Increasing Terbinafine Resistance in Danish Trichophyton Isolates 2019–2020
Abstract
:1. Introduction
2. Materials and Methods
2.1. Inclusion Criteria and Methods for Culture and Identification
2.2. Antifungal Susceptibility Testing
2.3. SQLE Sequencing
3. Results
3.1. Isolates and Identification
3.2. Antifungal Susceptibility Testing
3.3. SQLE sequencing
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- De Hoog, G.S.; Dukik, K.; Monod, M.; Packeu, A.; Stubbe, D.; Hendrickx, M.; Kupsch, C.; Stielow, J.B.; Freeke, J.; Göker, M.; et al. Toward a Novel Multilocus Phylogenetic Taxonomy for the Dermatophytes. Mycopathologia 2017, 182, 5–31. [Google Scholar] [CrossRef]
- Kano, R.; Kimura, U.; Kakurai, M.; Hiruma, J.; Kamata, H.; Suga, Y.; Harada, K. Trichophyton indotineae sp. nov.: A New Highly Terbinafine-Resistant Anthropophilic Dermatophyte Species. Mycopathologia 2020, 185, 947–958. [Google Scholar] [CrossRef] [PubMed]
- Tang, C.; Kong, X.; Ahmed, S.A.; Thakur, R.; Chowdhary, A.; Nenoff, P.; Uhrlass, S.; Verma, S.B.; Meis, J.F.; Kandemir, H.; et al. Taxonomy of the Trichophyton mentagrophytes/T. interdigitale Species Complex Harboring the Highly Virulent, Multiresistant Genotype T. indotineae. Mycopathologia 2021, 186, 315–326. [Google Scholar] [CrossRef]
- Saunte, D.M.; Arendrup, M.C. Månedsbladet Rationel Farmakoterapi 2015, nr. 3. Svampeinfektioner i Hud, Hår og Negle. Available online: https://www.sst.dk/da/udgivelser/2015/rationel-farmakoterapi-3-2015/svampeinfektioner-i-hud-haar-og-negle (accessed on 16 December 2021).
- Khurana, A.; Sardana, K.; Chowdhary, A. Antifungal resistance ina dermatophytes: Recent trends and therapeutic implications. Fungal Genet. Biol. 2019, 132, 103255. [Google Scholar] [CrossRef]
- Saunte, D.M.L.L.; Hare, R.K.; Jørgensen, K.M.; Jørgensen, R.; Deleuran, M.; Zachariae, C.O.; Thomsen, S.F.; Bjørnskov-Halkier, L.; Kofoed, K.; Arendrup, M.C. Emerging Terbinafine Resistance in Trichophyton: Clinical Characteristics, Squalene Epoxidase Gene Mutations, and a Reliable EUCAST Method for Detection. Antimicrob. Agents Chemother. 2019, 63, e01126-19. [Google Scholar] [CrossRef] [PubMed]
- Schøsler, L.; Andersen, L.K.; Arendrup, M.C.; Sommerlund, M. Recurrent terbinafine resistant Trichophyton rubrum infection in a child with congenital ichthyosis. Pediatr. Dermatol. 2018, 35, 259–260. [Google Scholar] [CrossRef] [PubMed]
- Digby, S.; Hald, M.; Arendrup, M.; Hjort, S.; Kofoed, K. Darier Disease Complicated by Terbinafine-resistant Trichophyton rubrum: A Case Report. Acta Derm. Venereol. 2017, 97, 139–140. [Google Scholar] [CrossRef]
- Yamada, T.; Maeda, M.; Alshahni, M.M.; Tanaka, R.; Yaguchi, T.; Bontems, O.; Salamin, K.; Fratti, M.; Monod, M. Terbinafine resistance of Trichophyton clinical isolates caused by specific point mutations in the squalene epoxidase gene. Antimicrob. Agents Chemother. 2017, 61, e00115-17. [Google Scholar] [CrossRef]
- Saunte, D.M.L.; Pereiro-Ferreirós, M.; Rodríguez-Cerdeira, C.; Sergeev, A.Y.; Arabatzis, M.; Prohić, A.; Piraccini, B.M.; Lecerf, P.; Nenoff, P.; Kotrekhova, L.P.; et al. Emerging antifungal treatment failure of dermatophytosis in Europe: Take care or it may become endemic. J. Eur. Acad. Dermatol. Venereol. 2021, 35, 1582–1586. [Google Scholar] [CrossRef] [PubMed]
- Singh, A.; Masih, A.; Khurana, A.; Singh, P.K.; Gupta, M.; Hagen, F.; Meis, J.F.; Chowdhary, A. High terbinafine resistance in Trichophyton interdigitale isolates in Delhi, India harbouring mutations in the squalene epoxidase gene. Mycoses 2018, 61, 477–484. [Google Scholar] [CrossRef]
- Rudramurthy, S.M.; Shankarnarayan, S.A.; Dogra, S.; Shaw, D.; Mushtaq, K.; Paul, R.A.; Narang, T.; Chakrabarti, A. Mutation in the Squalene Epoxidase Gene of Trichophyton interdigitale and Trichophyton rubrum Associated with Allylamine Resistance. Antimicrob. Agents Chemother. 2018, 62, e02522-17. [Google Scholar] [CrossRef]
- 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, 63, 717–728. [Google Scholar] [CrossRef] [PubMed]
- Verma, S.B. Emergence of recalcitrant dermatophytosis in India. Lancet Infect. Dis. 2018, 18, 718–719. [Google Scholar] [CrossRef]
- Uhrlass, S.; Sithach, M.; Koch, D.; Wittig, F.; Muetze, H.; Krueger, C.N.P. Trichophyton mentagrophytes—A new genotype in Cambodia. J. Fungi 2019, 5, 460. [Google Scholar]
- Fattahi, A.; Shirvani, F.; Ayatollahi, A.; Rezaei-Matehkolaei, A.; Badali, H.; Lotfali, E.; Ghasemi, R.; Pourpak, Z.; Firooz, A. 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, 686–692. [Google Scholar] [CrossRef]
- Süß, A.; Uhrlaß, S.; Ludes, A.; Verma, S.B.; Monod, M.; Krüger, C.; Nenoff, P. Ausgeprägte Tinea corporis durch ein Terbinafin-resistentes Trichophyton-mentagrophytes-Isolat vom indischen Genotyp bei einem Säugling aus Bahrain in Deutschland. Der Hautarzt 2019, 70, 888–896. [Google Scholar] [CrossRef]
- Hsieh, A.; Quenan, S.; Riat, A.; Toutous-Trellu, L.; Fontao, L. A new mutation in the SQLE gene of Trichophyton mentagrophytes associated to terbinafine resistance in a couple with disseminated tinea corporis. J. Mycol. Med. 2019, 29, 352–355. [Google Scholar] [CrossRef]
- Siopi, M.; Efstathiou, I.; Theodoropoulos, K.; Pournaras, S.; Meletiadis, J.; Arikan-Akdagli, S. 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, 419. [Google Scholar] [CrossRef]
- Järv, H.; Uhrlaß, S.; Simkin, T.; Nenoff, P.; Alvarado Ramirez, E.; Chryssanthou, E.; Monod, M. Terbinafine resistant Trichophyton mentagrophytes genotype VIII, Indian type, isolated in Finland. J. Fungi 2019, 5, 39. [Google Scholar]
- Nenoff, P.; Verma, S.B.; 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 2020, 6, 207. [Google Scholar] [CrossRef] [PubMed]
- Nenoff, P.; Verma, S.B.; 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. [Google Scholar] [CrossRef] [PubMed]
- Sacheli, R.; Harag, S.; Dehavay, F.; Evrard, S.; Rousseaux, D.; Adjetey, A.; Seidel, L.; Laffineur, K.; Lagrou, K.; Hayette, M.P. 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, 195. [Google Scholar] [CrossRef] [PubMed]
- Łagowski, D.; Gnat, S.; Nowakiewicz, A.; Osińska, M.; Dyląg, M. Intrinsic resistance to terbinafine among human and animal isolates of Trichophyton mentagrophytes related to amino acid substitution in the squalene epoxidase. Infection 2020, 48, 889–897. [Google Scholar] [CrossRef]
- Manoyan, M.; Sokolov, V.; Gursheva, A.; Gabuzyan, N.; Panin, A.N. Sensitivity of isolated dermatophyte strains to antifungal drugs in the Russian Federation. J. Fungi 2019, 5, 95. [Google Scholar]
- Arendrup, M.C.; Kahlmeter, G.; Guinea, J.; Meletiadis, J. 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, 55–60. [Google Scholar] [CrossRef] [PubMed]
- Arendrup, M.C.; Jørgensen, K.M.; Guinea, J.; Lagrou, K.; Chryssanthou, E.; Hayette, M.-P.P.; Barchiesi, F.; Lass-Flörl, C.; Hamal, P.; Dannaoui, E.; et al. Multicentre validation of a EUCAST method for the antifungal susceptibility testing of microconidia-forming dermatophytes. J. Antimicrob. Chemother. 2020, 75, 1807–1819. [Google Scholar] [CrossRef]
- Arendrup, M.C.; Jørgensen, K.M.; Guinea, J.; Lagrou, K.; Chryssanthou, E.; Hayette, M.-P.; Barhciesi, F.; Lass-Flörl, C.; Hamal, P.; Dannaoui, E.; et al. Comment on: Multicentre validation of a EUCAST method for the antifungal susceptibility testing of microconidia-forming dermatophytes. J. Antimicrob. Chemother. 2022. online ahead of press. [Google Scholar] [CrossRef]
- Arendrup, M.C.; Jørgensen, K.M.; Hanemaaijer, N.; Verweij, P.E. ISO standard 20776-1 or serial 2-fold dilution for antifungal susceptibility plate preparation: That is the question! J. Antimicrob. Chemother. 2021, 76, 1793–1799. [Google Scholar] [CrossRef]
- The European Committee on Antimicrobial Susceptibility Testing. Routine and Extended Internal Quality Control for MIC Determination and Agar Dilution for Yeasts, Moulds and Dermatophytes as Recommended by EUCAST. Version 5.0, 2020. Available online: http://www.eucast.org (accessed on 1 December 2021).
- Saunte, D.M.; Svejgaard, E.L.; Hædersdal, M.; Frimodt-Møller, N.; Jensen, A.M.; Arendrup, M.C. Laboratory-based survey of dermatophyte infections in Denmark over a 10-year period. Acta Derm. Venereol. 2008, 88, 614–616. [Google Scholar] [CrossRef]
- Shaw, D.; Singh, S.; Dogra, S.; Jayaraman, J.; Bhat, R.; Panda, S.; Chakrabarti, A.; Anjum, N.; Chowdappa, A.; Nagamoti, M.; et al. MIC and Upper Limit of Wild-Type Distribution for 13 Antifungal Agents against a Trichophyton mentagrophytes-Trichophyton interdigitale Complex of Indian Origin. Antimicrob. Agents Chemother. 2020, 64, e01964-19. [Google Scholar] [CrossRef]
- Kong, X.; Tang, C.; Singh, A.; Ahmed, S.A.; Al-Hatmi, A.M.S.S.; Chowdhary, A.; Nenoff, P.; Gräser, Y.; Hainsworth, S.; Zhan, P.; et al. Antifungal Susceptibility and Mutations in the Squalene Epoxidase Gene in Dermatophytes of the Trichophyton mentagrophytes Species Complex. Antimicrob. Agents Chemother. 2021, 65, e00056-21. [Google Scholar] [CrossRef]
- Gnat, S.; Łagowski, D.; Nowakiewicz, A.; Dyląg, M.; Osińska, M. Complementary effect of mechanism of multidrug resistance in Trichophyton mentagrophytes isolated from human dermatophytoses of animal origin. Mycoses 2021, 64, 537–549. [Google Scholar] [CrossRef]
- Monod, M.; Feuermann, M.; Salamin, K.; Fratti, M.; Makino, M.; Alshahni, M.M.; Makimura, K.; Yamada, T. Trichophyton rubrum Azole Resistance Mediated by a New ABC Transporter, TruMDR3. Antimicrob. Agents Chemother. 2019, 63, e00863-19. [Google Scholar] [CrossRef]
- Burmester, A.; Hipler, U.C.; 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. [Google Scholar] [CrossRef] [PubMed]
- Singh, A.; Masih, A.; Monroy-Nieto, J.; Singh, P.K.; Bowers, J.; Travis, J.; Khurana, A.; Engelthaler, D.M.; Meis, J.F.; Chowdhary, A. 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. [Google Scholar] [CrossRef] [PubMed]
- Kano, R. Atp-binding cassette (Abc) transporter proteins in highly terbinafine-resistant strains of trichophyton indotineae (former species name: Trichophyton interdigitale). Med. Mycol. J. 2021, 62, 21–25. [Google Scholar] [CrossRef] [PubMed]
- Fachin, A.L.; Ferreira-Nozawa, M.S.; Maccheroni, W.; Martinez-Rossi, N.M. Role of the ABC transporter TruMDR2 in terbinafine, 4-nitroquinoline N-oxide and ethidium bromide susceptibility in Trichophyton rubrum. J. Med. Microbiol. 2006, 55, 1093–1099. [Google Scholar] [CrossRef] [PubMed]
- Taghipour, S.; Shamsizadeh, F.; Pchelin, I.M.; Rezaei-Matehhkolaei, A.; Mahmoudabadi, A.Z.; Valadan, R.; Ansari, S.; Katiraee, F.; Pakshir, K.; Zomorodian, K.; 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. [Google Scholar] [CrossRef]
- Saunte, D.M.L.; Hald, M.; Lindskov, R.; Foged, E.K.; Svejgaard, E.L.; Arendrup, M.C. Guidelines for Superficielle Svampeinfektioner Version 2. 2012. Available online: https://dds.nu/retningslinjer/ (accessed on 1 December 2021).
- Klinger, M.; Theiler, M.; Bosshard, P.P. Epidemiological and clinical aspects of Trichophyton mentagrophytes/Trichophyton interdigitale infections in the Zurich area: A retrospective study using genotyping. J. Eur. Acad. Dermatology Venereol. 2021, 35, 1017–1025. [Google Scholar] [CrossRef]
Number per Year (in % of Total) | |||
---|---|---|---|
2019 | 2020 | 2019–2020 | |
Patients | 16 | 43 | 59 |
T. rubrum | 13 | 35 | 48 (81.4%) |
T. indotineae | 2 | 4 | 6 (10.2%) |
T. interdigitale | 1 | 3 | 4 (6.8%) |
T. benhamiae | 1 | 1 (1.7%) | |
Isolates | 19 | 44 | 63 |
T. rubrum | 16 | 35 | 51 (81.0%) |
T. indotineae | 2 | 5 | 7 (11.1%) |
T. interdigitale | 1 | 3 | 4 (6.3%) |
T. benhamiae | 1 | 1 (1.6%) |
Species | Drug | MICs (mg/L) | MICs (n) | Modal | MIC90 | Range | %>tECOFF | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
≤0.004 | 0.008 | 0.016 | 0.03 | 0.06 | 0.125 | 0.25 | 0.5 | 1 | 2 | 4 | > 4 | ND | |||||||
T. rubrum | TERB | 1 | 3 | 8 | 7 | 1 | 2 | 7 | 4 | 1 | 6 | 3 | 8 | 43 | ND | ND | ≤0.004–>4 | 55.8 | |
n = 51 | ITRA | 9 | 8 | 14 | 9 | 2 | 1 | 1 | 7 | 44 | 0.06 | 0.125 | ≤0.016–4 | 4.5 | |||||
VOR | 2 | 7 | 20 | 13 | 2 | 7 | 44 | 0.06 | 0.125 | ≤0.016–0.25 | 4.5 | ||||||||
ISCO | 9 | 11 | 17 | 5 | 9 | 42 | 0.06 | 0.125 | ≤0.016–0.125 | ||||||||||
POS | 4 | 11 | 15 | 12 | 2 | 7 | 44 | 0.06 | 0.125 | 0.016–0.25 | |||||||||
OLO | 3 | 5 | 18 | 13 | 3 | 9 | 42 | 0.016 | 0.03 | 0.004–0.06 | |||||||||
0 | |||||||||||||||||||
T. indotineae | TERB | 2 | 3 | 2 | 7 | 4 | ND | 2–>4 | 100 | ||||||||||
n = 7 | ITRA | 4 | 2 | 1 | 7 | 0.016 | ND | ≤0.016–0.06 | 0 | ||||||||||
VOR | 1 | 3 | 2 | 1 | 7 | 0.125 | ND | 0.06–0.5 | 0 | ||||||||||
ISCO | 1 | 2 | 2 | 2 | 7 | ND | ND | 0.06–0.5 | |||||||||||
POS | 1 | 3 | 1 | 1 | 1 | 7 | 0.016 | ND | 0.008–0.125 | ||||||||||
OLO | 2 | 3 | 1 | 1 | 6 | 0.016 | ND | 0.008–0.03 | |||||||||||
T. interdigitale | TERB | 1 | 1 | 2 | 4 | ND | ND | ≤0.004–0.016 | 0 | ||||||||||
n = 4 | ITRA | 2 | 1 | 1 | 4 | ND | ND | ≤0.016–0.06 | 0 | ||||||||||
VOR | 2 | 1 | 1 | 4 | ND | ND | 0.06–0.25 | 0 | |||||||||||
ISCO | 1 | 1 | 1 | 1 | 4 | ND | ND | ≤0.016–0.06 | |||||||||||
POS | 3 | 1 | 4 | ND | ND | 0.03–0.06 | |||||||||||||
OLO | 3 | 1 | 4 | ND | ND | 0.008–0.016 |
Species | SQLE Profile (Genbank Accession) | MIC (mg/L) | N | % NWT /SQLE | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
≤0.004 | 0.008 | 0.016 | 0.03 | 0.06 | 0.125 | 0.25 | 0.5 | 1 | 2 | 4 | >4 | NP | ||||
T. rubrum | F397L (OM313306/OM313307) | 1 | 2 | 1 | 6 | 1 | 3 | 14 | 60.8 | |||||||
F397I (OM313305) | 1 | 1 | 2 | |||||||||||||
L393F (OM313304) | 2 | 2 | ||||||||||||||
L393S (OM313303) | 2 | 5 | 7 | |||||||||||||
Y414C/L438C (OM313302) | 1 | 1 | ||||||||||||||
F415S (OM313301) | 1 | 1 | ||||||||||||||
F415V (OM313300) | 1 | 1 | ||||||||||||||
L437P (OM313299) | 1 | 1 | ||||||||||||||
H440Y (OM313298) | 1 | 1 | ||||||||||||||
I479V (OM313297) | 1 | 1 | ||||||||||||||
WT (OM313296) | 1 | 3 | 7 | 6 | 1 | 2 | 20 | |||||||||
T. indotineae | F397L (OM313310/ OM313311) | 2 | 2 | 1 | 5 | 63.6 | ||||||||||
L393F (OM313308) | 1 | 1 | ||||||||||||||
F397L/A448T (OM313309) | 1 | 1 | ||||||||||||||
T. interdigitale | WT (OM313312) | 1 | 1 | 2 | 4 | |||||||||||
T. benhamiae | WT (OM313313) | 1 | 1 | 0 | ||||||||||||
Trichophyton spp. | Total | 2 | 4 | 11 | 7 | 1 | 2 | 7 | 4 | 3 | 9 | 5 | 8 | 63 | 60.3 |
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Astvad, K.M.T.; Hare, R.K.; Jørgensen, K.M.; Saunte, D.M.L.; Thomsen, P.K.; Arendrup, M.C. Increasing Terbinafine Resistance in Danish Trichophyton Isolates 2019–2020. J. Fungi 2022, 8, 150. https://0-doi-org.brum.beds.ac.uk/10.3390/jof8020150
Astvad KMT, Hare RK, Jørgensen KM, Saunte DML, Thomsen PK, Arendrup MC. Increasing Terbinafine Resistance in Danish Trichophyton Isolates 2019–2020. Journal of Fungi. 2022; 8(2):150. https://0-doi-org.brum.beds.ac.uk/10.3390/jof8020150
Chicago/Turabian StyleAstvad, Karen Marie Thyssen, Rasmus Krøger Hare, Karin Meinike Jørgensen, Ditte Marie Lindhardt Saunte, Philip Kjettinge Thomsen, and Maiken Cavling Arendrup. 2022. "Increasing Terbinafine Resistance in Danish Trichophyton Isolates 2019–2020" Journal of Fungi 8, no. 2: 150. https://0-doi-org.brum.beds.ac.uk/10.3390/jof8020150