Azam Fattahi1, Fariba Shirvani2, Azin Ayatollahi1, Ali Rezaei-Matehkolaei3, Hamid Badali4,5, Ensieh Lotfali6, Reza Ghasemi7, Zahra Pourpak8, Alireza Firooz1. 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.
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.
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.