pezzotti G, et al. A terbinafine sensitive Trichophyton indotineae strain in Italy: the first clinical case of tinea corporis and onychomycosis. J Fungi. 2023;9:865.

    Article  Google Scholar 

  47. Sardana K, Khurana A, Panesar S, Singh A. Super bioavailable itraconazole and its place and relevance in recalcitrant dermatophytosis: revisiting skin levels of itraconazole and minimum inhibitory concentration data. Indian Dermatol Online J. 2021;12:1–1.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Thakur R, Kushwaha P, Kalsi AS. Tinea universalis due to Trichophyton indotineae in an adult male. Indian J Med Microbiol. 2023;46:100476.

    Article  PubMed  Google Scholar 

  49. Song G, Kong X, Li X, Liu W, Liang G. Prior selection of itraconazole in the treatment of recalcitrant Trichophyton indotineae infection: real-world results from retrospective analysis. Mycoses. 2023;67:e13663.

    Article  PubMed  Google Scholar 

  50. Khurana A, Agarwal A, Agrawal D, Panesar S, Ghadlinge M, Sardana K, et al. Effect of different itraconazole dosing regimens on cure rates, treatment duration, safety, and relapse rates in adult patients with tinea corporis/cruris: a randomized clinical trial. JAMA Dermatol. 2022;158:1269–78.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Jabet A, Brun S, Normand AC, Imbert S, Akhoundi M, Dannaoui E, et al. Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae. France Emerg Infect Dis. 2022;28:229–33.

    Article  CAS  PubMed  Google Scholar 

  52. Harada K, Maeda T, Kano R. Extensive tinea corporis caused by a virulent strain of Trichophyton interdigitale. J Dermatol. 2021;48:e190–1.

    Article  PubMed  Google Scholar 

  53. Kolarczyková D, Lysková P, Švarcová M, Kuklová I, Dobiáš R, Mallátová N, et al. Terbinafine resistance in Trichophyton mentagrophytes and Trichophyton rubrum in the Czech Republic: a prospective multicentric study. Mycoses. 2024;67:e13708.

    Article  PubMed  Google Scholar 

  54. Singh S, Subba N, Tilak R. Efficacy of terbinafine and itraconazole in different doses and in combination in the treatment of tinea infection: a randomized controlled parallel group open labeled trial with clinico-mycological correlation. Indian J Dermatol. 2020;65:284.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Ravindra Babu P, Pravin AJS, Deshmukh G, Dhoot D, Samant A, Kotak B. Efficacy and safety of terbinafine 500 mg once daily in patients with dermatophytosis. Indian J Dermatol. 2017;62:395.

    Article  PubMed  Google Scholar 

  56. Xie W, Kong X, Zheng H, Mei H, Ge N, Hu S, et al. Rapid Emergence of Recalcitrant Dermatophytosis by a Cluster of Multidrug-Resistant Trichophyton indotineae, China. Br J Dermatol [Internet]. 2024 [cited 2024 Jan 8]; Available from: https://pubmed-ncbi-nlm-nih-gov.myaccess.library.utoronto.ca/38180270/.

Download references

Funding

No funding was received to assist with the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Division of Dermatology, Department of Medicine, University of Toronto School of Medicine, Toronto, ON, Canada

    Aditya K. Gupta

  2. Mediprobe Research Inc., 645 Windermere Road, London, ON, N5X 2P1, Canada

    Aditya K. Gupta, Shruthi Polla Ravi & Tong Wang

  3. Bako Diagnostics, Alpharetta, GA, USA

    Wayne L. Bakotic

  4. Department of Dermatology, Tel Hashomer, Tel Aviv University, Tel Aviv, Israel

    Avner Shemer

Authors
  1. Aditya K. Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shruthi Polla Ravi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wayne L. Bakotic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Avner Shemer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aditya K. Gupta.

Ethics declarations

Conflict of interest

AKG, SPR, TW, and AS have no conflict of interest to declare. WLB is an employee of Bako Diagnostics (Alpharetta, GA, USA).

Additional information

Handling Editor: Vishnu Chaturvedi.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 549 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gupta, A.K., Polla Ravi, S., Wang, T. et al. Mapping the Global Spread of T. indotineae: An Update on Antifungal Resistance, Mutations, and Strategies for Effective Management. Mycopathologia 189, 45 (2024). https://doi.org/10.1007/s11046-024-00856-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11046-024-00856-z

Keywords

Search

Navigation