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Resistance to Terbinafine in Trichophyton mentagrophytes and Trichophyton rubrum: Situation in the Czech Republic and in the World

Czech version

Authors: D. Kolarczyková 1;  P. Lysková 2;  M. Švarcová 3,4;  I. Kuklová 5;  R. Dobiáš 6,7;  N. Mallátová 8;  M. Kolařík 3;  V. Hubka 1,3
Authors‘ workplace: Laboratoř mykologie, oddělení lékařské mikrobiologie Praha a Kladno, Zdravotní ústav se sídlem v Ústí nad Labem, Praha, vedoucí oddělení Ing. Josef Čermák, Ph. D. 2;  Laboratoř genetiky a metabolismu hub, Mikrobiologický ústav, Akademie věd České republiky, Praha, vedoucí laboratoře doc. Mgr. Miroslav Kolařík, Ph. D. 3;  Katedra genetiky a mikrobiologie, Přírodovědecká fakulta, Univerzita Karlova, Praha, vedoucí katedry doc. RNDr. Ruth Tachezy, Ph. D. 4;  Dermatovenerologická klinika 1. lékařské fakulty Univerzity Karlovy a Všeobecné fakultní nemocnice, Praha, přednosta kliniky prof. MUDr. Jiří Štork, CSc. 5;  Oddělení bakteriologie a mykologie, Zdravotní ústav se sídlem v Ostravě, Ostrava, vedoucí oddělení Mgr. Eva Krejčí Ph. D. 6;  Ústav laboratorní biomedicíny, Ústav mikrobiologie, Lékařská fakulta, Ostravská univerzita, Ostrava, vedoucí ústavu prof. MUDr. David Stejskal, Ph. D., MBA 7;  Laboratoř parazitologie a mykologie, Centrální laboratoře, Nemocnice České Budějovice, ředitel centrálních laboratoří MUDr. Miroslav Verner 8
Published in: Čes-slov Derm, 99, 2024, No. 5, p. 200-208
Category: Pharmacologyand Therapy, Clinical Trials

Overview

Terbinafine, an allylamine antifungal agent, is the drug of first choice in the systemic treatment of dermatophytoses. It inhibits the enzyme squalene epoxidase (SQLE), involved in the ergosterol biosynthetic pathway. The spread of terbinafine resistance in dermatophytes is a new challenge. The highest prevalence of resistance is described in India and Southeast Asia, but it is spreading globally. This study summarizes resistance data from around the world in Trichophyton rubrum and T. mentagrophytes species and compares them with data from the Czech Republic, including molecular mechanisms of resistance. Between 2020 and 2021, 514 strains of T. rubrum and 240 strains of T. mentagrophytes have been screened for resistance in the Czech Republic. Resistance was detected only in T. mentagrophytes with a prevalence of 2.5%. All resistant strains carried the F397L mutation in the SQLE gene and showed high minimum inhibitory concentrations to terbinafine (≥ 4 mg/L). Due to the relatively low prevalence of resistance, there is no need to change the current management of dermatophytoses in the Czech Republic, but continuous monitoring remains important.

Keywords:

allylamine antifungals – anthropophilic dermatophytes – antifungal resistance – dermatophytosis – squalene-epoxidase – Trichophyton mentagrophytes – Trichophyton rubrum – zoophilic dermatophytes

Sources
  1. ARENDRUP, M. C., JØRGENSEN, K. M., GUINEA, J. et al. Multicentre validation of a EUCAST method for the antifungal susceptibility testing of microconidia-forming dermatophytes. Journal of Antimicrobial Chemotherapy, 2020, 75, p. 1807–1819.
  2. ARENDRUP, M. C., KAHLMETER, G., GUINEA, J. et al. How to: perform antifungal susceptibility testing of microconidia-forming dermatophytes following the new reference EUCAST method E. Def 11.0, exemplified by Trichophyton. Clin Microbiol Infect, 2021, 27, p. 55–60.
  3. ASTVAD, K. M. T., HARE, R. K., JØRGENSEN, K. M. et al. Increasing terbinafine resistance in Danish Trichophyton isolates 2019–2020. J Fungi, 2022, 8, p. 150.
  4. BLANCHARD, G., AMAROV, B., FRATTI, M. et al. Reliable and rapid identification of terbinafine resistance in dermatophytic nail and skin infections. J Eur Acad Dermatol Venereol, 2023, 37, p. 2080–2089.
  5. BORTOLUZZI, P., PRIGITANO, A., SECHI, A. 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, p. 680–687.
  6. CAÑETE-GIBAS, C. F., MELE, J., PATTERSON, H. P. et al. Terbinafine-resistant dermatophytes and the presence of Trichophyton indotineae in North America. J Clin Microbiol, 2023, 61, p. e00562–23.
  7. DE HOOG, G. S., DUKIK, K., MONOD, M. et al. Toward a novel multilocus phylogenetic taxonomy for the dermatophytes. Mycopathologia, 2017, 182, p. 5–31.
  8. DE HOOG, G. S., GUARRO, J., GENÉ, J., AHMED, S., AL-HATMI, A. M. S., FIGUERAS, M. J., VITALE, R. G. Atlas of Clinical Fungi. 4th edition. Hilversum, The Netherlands, 2020. Hilversum.
  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, p. 73–76.
  2. DURDU, M., KANDEMIR, H., KARAKOYUN, A. S. et al. First terbinafine-resistant Trichophyton indotineae isolates with Phe397Leu and/or Thr414His mutations in Turkey. Mycopathologia, 2023, 188, p. 295–304.
  3. EBERT, A., MONOD, M., SALAMIN, K. et al. Alarming India‐wide phenomenon of antifungal resistance in dermatophytes: a multicentre study. Mycoses, 2020, 63, p. 717–728.
  4. GRÄSER, Y., KUIJPERS, A., PRESBER, W. et al. Molecular taxonomy of the Trichophyton rubrum complex. J Clin Microbiol, 2000, 38, p. 3329–3336.
  5. GU, D., HATCH, M., GHANNOUM, M. et al. Treatment-resistant dermatophytosis: A representative case highlighting an emerging public health threat. JAAD Case Reports, 2020, 6, p. 1153–1155.
  6. GUPTA, A. K., COOPER, E. A., WANG, T. et al. Detection of squalene epoxidase mutations in US onychomycosis patients: implications for management. J Invest Dermatol, 2023, 143, p. 2332–2334.
  7. GUPTA, A. K., TALUKDER, M., VENKATARAMAN, M. Review of the alternative therapies for onychomycosis and superficial fungal infections: posaconazole, fosravuconazole, voriconazole, oteseconazole. Int J Dermatol, 2022, 61, p. 1431–1441.
  8. HIRUMA, J., NOGUCHI, H., HASE, M. et al. Epidemiological study of terbinafine‐resistant dermatophytes isolated from Japanese patients. J Dermatol, 2021, 48, p. 564–567.
  9. HYDE, K. D., BALDRIAN, P., CHEN, Y. et al. Current trends, limitations and future research in the fungi? Fungal Divers, 2024, 125, p. 1–71.
  10. CHOLLET, A., CATTIN, V., FRATTI, M. et al. Which fungus originally was Trichophyton mentagrophytes? Historical review and illustration by a clinical case. Mycopathologia, 2015, 180, p. 1–5.
  11. JABET, A., BRUN, S., NORMAND, A.-C. et al. Extensive dermatophytosis caused by terbinafine-resistant Trichophyton indotineae, France. Emerg Infect Dis, 2022, 28, p. 229–233.
  12. KANO, R., KIMURA, U., KAKURAI, M. et al. Trichophyton indotineae sp. nov.: a new highly terbinafine-resistant anthropophilic dermatophyte species. Mycopathologia, 2020, 185, p. 947–958.
  13. KIMURA, U., HIRUMA, M., KANO, R. et al. Caution and warning: arrival of terbinafine‐resistant Trichophyton interdigitale of the Indian genotype, isolated from extensive dermatophytosis, in Japan. J Dermatol, 2020, 47, p. e192–e193.
  14. KLINGER, M., THEILER, M. 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, p. 1017–1025.
  15. KOLARCZYKOVÁ, D., LYSKOVÁ, P., ŠVARCOVÁ, M. et al. Terbinafine resistance in Trichophyton mentagrophytes and Trichophyton rubrum in the Czech Republic: A prospective multicentric study. Mycoses, 2024, 67, p. e13708.
  16. KONG, X., TANG, C., SINGH, 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, p. e00056–21.
  17. KUKLOVÁ, I. Onychomykózy. Remedia, 2016, 26, p. 242–245.
  18. ŁAGOWSKI, D., GNAT, S., NOWAKIEWICZ, A. et al. Intrinsic resistance to terbinafine among human and animal isolates of Trichophyton mentagrophytes related to amino acid substitution in the squalene epoxidase. Infection, 2020, 48, p. 889–897.
  19. LOCKHART, S. R., SMITH, D. J., GOLD, J. A. Trichophyton indotineae and other terbinafine-resistant dermatophytes in North America. J Clin Microbiol, 2023, 61, p. e00903–23.
  20. MANOYAN, M., SOKOLOV, V., GURSHEVA, A. et al.Sensitivity of isolated dermatophyte strains to antifungal drugs in the Russian Federation. J Fungi, 2019, 5, p. 95.
  21. MORENO-SABATER, A., NORMAND, A.-C., BIDAUD, A.-L. et al. Terbinafine resistance in dermatophytes: a French multicenter prospective study. J Fungi, 2022, 8, p. 220.
  22. MUKHERJEE, P. K., LEIDICH, S. D., ISHAM, N. et al. Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine. Antimicrob Agents Chemother, 2003, 47, p. 82–86.
  23. NENOFF, P., HERRMANN, J., GRÄSER, Y. Trichophyton mentagrophytes sive interdigitale? A dermatophyte in the course of time. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2007, 5, p. 198–202.
  24. NENOFF, P., VERMA, S. B., EBERT, A. et al. Spread of terbinafine-resistant Trichophyton mentagrophytes type VIII (India) in Germany –“the tip of the iceberg?”. J Fungi, 2020, 6, p. 207.
  25. OSBORNE, C. S., LEITNER, I., FAVRE, B. et al. Amino acid substitution in Trichophyton rubrum squalene epoxidase associated with resistance to terbinafine. Antimicrob Agents Chemother, 2005, 49, p. 2840–2844.
  26. POSSO-DE LOS RIOS, C. J., TADROS, E., SUMMER-BELL, R. C. et al. Terbinafine resistant Trichophyton indotineae isolated in patients with superficial dermatophyte infection in Canadian patients. J Cutan Med Surg, 2022, 26, p. 371–376.
  27. RYDER, N. Terbinafine: mode of action and properties of the squalene epoxidase inhibition. Br J Dermatol, 1992, 126, p. 2–7.
  28. SACHELI, R., HARAG, S., DEHAVAY, F. et al. Belgian national survey on tinea capitis: Epidemiological considerations and highlight of terbinafine-resistant T. mentagrophytes with a mutation on SQLE gene. J Fungi, 2020, 6, p. 195.
  1. SALEHI, Z., SHAMS-GHAHFAROKHI, M., RAZZAGHI-ABYANEH, M. Antifungal drug susceptibility profile of clinically important dermatophytes and determination of point mutations in terbinafine-resistant isolates. Eur J Clin Microbiol Infect Dis, 2018, 37, p. 1841–1846.
  2. SAUNTE, D. M., HARE, R. K., JØRGENSEN, K. M. et al. Emerging terbinafine resistance in Trichophyton: clinical characteristics, squalene epoxidase gene mutations, and a reliable EUCAST method for detection. Antimicrob Agents Chemother, 2019, 63, p. e01126–19.
  3. SHEN, J. J., ARENDRUP, M. C., VERMA, S. et al. The emerging terbinafine-resistant Trichophyton epidemic: What Is the role of antifungal susceptibility testing? Dermatology, 2022, 238, p. 60–79.
  4. SINGH, A., MASIH, A., KHURANA, A. et al. High terbinafine resistance in Trichophyton interdigitale isolates in Delhi, India harbouring mutations in the squalene epoxidase gene. Mycoses, 2018, 61, p. 477–484.
  5. SIOPI, M., EFSTATHIOU, I., THEODOROPOULOS, K. et al. Molecular epidemiology and antifungal susceptibility of Trichophyton isolates in Greece: emergence of terbinafine-resistant Trichophyton mentagrophytes type VIII locally and globally. J Fungi, 2021, 7, p. 419.
  6. ŠVARCOVÁ, M., VĚTROVSKÝ, T., KOLAŘÍK, M. et al. Defining the relationship between phylogeny, clinical manifestation, and phenotype for Trichophyton mentagrophytes/interdigitale complex; a literature review and taxonomic recommendations. Med Mycol, 2023, 61, p. myad042.
  7. TAGHIPOUR, S., SHAMSIZADEH, F., PCHELIN, I. M. et al. Emergence of terbinafine resistant Trichophyton mentagrophytes in Iran, harboring mutations in the squalene epoxidase (SQLE) gene. Infect Drug Resist, 2020, p. 845–850.
  8. UHRLAß, S., VERMA, S. B., GRÄSER, Y. et al. Trichophyton indotineae–An emerging pathogen causing recalcitrant dermatophytoses in India and worldwide – a multidimensional perspective. J Fungi, 2022, 8, p. 757.
  9. VERMA, S. B., VASANI, R. Male genital dermatophytosis–Clinical features and the effects of the misuse of topical steroids and steroid combinations– An alarming problem in India. Mycoses, 2016, 59, p. 606–614.
  10. YAMADA, T., MAEDA, M., ALSHAHNI, M. M. et al. Terbinafine resistance of Trichophyton clinical isolates caused by specific point mutations in the squalene epoxidase gene. Antimicrob Agents Chemother, 2017, 61, p. e00115–17.
  11. ZHANG, Y., RAO, R. Beyond ergosterol: linking pH to antifungal mechanisms. Virulence, 2010, 1, p. 551–554.
  12. ZONIOS, D. I., BENNETT, J. E. Update on azole antifungals. Published by Thieme Medical Publishers, 2008. 29 p. 198–210.

Poděkování

Studie byla podpořena projektem Ministerstva zdravotnictví ČR (grant NU2105-00681), projektem Strategie AV21 ‚VP33 Houby kolem nás i v nás‘ Akademie věd ČR a projektem dlouhodobého rozvoje výzkumu Akademie věd ČR (RVO: 61388971). Za pomoc s grafickými úpravami obrázků děkujeme Janu Karhanovi. Za pomoc v laboratoři děkujeme Lence Zídkové a Kateřině Glässnerové.

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Adresa pro korespondenci: MUDr. Mgr. Vít Hubka, Ph.D.
Katedra botaniky, Přírodovědecká fakulta UK
Benátská 2
128 00 Praha 2 e-mail: vit.hubka@gmail.com

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