Multidrug-resistant Trichophyton mentagrophytes genotype VIII in an Iranian family with generalized dermatophytosis: report of four cases and review of literature

doi:10.1111/ijd.15226

Review

. 2021 Jun;60(6):686-692.

doi: 10.1111/ijd.15226. Epub 2020 Oct 13.

Multidrug-resistant Trichophyton mentagrophytes genotype VIII in an Iranian family with generalized dermatophytosis: report of four cases and review of literature

Azam Fattahi¹, Fariba Shirvani², Azin Ayatollahi¹, Ali Rezaei-Matehkolaei³, Hamid Badali^{4

5}, Ensieh Lotfali⁶, Reza Ghasemi⁷, Zahra Pourpak⁸, Alireza Firooz¹

Affiliations

¹ Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran.
² Pediatric Infections Research Center, Research Institute for Children Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³ Department of Medical Mycology, School of Medicine, Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
⁴ Invasive Fungi Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
⁵ Fungus Testing Laboratory, Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
⁶ Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁷ Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁸ Immunology Asthma & Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

PMID: 33047849
DOI: 10.1111/ijd.15226

Review

Multidrug-resistant Trichophyton mentagrophytes genotype VIII in an Iranian family with generalized dermatophytosis: report of four cases and review of literature

Azam Fattahi et al. Int J Dermatol. 2021 Jun.

. 2021 Jun;60(6):686-692.

doi: 10.1111/ijd.15226. Epub 2020 Oct 13.

Authors

Azam Fattahi¹, Fariba Shirvani², Azin Ayatollahi¹, Ali Rezaei-Matehkolaei³, Hamid Badali^{4

5}, Ensieh Lotfali⁶, Reza Ghasemi⁷, Zahra Pourpak⁸, Alireza Firooz¹

Affiliations

¹ Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran.
² Pediatric Infections Research Center, Research Institute for Children Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³ Department of Medical Mycology, School of Medicine, Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
⁴ Invasive Fungi Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
⁵ Fungus Testing Laboratory, Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
⁶ Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁷ Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁸ Immunology Asthma & Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

PMID: 33047849
DOI: 10.1111/ijd.15226

Abstract

Background: The global spread of terbinafine-resistant Trichophyton mentagrophytes with point mutations in the squalene epoxidase (SQLE) gene is a big concern.

Aim: The present study presents a series of unusual familial cases of generalized dermatophytosis caused by multidrug-resistant T. mentagrophytes genotype VIII.

Methods: Initially, the skin samples of each patient were taken and then subjected to direct microscopy and culture in Mycosel Agar. The molecular identification of Trichophyton species (spp.) was performed for all family members. In addition, the immunologic tests were requested, and an antifungal susceptibility test was carried out using the broth microdilution protocol based on the Clinical and Laboratory Standards Institute M38, third edition. The SQLE gene for a terbinafine-resistant T. mentagrophytes genotype VIII was sequenced and confirmed its nucleotide sequence to KU242352 as a susceptible strain.

Results: Based on the results of mycological examination and ITS rDNA sequencing, the etiologic agent was identified as T. mentagrophytes as a zoophilic dermatophyte. This species showed multiple drug resistance in vitro against terbinafine (minimum inhibitory concentration (MICs ≥8 µg/ml), itraconazole (MIC ≥4), and fluconazole (MIC ≥16). The SQLE gene of the isolate was subjected to sequencing for mutation, which showed a point mutation as TTC/TTA in the gene leading to Phe397Leu amino acid substitution in the enzyme. Only one of the family members responded to itraconazole and was cured after the long-term use of itraconazole. Other family members were treated with oral voriconazole with no recurrence.

Conclusion: The transmission of this resistant T. mentagrophytes to other countries due to globalization is a serious issue to be considered.

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References

1. Taghipour S, Shamsizadeh F, Pchelin IM, 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.
1. Hambro CA, Yin NC, Yang C, et al. Trichophyton rubrum tinea capitis in an HIV-positive patient with generalized dermatophytosis. JAAD Case Rep 2017; 3: 19-21.
1. Marconi VC, Kradin R, Marty FM, et al. Disseminated dermatophytosis in a patient with hereditary hemochromatosis and hepatic cirrhosis: case report and review of the literature. Med Mycol 2010; 48: 518-527.
1. Lanternier F, Pathan S, Vincent QB, et al. Deep dermatophytosis and inherited CARD9 deficiency. N Engl J Med 2013; 369: 1704-1714.
1. Adimi P, Hashemi SJ, Mahmoudi M, et al. In-vitro activity of 10 antifungal agents against 320 dermatophyte strains using microdilution method in Tehran. Iran J Pharm Res: IJPR 2013; 12: 537-545.

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[1] Taghipour S, Shamsizadeh F, Pchelin IM, 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.

[2] Taghipour S, Shamsizadeh F, Pchelin IM, 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.

[3] Hambro CA, Yin NC, Yang C, et al. Trichophyton rubrum tinea capitis in an HIV-positive patient with generalized dermatophytosis. JAAD Case Rep 2017; 3: 19-21.

[4] Hambro CA, Yin NC, Yang C, et al. Trichophyton rubrum tinea capitis in an HIV-positive patient with generalized dermatophytosis. JAAD Case Rep 2017; 3: 19-21.

[5] Marconi VC, Kradin R, Marty FM, et al. Disseminated dermatophytosis in a patient with hereditary hemochromatosis and hepatic cirrhosis: case report and review of the literature. Med Mycol 2010; 48: 518-527.

[6] Marconi VC, Kradin R, Marty FM, et al. Disseminated dermatophytosis in a patient with hereditary hemochromatosis and hepatic cirrhosis: case report and review of the literature. Med Mycol 2010; 48: 518-527.

[7] Lanternier F, Pathan S, Vincent QB, et al. Deep dermatophytosis and inherited CARD9 deficiency. N Engl J Med 2013; 369: 1704-1714.

[8] Lanternier F, Pathan S, Vincent QB, et al. Deep dermatophytosis and inherited CARD9 deficiency. N Engl J Med 2013; 369: 1704-1714.

[9] Adimi P, Hashemi SJ, Mahmoudi M, et al. In-vitro activity of 10 antifungal agents against 320 dermatophyte strains using microdilution method in Tehran. Iran J Pharm Res: IJPR 2013; 12: 537-545.

[10] Adimi P, Hashemi SJ, Mahmoudi M, et al. In-vitro activity of 10 antifungal agents against 320 dermatophyte strains using microdilution method in Tehran. Iran J Pharm Res: IJPR 2013; 12: 537-545.

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Multidrug-resistant Trichophyton mentagrophytes genotype VIII in an Iranian family with generalized dermatophytosis: report of four cases and review of literature

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Multidrug-resistant Trichophyton mentagrophytes genotype VIII in an Iranian family with generalized dermatophytosis: report of four cases and review of literature

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