scholarly journals MIC and Upper Limit of Wild-Type Distribution for 13 Antifungal Agents against a Trichophyton mentagrophytes-Trichophyton interdigitale Complex of Indian Origin

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Dipika Shaw ◽  
Shreya Singh ◽  
Sunil Dogra ◽  
Jyothi Jayaraman ◽  
Ramesh Bhat ◽  
...  
Keyword(s):  
Antifungal Susceptibility ◽  
Trichophyton Mentagrophytes ◽  
Squalene Epoxidase ◽  
Wild Type ◽  
Content Type ◽  
Ciclopirox Olamine ◽  
Trichophyton Interdigitale ◽  
Medical Centers ◽  
Upper Limit ◽  
Indian Origin

ABSTRACT Dermatophytosis due to the Trichophyton mentagrophytes-Trichophyton interdigitale complex is being increasingly reported across India. Reports of therapeutic failure have surfaced recently, but there are no clinical break points (CBP) or epidemiological cutoffs (ECVs) available to guide the treatment of dermatophytosis. In this study, a total of 498 isolates of the T. mentagrophytes-interdigitale complex were collected from six medical centers over a period of five years (2014 to 2018). Antifungal susceptibility testing of the isolates was carried out for itraconazole, fluconazole, ketoconazole, voriconazole, luliconazole, sertaconazole, miconazole, clotrimazole, terbinafine, amorolfine, naftifine, ciclopirox olamine, and griseofulvin. The MICs (in mg/liter) comprising >95% of the modeled populations were as follows: 0.06 for miconazole, luliconazole, and amorolfine; 0.25 for voriconazole; 0.5 for itraconazole, ketoconazole, and ciclopirox olamine; 1 for clotrimazole and sertaconazole; 8 for terbinafine; 16 for naftifine; 32 for fluconazole; and 64 for griseofulvin. A high percentage of isolates above the upper limit of the wild-type MIC (UL-WT) were observed for miconazole (29%), luliconazole (13.9%), terbinafine (11.4%), naftifine (5.2%), and voriconazole (4.8%), while they were low for itraconazole (0.2%). Since the MICs of itraconazole were low against the T. mentagrophytes-interdigitale complex, this could be considered the choice of first-line treatment. The F397L mutation in the squalene epoxidase (SE) gene was observed in 77.1% of isolates with a terbinafine MIC of ≥1 mg/liter, but no mutation was detected in isolates with a terbinafine MIC of <1 mg/liter. In the absence of CBPs, evaluation of the UL-WT may be beneficial for managing dermatophytosis and monitoring the emergence of isolates with reduced susceptibility.

scholarly journals Mutation in the Squalene Epoxidase Gene ofTrichophyton interdigitaleandTrichophyton rubrumAssociated with Allylamine Resistance

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Shivaprakash M. Rudramurthy ◽  
Shamanth A. Shankarnarayan ◽  
Sunil Dogra ◽  
Dipika Shaw ◽  
Khurram Mushtaq ◽  
...  
Keyword(s):  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Trichophyton Rubrum ◽  
Antifungal Susceptibility ◽  
Ergosterol Biosynthesis ◽  
Squalene Epoxidase ◽  
Biosynthesis Pathway ◽  
Wild Type ◽  
Content Type ◽  
Recent Attention

ABSTRACTDermatophytosis, the commonest superficial fungal infection, has gained recent attention due to its change of epidemiology and treatment failures. Despite the availability of several agents effective against dermatophytes, the incidences of chronic infection, reinfection, and treatment failures are on the rise.Trichophyton rubrumandTrichophyton interdigitaleare the two species most frequently identified among clinical isolates in India. Consecutive patients (n= 195) with suspected dermatophytosis during the second half of 2014 were included in this study. Patients were categorized into relapse and new cases according to standard definitions. Antifungal susceptibility testing of the isolatedTrichophytonspecies (n= 127) was carried out with 12 antifungal agents: fluconazole, voriconazole, itraconazole, ketoconazole, sertaconazole, clotrimazole, terbinafine, naftifine, amorolfine, ciclopirox olamine, griseofulvin, and luliconazole. The squalene epoxidase gene was evaluated for mutation (if any) in 15T. interdigitaleand 5T. rubrumisolates exhibiting high MICs for terbinafine. A T1189C mutation was observed in fourT. interdigitaleand twoT. rubrumisolates. This transition leads to the change of phenylalanine to leucine in the 397th position of the squalene epoxidase enzyme. In homology modeling the mutant residue was smaller than the wild type and positioned in the dominant site of squalene epoxidase during drug interaction, which may lead to a failure to block the ergosterol biosynthesis pathway by the antifungal drug.

scholarly journals Molecular Analysis of Resistance and Detection of Non-Wild-Type Strains Using Etest Epidemiological Cutoff Values for Amphotericin B and Echinocandins for Bloodstream Candida Infections from a Tertiary Hospital in Qatar

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Saad J. Taj-Aldeen ◽  
Husam Salah ◽  
Winder B. Perez ◽  
Muna Almaslamani ◽  
Mary Motyl ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Hot Spot ◽  
Antifungal Susceptibility ◽  
Tertiary Hospital ◽  
Wild Type ◽  
Content Type ◽  
Cutoff Values ◽  
Echinocandin Resistance ◽  
Candida Infections ◽  
Type Strains

ABSTRACT A total of 301 Candida bloodstream isolates collected from 289 patients over 5 years at a tertiary hospital in Qatar were evaluated. Out of all Candida infections, 53% were diagnosed in patients admitted to the intensive care units. Steady increases in non-albicans Candida species were reported from 2009 to 2014 (30.2% for Candida albicans versus 69.8% for the other Candida species). Etest antifungal susceptibility testing was performed on all recovered clinical isolates to determine echinocandin (micafungin and anidulafungin) and amphotericin B susceptibilities and assess non-wild-type (non-WT) strains (strains for which MICs were above the epidemiological cutoff values). DNA sequence analysis was performed on all isolates to assess the presence of FKS mutations, which confer echinocandin resistance in Candida species. A total of 3.9% of isolates (12/301) among strains of C. albicans and C. orthopsilosis contained FKS hot spot mutations, including heterozygous mutations in FKS1. For C. tropicalis, the Etest appeared to overestimate strains non-WT for micafungin, anidulafungin, and amphotericin B, as 14%, 11%, and 35% of strains, respectively, had values above the epidemiological cutoff value. However, no FKS mutations were identified in this species. For all other species, micafungin best reported the echinocandin non-WT strains relative to the FKS genotype, as anidulafungin tended to overestimate non-wild-type strains. Besides C. tropicalis, few strains were classified as non-WT for amphotericin B.

scholarly journals Intrinsic resistance to terbinafine among human and animal isolates of Trichophyton mentagrophytes related to amino acid substitution in the squalene epoxidase

Infection ◽  
2020 ◽  
Vol 48 (6) ◽  
pp. 889-897 ◽  
Author(s):  
Dominik Łagowski ◽  
Sebastian Gnat ◽  
Aneta Nowakiewicz ◽  
Marcelina Osińska ◽  
Mariusz Dyląg
Keyword(s):  
Amino Acid ◽  
Fungal Infections ◽  
Single Point ◽  
Antifungal Susceptibility ◽  
Point Mutations ◽  
Trichophyton Mentagrophytes ◽  
Single Amino Acid ◽  
Squalene Epoxidase ◽  
Intrinsic Resistance ◽  
Resistant Strains

Abstract Background Dermatomycoses are the most common fungal infections in the world affecting a significant part of the human and animal population. The majority of zoophilic infections in humans are caused by Trichophyton mentagrophytes. Currently, the first-line drug for both oral and topical therapy is terbinafine. However, an increasing number of cases that are difficult to be cured with this drug have been noted in Europe and Asia. Resistance to terbinafine and other allylamines is very rare and usually correlated with point mutations in the squalene epoxidase gene resulting in single amino acid substitutions in the enzyme, which is crucial in the ergosterol synthesis pathway. Purpose Here, we report terbinafine-resistant T. mentagrophytes isolates among which one was an etiological factor of tinea capitis in a man and three were obtained from asymptomatic foxes in Poland. Methods We used the CLSI protocol to determine antifungal susceptibility profiles of naftifine, amphotericin B, griseofulvin, ketoconazole, miconazole, itraconazole, voriconazole, and ciclopirox. Moreover, the squalene epoxidase gene of the terbinafine-resistant strains was sequenced and analysed. Results In the genomes of all four resistant strains exhibiting elevated MICs to terbinafine (16 to 32 µg/ml), single-point mutations leading to Leu393Phe substitution in the squalene epoxidase enzyme were revealed. Among the other tested substances, a MIC50 value of 1 µg/ml was shown only for griseofulvin. Conclusion Finally, our study revealed that the terbinafine resistance phenomenon might not be acquired by exposure to the drug but can be intrinsic. This is evidenced by the description of the terbinafine-resistant strains isolated from the asymptomatic animals.

scholarly journals Emerging Terbinafine Resistance in Trichophyton: Clinical Characteristics, Squalene Epoxidase Gene Mutations, and a Reliable EUCAST Method for Detection

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Ditte M. L. Saunte ◽  
Rasmus K. Hare ◽  
Karin M. Jørgensen ◽  
René Jørgensen ◽  
Mette Deleuran ◽  
...  
Keyword(s):  
Homology Modeling ◽  
Susceptibility Testing ◽  
Topical Therapy ◽  
Antifungal Susceptibility ◽  
Acquired Resistance ◽  
Three Dimensional ◽  
Public Health Problem ◽  
Squalene Epoxidase ◽  
Content Type ◽  
The Mean

ABSTRACT In recent years, cases involving terbinafine-resistant Trichophyton isolates have been reported increasingly, particularly in India. We present 14 cases of terbinafine treatment failure in Trichophyton-infected Danish patients due to acquired resistance. Patients infected with Trichophyton rubrum (n = 12) or Trichophyton interdigitale (n = 2) with elevated terbinafine MICs during 2013–2018 were included. Antifungal susceptibility testing (AFST) was performed following a modified EUCAST E.Def 9.3.1 method (5 days of incubation) with or without cycloheximide and chloramphenicol (CC) supplementation of the growth medium. The squalene epoxidase (SE) target gene was sequenced, and 3-dimensional enzyme homology modeling was performed. Most patients (12/14 [86%]) were male. The mean age was 53.5 years (range, 11 to 77 years). The mean duration of infections was 4.8 years at the time of resistance detection. Prior systemic terbinafine treatment was documented for all patients, and topical therapy for 62% (information was missing in one case). Overall, nine isolates (64%) displayed high terbinafine resistance (MICs, 4 to >8 mg/liter), while two (14%) displayed moderate (MICs, 1 to 2 mg/liter) and three (21%) displayed low (MICs, 0.125 to 0.25 mg/liter) terbinafine resistance compared with control isolates. MICs generated with or without CC supplementation were similar, but CC prevented contamination. Known and novel SE amino acid substitutions (F397L, L393F, L393S, F415S, H440Y F484Y, and I121M V237I) were detected in resistant but not control isolates. Three-dimensional homology modeling suggested a role of the novel I121M and V237I alterations. Terbinafine resistance has been detected in Denmark using a modified EUCAST method, which facilitated susceptibility testing of dermatophytes. Action is needed for this emerging public health problem.

scholarly journals Biofilm Production and Antibiofilm Activity of Echinocandins and Liposomal Amphotericin B in Echinocandin-Resistant Yeast Species

2016 ◽  
Vol 60 (6) ◽  
pp. 3579-3586 ◽  
Author(s):  
Laura Judith Marcos-Zambrano ◽  
Marta Gómez-Perosanz ◽  
Pilar Escribano ◽  
Oscar Zaragoza ◽  
Emilio Bouza ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Metabolic Activity ◽  
Liposomal Amphotericin ◽  
Antifungal Susceptibility ◽  
Growth Control ◽  
Liposomal Amphotericin B ◽  
Antibiofilm Activity ◽  
Wild Type ◽  
Content Type ◽  
Type Strains

The echinocandins and liposomal amphotericin B are active against biofilm produced by echinocandin-susceptibleCandidastrains. However, few data have been reported on the production of biofilm by echinocandin-resistant isolates and their antifungal susceptibility. We studied the production of biofilm byfksmutantCandidastrains and intrinsically echinocandin-resistant non-Candidaisolates and the susceptibility of both entities to liposomal amphotericin B and echinocandins. We analyzed the production of biofilm by isolates from patients with fungemia (fksmutantCandida,n= 5; intrinsically echinocandin-resistant non-Candida,n= 12; andCandidawild type,n= 10). Biofilm formation was measured to classify strains according to biomass (crystal violet assay) and metabolic activity (XTT reduction assay). Preformed biofilms were tested against liposomal amphotericin B, caspofungin, micafungin, and anidulafungin. The sessile MIC was defined as the antifungal concentration yielding a 50% or 80% reduction in the metabolic activity of the biofilm compared to that of the growth control (SMIC50and SMIC80, respectively).fksmutantCandidaisolates formed biofilms in a fashion similar to that ofCandidawild-type strains. The echinocandins had the highest activity against biofilms formed by wild-typeCandidaisolates, followed byfksmutantCandidaisolates and non-Candidaisolates. Liposomal amphotericin B had the highest activity againstfksmutantCandidabiofilms. The formation of biofilm by echinocandin-resistant strains was similar to that of wild-type strains, although resistance to echinocandins remained high.

scholarly journals In VitroActivity of Isavuconazole against Opportunistic Fungal Pathogens from Two Mycology Reference Laboratories

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Michael A. Pfaller ◽  
Paul R. Rhomberg ◽  
Nathan P. Wiederhold ◽  
Connie Gibas ◽  
Carmita Sanders ◽  
...  
Keyword(s):  
Species Complex ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Wild Type ◽  
Content Type ◽  
Excellent Activity ◽  
Comparable Activity ◽  
Yeasts And Molds ◽  
Susceptibility Patterns

ABSTRACTMonitoring antifungal susceptibility patterns for new and established antifungal agents seems prudent given the increasing prevalence of uncommon species associated with higher antifungal resistance. We evaluated the activity of isavuconazole against 4,856 invasive yeasts and molds collected worldwide. The 4,856 clinical fungal isolates, including 2,351Candidaspecies isolates, 97 non-Candidayeasts, 1,972Aspergillusspecies isolates, and 361 non-Aspergillusmolds, including 292Mucoralesisolates collected in 2015 to 2016, were tested using CLSI methods. The MIC values for isavuconazole versusAspergillusranged from 0.06 to ≥16 μg/ml. The modal MIC for isavuconazole was 0.5 μg/ml (range, 0.25 [A. nidulansandA. terreusspecies complex] to 4 μg/ml [A. calidoustusandA. tubingensis]). EightA. fumigatusisolates had elevated isavuconazole MIC values at ≥8 μg/ml (non-wild type). Isavuconazole showed comparable activity to itraconazole against theMucorales. The lowest modal isavuconazole MIC values were seen forRhizopusspp.,R. arrhizusvar.arrhizus, andR. microsporus(all 1 μg/ml).Candidaspecies isolates were inhibited by ≤0.25 μg/ml of isavuconazole (range, 96.1% [C. lusitaniae] to 100.0% [C. albicans,C. dubliniensis,C. kefyr, andC. orthopsilosis]). MIC values were ≤1 μg/ml for 95.5% ofC. glabrataisolates and 100.0% ofC. kruseiisolates. Isavuconazole was active against the non-Candidayeasts, includingCryptococcus neoformans(100.0% at ≤0.5 μg/ml). Isavuconazole exhibited excellent activity against most species ofCandidaandAspergillus. Isavuconazole was comparable to posaconazole and voriconazole against the less common yeasts and molds. Isavuconazole was generally less active than posaconazole and more active than voriconazole against the 292Mucoralesisolates. We confirm the potentially useful activity of isavuconazole against species ofRhizopusas determined by CLSI methods.

scholarly journals Antifungal Susceptibility Testing of Aspergillus spp. by Using a Composite Correlation Index (CCI)-Based Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Method Appears To Not Offer Benefit over Traditional Broth Microdilution Testing

2017 ◽  
Vol 55 (7) ◽  
pp. 2030-2034 ◽  
Author(s):  
Melissa R. Gitman ◽  
Lisa McTaggart ◽  
Joanna Spinato ◽  
Rahgavi Poopalarajah ◽  
Erin Lister ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Laser Desorption Ionization ◽  
Wild Type ◽  
Ionization Time ◽  
Content Type ◽  
Maldi Tof Ms ◽  
Maldi Tof ◽  
Flight Mass Spectrometry ◽  
Tof Ms

ABSTRACT Aspergillus spp. cause serious invasive lung infections, and Aspergillus fumigatus is the most commonly encountered clinically significant species. Voriconazole is considered to be the drug of choice for treating A. fumigatus infections; however, rising resistance rates have been reported. We evaluated a matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS)-based method for the differentiation between wild-type and non-wild-type isolates of 20 Aspergillus spp. (including 2 isolates of Aspergillus ustus and 1 of Aspergillus calidoustus that were used as controls due their intrinsic low azole susceptibility with respect to the in vitro response to voriconazole). At 30 and 48 h of incubation, there was complete agreement between Cyp51A sequence analysis, broth microdilution, and MALDI-TOF MS classification of isolates as wild type or non-wild type. In this proof-of-concept study, we demonstrated that MALDI-TOF MS can be used to accurately detect A. fumigatus strains with reduced voriconazole susceptibility. However, rather than proving to be a rapid and simple method for antifungal susceptibility testing, this particular MS-based method showed no benefit over conventional testing methods.

scholarly journals cyp51A Mutations, Extrolite Profiles, and Antifungal Susceptibility in Clinical and Environmental Isolates of the Aspergillus viridinutans Species Complex

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Jessica J. Talbot ◽  
Jens C. Frisvad ◽  
Jacques F. Meis ◽  
Ferry Hagen ◽  
Paul E. Verweij ◽  
...  
Keyword(s):  
Species Complex ◽  
Antifungal Susceptibility ◽  
Gene Mutations ◽  
Azole Resistance ◽  
Wild Type ◽  
Environmental Isolates ◽  
Content Type ◽  
The Past ◽  
Agar Plug ◽  
Very High

ABSTRACT The past decade has seen an increase in aspergillosis in humans and animals due to Aspergillus viridinutans species complex members. Azole resistance is common to these infections, carrying a poor prognosis. cyp51A gene mutations are the main cause of acquired azole resistance in Aspergillus fumigatus. This study aimed to determine if the azole-resistant phenotype in A. viridinutans complex members is associated with cyp51A mutations or extrolite profiles. The cyp51A gene of clinical and environmental isolates was amplified using novel primers, antifungal susceptibility was tested using the Clinical and Laboratory Standards Institute methodology, and extrolite profiling was performed using agar plug extraction. Very high azole MICs were detected in 84% of the isolates (31/37). The MICs of the newer antifungals luliconazole and olorofim (F901318) were low for all isolates. cyp51A sequences revealed 113 nonsynonymous mutations compared to the sequence of wild-type A. fumigatus. M172A/V and D255G, previously associated with A. fumigatus azole resistance, were common among all isolates but were not correlated with azole MICs. Two environmental isolates with nonsusceptibility to itraconazole and high MICs of voriconazole and isavuconazole harbored G138C, previously associated with azole-resistant A. fumigatus. Some novel mutations were identified only among isolates with high azole MICs. However, cyp51A homology modeling did not cause a significant protein structure change for these mutations. There was no correlation between extrolite patterns and susceptibility. For A. viridinutans complex isolates, cyp51A mutations and the extrolites that they produced were not major causes of antifungal resistance. Luliconazole and olorofim show promise for treating azole-resistant infections caused by these cryptic species.

scholarly journals EUCAST Reference Testing of Rezafungin Susceptibility and Impact of Choice of Plastic Plates

2019 ◽  
Vol 63 (9) ◽  
Author(s):  
Maiken Cavling Arendrup ◽  
Karin Meinike Jørgensen ◽  
Rasmus Krøger Hare ◽  
Manuel Cuenca-Estrella ◽  
Oscar Zaragoza
Keyword(s):  
Antifungal Susceptibility ◽  
Reference Method ◽  
Wild Type ◽  
Phase 3 ◽  
Content Type ◽  
Microtiter Plates ◽  
The Difference ◽  
Long Acting ◽  
Interlaboratory Reproducibility ◽  
Type Strains

ABSTRACT Rezafungin is a new long-acting echinocandin currently in phase 3 development. Epidemiological cutoff values are necessary for breakpoint setting but have not been established due to unexplained interlaboratory MIC variations observed in a prior multicenter study. Here we investigated if the choice of microtiter plates affected the variability when anidulafungin was included as a comparator. Testing by the EUCAST E.Def 7.3.1 reference method using tissue and cell culture-treated polystyrene plates (TC plates) and untreated polystyrene plates (UT plates) from four manufacturers was performed. Six control strains (Candida albicans, n = 3; C. krusei, n = 2; C. parapsilosis, n = 1) were tested (520 MICs). Subsequently, 5 or 6 wild-type isolates and 4 or 5 fks mutants of C. albicans, C. glabrata, C. krusei, C. parapsilosis (wild type only), and C. tropicalis were tested (930 MICs). For each strain-plate combination, ≥98% of the repetitive MICs were within 3 dilutions. The rezafungin modal MICs for the collated C. albicans control strain distributions were 0.016 mg/liter across TC plates but 0.03 mg/liter across UT plates, whereas they were 0.004 mg/liter and 0.016 mg/liter, respectively, for anidulafungin. The difference was most pronounced with Falcon plates and was not observed for C. krusei and C. parapsilosis. Eleven rezafungin MICs for mutants overlapped with the MICs for wild-type isolates (TC plates, n = 4; UT plates, n = 7). For anidulafungin, five overlaps (all UT plates) were observed. Most overlaps (rezafungin, n = 5; anidulafungin, n = 3) were caused by fks mutants of C. tropicalis (Fks1, F650F/L) and C. glabrata (Fks2. D666Y; rezafungin, n = 2; anidulafungin, n = 1). Interlaboratory variation was low. The use of TC plates resulted in lower MICs, particularly for C. albicans and Falcon plates, ad this was more often the case for anidulafungin than for rezafungin. Adoption of TC plates for EUCAST antifungal susceptibility testing would improve interlaboratory reproducibility and the separation of non-wild-type and wild-type strains.

scholarly journals Antifungal susceptibility and mutations in the squalene epoxidase gene in dermatophytes of the Trichophyton mentagrophytes species complex

2021 ◽  
Author(s):  
Xue Kong ◽  
Chao Tang ◽  
Ashutosh Singh ◽  
Sarah A. Ahmed ◽  
Abdullah M.S. Al-Hatmi ◽  
...  
Keyword(s):  
Species Complex ◽  
Novel Species ◽  
Antifungal Susceptibility ◽  
Trichophyton Mentagrophytes ◽  
Squalene Epoxidase ◽  
Free Medium ◽  
Serial Transfer ◽  
The Past ◽  
Drug Free ◽  
High Mics

Background: During the past decade, a prolonged and serious outbreak of dermatophytosis due to a terbinafine-resistant novel species in the Trichophyton mentagrophytes/T. interdigitale complex is ongoing in India, and it spreads to several European countries. Objective: To investigate the molecular background of the squalene epoxidase (SQLE) gene in order to understand the risk of emergence and spread of multi-resistance in dermatophytes. Methods: Antifungal susceptibility for fluconazole, griseofulvin, itraconazole, ketoconazole, miconazole, naftifine, sertaconazole, and terbinafine was tested in 135 isolates from India, China, Australia, Germany and The Netherlands. Based on the latest taxonomic insights, strains were identified as three species: T. mentagrophytes s. str. (n=35), T. indotineae (n=64 representing the Indian clone) and T. interdigitale s. str. (n=36). Results: High minimum inhibitory concentrations (MICs) of terbinafine (>16 mg/L) were found in 34 (53%) T. indotineae isolates. These isolates showed an amino acid substitution in the 397th position of the SQLE gene. Elevated MICs of terbinafine (0.5 mg/L) were noted in 2 (3%) T. indotineae isolates; these isolates lead to Phe415Val and Leu393Ser of the SQLE gene. Stability of the effect of the mutations was proven by serial transfer on drug-free medium. Substitutions of Lys276Asn and Leu419Phe were found in susceptible T. mentagrophytes strains. The double mutant Phe377Leu/Ala448Thr showed higher MIC values for triazoles. Conclusions: High MICs of terbinafine are as yet limited to T. indotineae, and are unlikely to be distributed through the T. mentagrophytes species complex by genetic exchange.

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