Antifungal Resistance in Dermatophytes: Genetic considerations, Clinical Presentations and Alternative Therapies

SACHELI, Rosalie; HAYETTE, Marie-Pierre

doi:10.3390/jof7110983

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Antifungal Resistance in Dermatophytes: Genetic considerations, Clinical Presentations and Alternative Therapies

SACHELI, Rosalie; HAYETTE, Marie-Pierre

2021 • In Journal of Fungi

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https://hdl.handle.net/2268/265810

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10.3390/jof7110983

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Keywords :

dermatophytes; resistance; terbinafine

Abstract :

[en] Numerous reports describe the emergence of resistance in dermatophytes, especially in T. rubrum and T. mentagrophytes/indotineae strains. We here present a review of the current status of resistance in dermatophytes worldwide. Resistance to terbinafine is mainly discussed, with dif-ferent mutations found in the squalene epoxidase gene also considered. Resistance to azoles is also approached. Clinical presentations caused by resistant dermatophytes are presented, to-gether with alternative therapies that help to better manage these kind of infections.

Disciplines :

Microbiology

Author, co-author :

SACHELI, Rosalie ; Centre Hospitalier Universitaire de Liège - CHU > Unilab > Laboratoire CNR

HAYETTE, Marie-Pierre ; Centre Hospitalier Universitaire de Liège - CHU > Unilab > Service de microbiologie clinique

Language :

English

Title :

Antifungal Resistance in Dermatophytes: Genetic considerations, Clinical Presentations and Alternative Therapies

Publication date :

November 2021

Journal title :

Journal of Fungi

eISSN :

2309-608X

Publisher :

MDPI AG, Switzerland

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 07 December 2021

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Mukherjee, P.K.; Leidich, S.D.; Isham, N.; Leitner, I.; Ryder, N.S.; Ghannoum, M.A. Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine. Antimicrob. Agents Chemother. 2003, 47, 82–86. [CrossRef]
Favre, B.; Ghannoum, M.A.; Ryder, N.S. Biochemical characterization of terbinafine-resistant Trichophyton rubrum isolates. Med. Mycol. 2004, 42, 525–529. [CrossRef]
Osborne, C.S.; Leitner, I.; Favre, B.; Ryder, N.S. Amino acid substitution in Trichophyton rubrum squalene epoxidase associated with resistance to terbinafine. Antimicrob. Agents Chemother. 2005, 42, 525–529. [CrossRef] [PubMed]
Osborne, C.S.; Leitner, I.; Hofbauer, B.; Fielding, C.A.; Favre, B.; Ryder, N.S. Biological, biochemical, and molecular characterization of a new clinical Trichophyton rubrum isolate resistant to terbinafine. Antimicrob. Agents Chemother. 2006, 50, 2234–2236. [CrossRef] [PubMed]
Alipour, M.; Mozafari, N.A. Terbinafine susceptibility and genotypic heterogeneity in clinical isolates of Trichophyton mentagrophytes by random amplified polymorphic DNA (RAPD). J. Mycol. Med. 2015, 25, e1–e9. [CrossRef] [PubMed]
Chowdhary, A.; Singh, A.; Singh, P.K.; Khurana, A.; Meis, J.F. Perspectives on misidentification of Trichophyton interdigi-tale/Trichophyton mentagrophytes using internal transcribed spacer region sequencing: Urgent need to update the sequence database. Mycoses 2019, 62, 11–15. [CrossRef]
Kabarriti, R.; Brodin, N.P.; Maron, M.I.; Tomé, W.A.; Halmos, B.; Guha, C.; Kalnicki, S.; Garg, M.K.; Ohri, N. Reply to Chowdhary et al. Adv. Radiat. Oncol. 2020, 5, 713–714. [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. [CrossRef]
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. [CrossRef]
Verma, S.B.; Panda, S.; Nenoff, P.; Singal, A.; Rudramuruthy, S.M.; Uhrlass, S.; Das, A.; Bisherwal, K.; Shaw, D.; Vasani, R. The unprecedented epidemic-like scenario of dermatophytosis in India: I. Epidemiology, risk factors and clinical features. Indian J. Dermatol. Venereol. Leprol. 2021, 87, 154–175. [CrossRef]
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. [CrossRef] [PubMed]
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, 61, 477–484. [CrossRef] [PubMed]
Khurana, A.; Masih, A.; Chowdhary, A.; Sardana, K.; Borker, S.; Gupta, A.; Gautam, R.K.; Sharma, P.K.; Jain, D. 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. [CrossRef] [PubMed]
Burmester, A.; Hipler, U.C.; Hensche, R.; Elsner, P.; Wiegand, C. Point mutations in the squalene epoxidase gene of Indian ITS genotype VIII T. mentagrophytes identified after DNA isolation from infected scales. Med. Mycol. Case Rep. 2019, 26, 23–24. [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. [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. [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. [CrossRef]
Burmester, A.; Hipler, U.C.; Uhrlaß, S.; Nenoff, P.; Singal, A.; Verma, S.B.; Elsner, P.; Wiegand, C. Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance. Mycoses 2020, 63, 1175–1180. [CrossRef]
Shankarnarayan, S.A.; Shaw, D.; Sharma, A.; Chakrabarti, A.; Dogra, S.; Kumaran, M.S.; Kaur, H.; Ghosh, A.; Rudramurthy, S.M. Rapid detection of terbinafine resistance in Trichophyton species by Amplified refractory mutation system-polymerase chain reaction. Sci. Rep. 2020, 10, 1297. [CrossRef]
Gaurav, V.; Bhattacharya, S.N.; Sharma, N.; Datt, S.; Kumar, P.; Rai, G.; Singh, P.K.; Taneja, B.; Das, S. Terbinafine resistance in dermatophytes: Time to revisit alternate antifungal therapy. J. Med. Mycol. 2021, 31, 101087. [CrossRef] [PubMed]
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. [CrossRef] [PubMed]
Wingfield Digby, S.S.; Hald, M.; Arendrup, M.C.; Hjorth, S.V.; Kofoed, K. Darier disease complicated by terbinafine-resistant Trichophyton rubrum: A case report. Acta Derm. Venereol. 2017, 97, 139–140. [CrossRef]
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. [CrossRef]
Saunte, D.M.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. [CrossRef] [PubMed]
Süß, A.; Uhrlaß, S.; Ludes, A.; Verma, S.B.; Monod, M.; Krüger, C.; Nenoff, P. Extensive tinea corporis due to a terbinafine-resistant Trichophyton mentagrophytes isolate of the Indian genotype in a young infant from Bahrain in Germany. Hautarzt 2019, 70, 888–896. [CrossRef]
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. [CrossRef]
Łagowski, D.; Gnat, S.; Nowakiewicz, A.; Osińska, M.; Dylag,˛ 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. [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. [CrossRef]
Siopi, M.; Efstathiou, I.; Theodoropoulos, K.; Pournaras, S.; Meletiadis, J. 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. [CrossRef]
Suzuki, S.; Mano, Y.; Furuya, N.; Fujitani, K. Discovery of terbinafine low susceptibility trichophyton rubrum strain in Japan. Biocontrol Sci. 2018, 23, 151–154. [CrossRef]
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, 1841–1846. [CrossRef] [PubMed]
Hiruma, J.; Kitagawa, H.; Noguchi, H.; Kano, R.; Hiruma, M.; Kamata, H.; Harada, K. Terbinafine-resistant strain of Trichophyton interdigitale strain isolated from a tinea pedis patient. J. Dermatol. 2019, 46, 351–353. [CrossRef] [PubMed]
Noguchi, H.; Matsumoto, T.; Hiruma, M.; Kimura, U.; Kano, R.; Yaguchi, T.; Fukushima, S.; Ihn, H. Tinea unguium caused by terbinafine-resistant Trichophyton rubrum successfully treated with fosravuconazole. J. Dermatol. 2019, 46, e446–e447. [CrossRef]
Kakurai, M.; Harada, K.; Maeda, T.; Hiruma, J.; Kano, R.; Demitsu, T. Case of tinea corporis due to terbinafine-resistant Trichophyton interdigitale. J. Dermatol. 2020, 47, e104–e105. [CrossRef]
Kimura, U.; Hiruma, M.; Kano, R.; Matsumoto, T.; Noguchi, H.; Takamori, K.; Suga, Y. Caution and warning: Arrival of terbinafine-resistant Trichophyton interdigitale of the Indian genotype, isolated from extensive dermatophytosis, in Japan. J. Dermatol. 2020, 47, e192–e193. [CrossRef]
Hiruma, J.; Noguchi, H.; Hase, M.; Tokuhisa, Y.; Shimizu, T.; Ogawa, T.; Hiruma, M.; Harada, K.; Kano, R. Epidemiological study of terbinafine-resistant dermatophytes isolated from Japanese patients. J. Dermatol. 2021, 48, 564–567. [CrossRef]
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. [CrossRef]
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. [CrossRef]
Firooz, A.; Daneshpazhooh, M.; Lotfali, E.; Sharzad Kavkani, M.; Ghasemi, Z.; Khamesipoor, A.; Nassiri Kashani, M.; Miramin Mohammadi, A.; Skandari, S.E.; Ahmad Nasrollahi, S.; et al. Drug Sensitivity Profile of Fungi Isolated from Onychomycosis Patients and Evaluation of Squalene Epoxidase Mutation in One Terbinafine-Resistant Trichophyton mentagrophytes Species. Microb. Drug Resist. 2021. [CrossRef] [PubMed]
Kong, X.; Tang, C.; Singh, A.; Ahmed, S.A.; Al-Hatmi, A.M.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, AAC-00056. [CrossRef]
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. [CrossRef]
Gu, D.; Hatch, M.; Ghannoum, M.; Elewski, B.E. Treatment-resistant dermatophytosis: A representative case highlighting an emerging public health threat. JAAD Case Reports 2020, 6, 1153–1155. [CrossRef]
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. [CrossRef] [PubMed]
Appelt, L.; Nenoff, P.; Uhrlaß, S.; Krüger, C.; Kühn, P.; Eichhorn, K.; Buder, S.; Beissert, S.; Abraham, S.; Aschoff, R.; et al. Terbinafin-resistente Dermatophytosen und Onychomykose durch Trichophyton rubrum. Hautarzt 2021, 72, 868–877. [CrossRef]
Verma, S.; Madhu, R. The great Indian epidemic of superficial dermatophytosis: An appraisal. Indian J. Dermatol. 2017, 62, 227.
Shenoy, M.; Jayaraman, J. Epidemic of difficult-to-treat tinea in India: Current scenario, culprits, and curbing strategies. Arch. Med. Heal. Sci. 2019, 7, 112. [CrossRef]
Pathania, S.; Rudramurthy, S.M.; Narang, T.; Saikia, U.N.; Dogra, S. A prospective study of the epidemiological and clinical patterns of recurrent dermatophytosis at a tertiary care hospital in India. Indian J. Dermatol. Venereol. Leprol. 2018, 84. [CrossRef]
Shen, J.J.; Arendrup, M.C.; Verma, S.; Saunte, D.M.L. The Emerging Terbinafine-Resistant Trichophyton Epidemic: What Is the Role of Antifungal Susceptibility Testing? Dermatology 2021. [CrossRef] [PubMed]
Gawaz, A.; Nenoff, P.; Uhrlaß, S.; Schaller, M. Treatment of a terbinafine-resistant trichophyton mentagrophytes type VIII. Hautarzt 2021, 72, 900–904. [CrossRef]
Cervelatti, E.P.; Fachin, A.L.; Ferreira-Nozawa, M.S.; Martinez-Rossi, N.M. Molecular cloning and characterization of a novel ABC transporter gene in the human pathogen Trichophyton rubrum. Med. Mycol. 2006, 44, 141–147. [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. [CrossRef]
Yamada, T.; Yaguchi, T.; Tamura, T.; Pich, C.; Salamin, K.; Feuermann, M.; Monod, M. Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2. Mycoses 2021, 64, 936–946. [CrossRef] [PubMed]
Yamada, T.; Yaguchi, T.; Salamin, K.; Guenova, E.; Feuermann, M.; Monod, M. Mfs1, a pleiotropic transporter in dermatophytes that plays a key role in their intrinsic resistance to chloramphenicol and fluconazole. J. Fungi 2021, 7, 542. [CrossRef] [PubMed]
Martins, M.P.; Franceschini, A.C.C.; Jacob, T.R.; Rossi, A.; Martinez-Rossi, N.M. Compensatory expression of multidrug-resistance genes encoding ABC transporters in dermatophytes. J. Med. Microbiol. 2016, 65, 605–610. [CrossRef] [PubMed]
Kano, R.; Hsiao, Y.H.; Han, H.S.; Chen, C.; Hasegawa, A.; Kamata, H. Resistance Mechanism in a Terbinafine-Resistant Strain of Microsporum canis. Mycopathologia 2018, 183, 623–627. [CrossRef] [PubMed]
Salehi, Z.; Fatahi, N.; Taran, M.; Izadi, A.; Badali, H.; Hashemi, S.J.; Rezaie, S.; Daie Ghazvini, R.; Ghaffari, M.; Aala, F.; et al. Comparison of in vitro antifungal activity of novel triazoles with available antifungal agents against dermatophyte species caused tinea pedis. J. Mycol. Med. 2020, 30, 100935. [CrossRef]
Arendrup, M.C.; Kahlmeter, G.; Guinea, J.; Meletiadis, J.; Arendrup, M.C.; Meletiadis, J.; Guinea, J.; Kahlmeter, G.; Arikan-Akdagli, S.; Friberg, F.; 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, 55–60. [CrossRef]