Potential Sexual Transmission of Antifungal-Resistant Trichophyton indotineae.

We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.

Development of an agar-based screening method for terbinafine, itraconazole, and amorolfine susceptibility testing of Trichophyton spp.

Resistance in dermatophytes is an emerging global public health issue. We, therefore, developed an agar-based method for screening Trichophyton spp. susceptibility to terbinafine (TRB), itraconazole (ITC), and amorolfine (AMF) and validated it using molecularly characterized isolates. Α total of 40 Trichophyton spp. isolates, 28 TRB wild type (WT) (13 T. rubrum, 10 T. mentagrophytes, 5 T. interdigitale) and 12 TRB non-WT (7 T. rubrum, 5 T. indotineae) with different alterations in the squalene epoxidase (SQLE) gene, were used. The optimal test conditions (inoculum and drug concentrations, incubation time, and temperature) and stability over time were evaluated. The method was then applied for 86 WT Trichophyton spp. clinical isolates (68 T. rubrum, 7 T. interdigitale, 6 T. tonsurans, 5 T. mentagrophytes) and 4 non-WT T. indotineae. Optimal growth of drug-free controls was observed using an inoculum of 20 µL 0.5 McFarland after 5-7 days of incubation at 30°C. The optimal concentrations that prevented the growth of WT isolates were 0.016 mg/L of TRB, 1 mg/L of ITC, and 0.25 mg/L of AMF, whereas 0.125 mg/L of TRB was used for the detection of Trichophyton strong SQLE mutants (MIC ≥0.25 mg/L). The agar plates were stable up to 4 months. Inter-observer and inter-experimental agreement were 100%, and the method successfully detected TRB non-WT Trichophyton spp. strains showing 100% agreement with the reference EUCAST methodology. An agar-based method was developed for screening Trichophyton spp. in order to detect TRB non-WT weak and strong mutant isolates facilitating their detection in non-expert routine diagnostic laboratories.

Dual quantitative PCR assays for the rapid detection of Trichophyton indotineae from clinical samples.

Trichophyton indotineae is an emerging species of the Trichophyton mentagrophytes complex (TMC), responsible for an epidemic of widespread hairless skin infections that is frequently (50-70%) resistant to terbinafine. In order to initiate appropriate treatment as quickly as possible without waiting for culture positivity (10-15 days) and molecular identification from the strain, we developed a dual quantitative PCR (qPCR) for the direct detection of T. indotineae in clinical samples. We first designed a T. indotineae-specific qPCR assay (TI-qPCR) targeting a single specific polymorphism in the internal transcribed spacer region. Although none of the 94 non-dermatophyte and 7 dermatophyte species were amplified, this TI-qPCR allowed amplification of other TMC species at a lower yield. With equal amounts (0.1 ng) of DNA per reaction, the mean quantitative cycle (Cq) values for T. indotineae and non-indotineae TMC were 27.9 (±0.1) and 38.9 (±0.3), respectively. Therefore, we normalized this assay against a previously validated pan-dermatophyte qPCR assay (PD-qPCR) and relied on the ΔCq [(TI-qPCR) - (PD-qPCR)] to identify T. indotineae versus other TMC species. Dual assay was validated using 86 clinical samples of culture-confirmed T. indotinea and 19 non-indotineae TMC cases. The mean ΔCq for non-indotineae TMC was 9.6 ± 2.7, whereas the ΔCq for T. indotinea was -1.46 ± 2.1 (P < .001). Setting the ΔCq at 4.5 as a cutoff value resulted in 100% specificity for the detection of T. indotineae. This dual qPCR assay quickly detects T. indotineae from skin scrapings, aiding in early diagnosis and treatment for patients with suspected infection.

Identifying the emerging species Trichophyton indotineae is long and requires to wait for culture positivity. We developed a dual qPCR strategy to detect T. indotineae directly from clinical sample with a 100% sensitivity.

Whole genome characterization of Trichophyton indotineae isolated in Singapore.

Complete genome sequences from two Trichophyton indotineae isolates were obtained from a 23-year-old male presenting with tinea cruris after an overseas recreational water exposure and from a 53-year-old female patient with unknown travel history. Analysis of the squalene epoxidase gene and the cyp51 gene family showed an absence of mutations, correlating with phenotypic drug susceptibility. The Single Nucleotide Polymorphisms (SNPs) distance between both isolates was 92. Within the T. indotineae cluster, SNPs ranged from 7 to 182, suggesting a high genetic relatedness with other South Asian isolates. This study suggests that the prevalence of T. indotineae is under-reported and more widespread than previously thought.

Trichophyton indotineae, is a fungus causing difficult to treat ringworm infections. Two isolates were sequenced and their relationship and to other isolates was characterized. We also studied the genes responsible for first-line antifungal treatment.

Epidemiology and management of tinea capitis in France: A 6-year nationwide retrospective survey.

Tinea capitis (TC) is still a frequent dermatophytosis in France, both autochthonous and imported. A nationwide retrospective survey was performed and a total of 4395 TC cases were recorded within 36 French mycology laboratories during a 6-year period. TC is a disease that occurs in childhood with 85% of the cases occurring before 10 years old and 94% before the age of 15. Anthropophilic origin was predominant with 779 cases of Trichophyton tonsurans (32.6%), 738 cases of Trichophyton soudanense/T. violaceum (31%), and 445 cases of Microsporum audouinii (19.2%). Of note, T. tonsurans represents more than 80% of the cases in the French West Indies (Martinique and Guadeloupe). By contrast, zoophilic species were less prevalent with mainly M. canis (10.3%) confirming the shift from zoophilic to anthropophilic species observed in many centers during the last decades. During this survey, diagnosis methods were also collected. Most labs had a classical process for the diagnosis: microscopic direct examination associated to cultures on Sabouraud and Sabouraud-cycloheximide media (incubated between 25 ± 5°C for at least 3 weeks) in all laboratories. Identification of the causal dermatophyte was performed by microscopic and macroscopic examination of the cultures in 100% of the labs, with various specific culture media available when fructification was insufficient (mainly malt or potato-dextrose agar, or Borelli medium). New techniques were also implemented with the introduction of MALDI-TOF mass spectrometry identification in more than two third of the labs, and molecular identification available if necessary in half of the labs.

A total of 4395 tinea capitis cases were recorded within 36 French mycology laboratories during a 6-year period. An anthropophilic origin was predominant with 33%, 31%, and 18.8% of cases due to Trichophyton tonsurans, T. soudanense/T. violaceum, and Microsporum audouinii, respectively.

Detection of terbinafine-resistant Trichophyton indotineae isolates within the Trichophyton mentagrophytes species complex isolated from patients in Hue City, Vietnam: A comprehensive analysis.

The Trichophyton mentagrophytes complex comprises a group of dermatophyte fungi responsible for various dermatological infections. The increasing drug resistance of this species complex, especially terbinafine resistance of Trichophyton indotineae, is a major concern in dermatologist practice. This study provides a comprehensive analysis of T. mentagrophytes complex strains isolated from patients in Hue City, Vietnam, focusing on their phenotypic and genetic characteristics, antifungal susceptibility profiles, and molecular epidemiology. Keratinophilic fungi from dermatophytosis culture samples were identified morphologically and phenotypically, with species and genotypes confirmed by internal transcribed spacer sequencing and phylogenetic analysis. Antifungal susceptibility testing was carried out to evaluate their susceptibility to itraconazole, voriconazole, and terbinafine. The 24% (n = 27/114) of superficial mycoses were phenotypically attributed to T. mentagrophytes complex isolates. Trichophyton interdigitale, mainly genotype II*, was predominant (44.4%), followed by T. mentagrophytes genotype III* (22.2%), T. indotineae (14.8%), T. tonsurans (11.2%), and T. mentagrophytes (7.4%). While all isolates were susceptible to itraconazole and voriconazole, half of T. indotineae isolates exhibited resistance to terbinafine, linked to the Phe397Leu mutation in the SQLE protein. This study highlighted the presence of terbinafine-resistant T. indotineae isolates in Vietnam, emphasizing the need to investigate dermatophyte drug resistance and implement effective measures in clinical practice.

Species diversity within the Trichophyton mentagrophytes complex isolated from dermatophytosis in Hue City, Vietnam, was observed. Terbinafine-resistant T. indotineae isolates were detected for the first time in Vietnam, emphasizing the importance of implementing antifungal susceptibility testing to effectively manage and prevent the spread of resistant isolates.

Clinico-mycological and therapeutic updates on cutaneous dermatophytic infections in the era of Trichophyton indotineae.

Trichophyton indotineae has emerged as a novel dermatophyte species resulting in treatment recalcitrant skin infections. While the earliest reports came from India, T. indotineae has now spread to many parts of the world and is rapidly becoming a global health concern. Accurate identification of T. indotineae requires elaborate mycological investigations which is beyond the domain of routine microbiology testing. Extensive, non-inflammatory and atypical presentations are commonly seen with this novel species. T. indotineae shows an alarmingly high rate of mutations in the squalene epoxidase gene leading to lowered in vitro susceptibility to terbinafine. This has also translated into a lowered clinical response and requirement of a higher dose and much longer durations of treatment with the drug. Although the species remains largely susceptible to itraconazole, prolonged treatment durations are required to achieve cure with itraconazole. Fluconazole and griseofulvin do not have satisfactory in vitro or clinical activity. Apart from requirement of prolonged treatment durations, relapse postsuccessful treatment is a distressing and yet unexplained consequence of this "species-shift." Use of third generation azoles and combinations of systemic antifungals is unwarranted as both have not demonstrated clear superiority over itraconazole given alone, and the former is an important class of drugs for invasive mycoses.

Chrysosporium articulatum mimicking Trichophyton spp. infection in a cat: a case presentation and literature review.

BACKGROUND: Dermatophytosis is a common skin infection of cats and many other animals. A reliable diagnosis is crucial because of the zoonotic potential of dermatophytes. The routine mycological diagnostic procedures for dermatophytosis are widely known, but in the case of some isolates, identification based on phenotypic characteristics may be incorrect. Infections caused by Chrysosporium spp. are usually described in reptiles, but in other animals they are uncommon. CASE PRESENTATION: This study presents a description of a cat with dermatological lesions, that was mistakenly diagnosed with Trichophyton spp. dermatophytosis. Clinical material for mycological examination was collected from alopecic areas on the back of the neck, the ventral abdomen, and the hindlimbs. The initial identification based on phenotypic properties indicated Trichophyton spp. The result of the MALDI-ToF MS allowed the exclusion of the Trichophyton genus. Ultimately, the correct identification as Chrysosporium articulatum was obtained based on the sequencing of ribosomal genes. CONCLUSIONS: Interpretation of the results of the mycological examination of samples collected from animals' skin or hair shafts is always challenging. Thus, careful consideration of the primary cause of the clinical lesions observed on the skin is mandatory, and the culture results are worth supporting by molecular methods.

Molecular Detection of Dermatophytes and Nondermatophytes in Onychomycosis in Antalya, Turkey.

BACKGROUND: Onychomycosis is a chronic nail infection, and dermatophytes, yeasts, and nondermatophytic molds may be the causative agents. This study aimed to determine the etiological agents of onychomycosis by using conventional and molecular methods. METHODS: Between June 2020 and July 2021, 37 patients with a presumptive diagnosis of onychomycosis and mycological evidence (culture and/or EUROArray Dermatomycosis assay) were included in the study. Organisms detected in cultured nail specimens were identified by combined phenotypic characteristics and by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). An EUROarray Dermatomycosis assay was used for molecular detection of fungal pathogens. RESULTS: The EUROArray Dermatomycosis assay was positive for a single fungal target in 23 samples, and 14 samples were positive by culture. The most common pathogen was Trichophyton rubrum in both methods. Coinfection was detected in 14 samples by using molecular methods, and Trichophyton rubrum and Fusarium solani (9 samples) were the most common pathogens detected together. Trichophyton spp., nondermatophyte molds, and Candida spp. were detected in 33 (89.2%), 16 (43.2%), and 6 (16.2%) samples, respectively, when the two methods were evaluated together. CONCLUSIONS: Our results revealed that fungal culture allows the diagnosis of onychomycosis, but it is not as sensitive as the EUROArray Dermatomycosis test, especially in patients receiving antifungal therapy.

Onychoscopic characteristics of Trichophyton rubrum and Trichophyton interdigitalis fungal infections: A multicentric study.

BACKGROUND: Trichophyton rubrum and Trichophyton mentagrophytes variant interdigitalis are the most frequent etiologic agents of onychomycosis. Diagnosis of certainty requires mycological examination, which often results unfeasible. OBJECTIVES: The aim of our study is to describe pathogen specific dermoscopic features, allowing a differential diagnosis without the need for cultural examination, in order to prescribe the most appropriate treatment anyway. PATIENTS AND METHODS: We conducted an observational retrospective study on 54 patients with a culture proven diagnosis of distal subungual onychomycosis of the toenail, caused by Trichophyton rubrum or Trichophyton mentagrophytes variant interdigitalis. Using a videodermatoscope we collected data on nail colour (white, yellow, orange, brown, dark) and on dermoscopic patterns (aurora, spikes, jagged, ruin, linear edge, dots, striae). RESULTS: Fifty-four patients, with a total of 72 nails, were eligible for this study. Analysing the association between discoloration of the nail plate and type of infection (T. rubrum or T. interdigitalis), no correlation turned out to be statistically significant. Instead, significant associations between spikes and T. rubrum infection and striae and infection from T. interdigitalis were identified. Finally, a 100% specificity was identified for white colour and ruin pattern for T. rubrum infection, and brown colour, jagged border and aurora pattern for T. interdigitalis. CONCLUSIONS: Trying to find relationships between specific pathogens and dermoscopic patterns, we found out an association between spikes and striae and T. rubrum and T. interdigitalis respectively. Further larger studies are however necessary to evaluate our preliminary findings.

Treatment of onychomycosis in an era of antifungal resistance: Role for antifungal stewardship and topical antifungal agents.

A growing body of literature has marked the emergence and spread of antifungal resistance among species of Trichophyton, the most prevalent cause of toenail and fingernail onychomycosis in the United States and Europe. We review published data on rates of oral antifungal resistance among Trichophyton species; causes of antifungal resistance and methods to counteract it; and in vitro data on the role of topical antifungals in the treatment of onychomycosis. Antifungal resistance among species of Trichophyton against terbinafine and itraconazole-the two most common oral treatments for onychomycosis and other superficial fungal infections caused by dermatophytes-has been detected around the globe. Fungal adaptations, patient characteristics (e.g., immunocompromised status; drug-drug interactions), and empirical diagnostic and treatment patterns may contribute to reduced antifungal efficacy and the development of antifungal resistance. Antifungal stewardship efforts aim to ensure proper antifungal use to limit antifungal resistance and improve clinical outcomes. In the treatment of onychomycosis, critical aspects of antifungal stewardship include proper identification of the fungal infection prior to initiation of treatment and improvements in physician and patient education. Topical ciclopirox, efinaconazole and tavaborole, delivered either alone or in combination with oral antifungals, have demonstrated efficacy in vitro against susceptible and/or resistant isolates of Trichophyton species, with low potential for development of antifungal resistance. Additional real-world long-term data are needed to monitor global rates of antifungal resistance and assess the efficacy of oral and topical antifungals, alone or in combination, in counteracting antifungal resistance in the treatment of onychomycosis.

Antifungal activity of aminopyrrolnitrin against Trichophyton verrucosum in a guinea pig model of dermatophytosis.

BACKGROUND: Dermatophytosis is a common and major public health concern worldwide. Despite the increasing availability of antifungal drugs, relapses and untreated cases of dermatophyte infections are reported. Therefore, novel antifungal agents are required. Aminopyrrolnitrin (APRN) shows promise for dermatophytosis treatment because of its antifungal activity. OBJECTIVES: This study aimed to assess the antifungal properties of APRN against Trichophyton verrucosum (T. verrucosum), in both laboratory settings and a guinea pig model. METHODS: The minimum inhibitory concentrations (MICs) of APRN and enilconazole against T. verrucosum were determined according to the CLSI M38 method. The skins of 16 male guinea pigs were infected with 1.0 × 108 conidia of T. verrucosum and the animals were grouped into sets of four: negative control group (NC) received normal saline; positive control group (PC) received 2 µg/mL of enilconazole; and APRN4 and APRN8 received 4 and 8 µg/mL of APRN, respectively. Clinical, mycological and histological efficacies were measured after 10 days. RESULTS: The MIC90 of APRN and enilconazole against T. verrucosum was 4 and 2 µg/mL, respectively. The clinical scores of PC, APRN4, and APRN8 were significantly lower than those of NC. Clinical and mycological efficacies were higher for APRN8, APRN4 and PC. No fungi were observed in the skin tissues of APRN4 and APRN8, while fungi were observed in 50% of the PC. CONCLUSION: APRN showed antifungal activity against T. verrucosum in vitro and in vivo and is a potential candidate for the treatment of dermatophytosis.

Prolonged treatment of dermatophytosis caused by Trichophyton indotinea with terbinafine or itraconazole impacts better outcomes irrespective of mutation in the squalene epoxidase gene.

BACKGROUND: Over the past decades, the increasing incidence of recurrent dermatophytosis associated with terbinafine-resistant Trichophyton has posed a serious challenge in management of dermatophytosis. Independent reports of failure of treatment and high minimum inhibitory concentrations (MIC) of antifungals are available, but data correlating MIC and clinical outcomes is still sparse. Therefore, the present study was conducted to evaluate the outcomes of systemic treatment of dermatophytosis and its correlation with MIC of the etiological agents isolated from such patients. METHODS: Retrospective analysis of 587 consecutive patients with dermatophytosis was done from March 2017 to March 2019. Demographic and clinical details of the patients were noted, along with the results of direct microscopy and fungal culture. The isolates were identified by sequencing the internal transcribed spacer region of rDNA. Antifungal susceptibility testing was performed following the CLSI M38 protocol. Mutation in the squalene epoxidase (SE) gene was detected by DNA sequencing and ARMS-PCR. Based on the culture-positivity and prescribed systemic antifungal, patients were categorised into Group I culture-positive cases treated with systemic terbinafine and Group II culture-positive cases treated with systemic itraconazole, each for a total period of 12 weeks. RESULTS: In the present study, 477 (81.39%) were culture-positive; however, 12 weeks follow-up was available for 294 patients (Group I-157 and Group II-137) who were included for statistical analysis. In both groups [Group I-37/63 (51.4%) and Group II-14/54 (58.3%)], a better cure rate was observed if the initiation of therapy was performed within <6 months of illness. Treatment outcome revealed that if therapy was extended for 8-12 weeks, the odds of cure rate are significantly better (p < .001) with either itraconazole (Odd Ratio-15.5) or terbinafine (Odd Ratio-4.34). Higher MICs for terbinafine were noted in 41 cases (cured-18 and uncured-23) in Group I and 39 cases (cured-16 and uncured-23) in Group II. From cured (Group I-17/18; 94.4% and Group II-14/16; 87.5%) and uncured (Group I-20/23; 86.9% and Group II-21/23; 91.3%) cases had F397L mutation in the SE gene. No significant difference in cure rate was observed in patients with Trichophyton spp. having terbinafine MIC ≥ 1or <1 µg/mL (Group I-p = .712 and Group II-p = .69). CONCLUSION: This study revealed that prolonging terbinafine or itraconazole therapy for beyond 8 weeks rather than the standard 4 weeks significantly increases the cure rate. Moreover, no correlation has been observed between antifungal susceptibility and clinical outcomes. The MIC remains the primary parameter for defining antifungal activity and predicting the potency of antifungal agents against specific fungi. However, predicting therapeutic success based solely on the MIC of a fungal strain is not always reliable, as studies have shown a poor correlation between in vitro data and in vivo outcomes. To address this issue, further correlation of antifungal susceptibility testing (AFST) data with clinical outcomes and therapeutic drug monitoring is needed. It also highlights that initiation of the treatment within <6 months of illness increases cure rates and reduces recurrence. Extensive research is warranted to establish a better treatment regime for dermatophytosis.

Identification of primary metabolites in fungal species of Trichophyton mentagrophyte and Trichophyton rubrum by NMR spectroscopy.

BACKGROUND: Superficial mycoses are fungal infections limited to the outermost layers of the skin and its appendages. The chief causative agents of these mycoses are dermatophytes and yeasts. The diagnosis of dermatophytosis can be made by direct mycological examination with potassium hydroxide (10%-30%) of biological material obtained from patients with suspected mycosis, providing results more rapid than fungal cultures, which may take days or weeks. This information, together with clinical history and laboratory diagnosis, ensures that the appropriate treatment is initiated promptly. However, false negative results are obtained in 5%-15%, by conventional methods of diagnosis of dermatophytosis. OBJECTIVES: To study the metabolic profiles of the commonly occurring dermatophytes by NMR spectroscopy. PATIENTS/MATERIALS: We have used 1D and 2D Nuclear Magnetic Resonance (NMR) experiments along with Human Metabolome Database (HMDB) and Chenomx database search for identification of primary metabolites in the methanol extract of two fungal species: Trichophyton mentagrophyte (T. mentagrophyte) and Trichophyton rubrum (T. rubrum). Both standard strains and representative number of clinical isolates of these two species were investigated. Further, metabolic profiles obtained were analysed using multivariate analysis. RESULTS: We have identified 23 metabolites in the T. mentagrophyte and another 23 metabolites in T. rubrum. Many important metabolites like trehalose, proline, mannitol, acetate, GABA and several other amino acids were detected, which provide the necessary components for fungal growth and metabolism. Altered metabolites were defined between Trichophyton mentagrophyte and T. rubrum strains. CONCLUSION: We have detected many metabolites in the two fungal species T. mentagrophyte and T. rubrum by using NMR spectroscopy. NMR spectroscopy provides a holistic snapshot of the metabolome of an organism. Key metabolic differences were identified between the two fungal strains. We need to perform more studies on metabolite profiling of the samples from these species for their rapid diagnosis and prompt treatment.

Chinese expert consensus on management of antifungal-resistant dermatophytoses (2024 edition).

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal⁃Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.

Prior selection of itraconazole in the treatment of recalcitrant Trichophyton indotineae infection: Real-world results from retrospective analysis.

BACKGROUND: The number of terbinafine-resistant Trichophyton indotineae is increasing in recent years while the treatment is still a matter to discuss. OBJECTIVES: To explore the best therapeutic approach, we present real-world treatment of T. indotineae infection by analysing publicly available data. METHODS: We have reviewed all published articles, mainly including case reports and case series, on the drug-resistant T. mentagrophytes complex by using the key search terms to search the databases. RESULTS: We enrolled 25 articles from 14 countries, including 203 times of treatment information for 113 patients. The cure rate of itraconazole 200 mg per day at the fourth, eighth and the twelfth week were 27.27%, 48.48% and 54.55%, respectively, which was significantly higher than terbinafine 250 mg per day (8.77%, 24.56% and 28.07%) and even 500 mg/d terbinafine. Griseofulvin 500-1000 mg for 2-6 months may be effective while fluconazole had no record of successful treatment. Voriconazole and ravuconazole had potential therapeutic efficacy. Topical therapy alone showed limited therapeutic efficacy, but the combination with oral antifungals can be alternative. CONCLUSION: Oral itraconazole 200 mg per day for 4-8 weeks was the most effective treatment out of these commonly used antifungal drugs, and can be prior selection.

Dermatophytes and skin dermatophytoses in Southeast Asia-First epidemiological survey from Cambodia.

BACKGROUND: Dermatomycoses count to the most frequent dermatoses in Cambodia. OBJECTIVES: The aim of this survey was to investigate the occurrence of dermatophytes in this Southeast Asian country. METHODS: From June 2017 to July 2018, skin scrapings were taken from 67 patients with superficial dermatophytosis for mycological diagnostics. Identification of dermatophytes was confirmed by sequencing of the 'internal transcribed spacer'-(ITS) region of the rDNA, and the gene of the Translation Elongation Factor (TEF)-1α. RESULTS: Patients were suffering from tinea corporis and tinea inguinalis/cruris 42/67 (63%), tinea capitis/faciei 14/67 (21%), tinea corporis/capitis/faciei 6/67 (9%), tinea manuum/pedis 2/67 (3%), tinea pedis 2/67 (3%) and tinea manuum 1/67 (1%). Both, by culture and/or PCR, a dermatophyte was detected in 52 (78%) out of 67 samples. Culture positive were 42 (81%) of 52, PCR positive were 50 (96%). The following dermatophytes were found: Trichophyton (T.) rubrum, 36/52 strains (69%, 29 by culture), T. mentagrophytes/T. interdigitale (TM/TI) 9/52 (17%, six by culture) and Microsporum (M.) canis 5/52 strains (10%, by culture). One strain of Nannizzia (N.) incurvata 1/52 (2%) and N. nana 1/52 (2%) was isolated. Based on sequencing, we demonstrated that two T. mentagrophytes strains out of the nine TM/TI represented the new ITS genotype XXV Cambodia. We found one T. mentagrophytes strain genotype VIII (now, reclassified as T. indotineae). This isolate was terbinafine resistant, and it exhibited the amino acid substitution Phe397Leu in the squalene epoxidase. Three strains of T. interdigitale genotype II* were isolated. CONCLUSION: This is the first survey on epidemiology of dermatophytes in Cambodia. Currently, T. rubrum represents the most frequent species in Cambodia. One Indian strain genotype VIII T. mentagrophytes was found. A highlight was the first description of the new T. mentagrophytes genotype XXV Cambodia.

Terbinafine resistance in Trichophyton mentagrophytes and Trichophyton rubrum in the Czech Republic: A prospective multicentric study.

BACKGROUND: Terbinafine, an allylamine antifungal, is crucial for treating dermatophytosis by inhibiting squalene epoxidase (SQLE) in the ergosterol biosynthetic pathway. However, resistance is emerging, particularly in India and Southeast Asia, but reports of resistance spread worldwide. Despite this, comprehensive studies on terbinafine resistance in Trichophyton are still limited. OBJECTIVES: This research aimed to determine the prevalence of terbinafine resistance in the Czech Republic, with a focus on Trichophyton rubrum and Trichophyton mentagrophytes, and investigate the underlying molecular mechanisms. PATIENTS/METHODS: A total of 514 clinical strains of T. rubrum and 240 T. mentagrophytes collected from four Czech clinical institutions were screened for terbinafine resistance. Molecular investigations included DNA sequencing, specifically the ITS rDNA region and SQLE gene, as well as antifungal susceptibility testing following EUCAST guidelines. RESULTS: While no resistance was observed in T. rubrum, 2.5% of T. mentagrophytes strains exhibited resistance, marked by the F397L mutation in SQLE. Notably, resistance surged from 1.2% in 2019 to 9.3% in 2020 but reverted to 0% in 2021. All resistant strains were identified as T. mentagrophytes var. indotineae. Resistant strains exhibited high MICs for terbinafine (≥4 mg L-1 ) but low MICs to the other seven antifungals tested except for fluconazole. CONCLUSIONS: This study highlights the emergence of terbinafine-resistant T. mentagrophytes strains in the Czech Republic, with the F397L mutation being pivotal. Due to the relatively low resistance level, the current guidelines for dermatomycosis treatment in the Czech Republic remain effective, but ongoing surveillance is essential for timely adaptations if resistance patterns change.

Potential emergence of terbinafine resistance by squalene epoxidase gene mutations: An 18-month cohort study of onychomycosis patients in the United States.

BACKGROUND: There is a concerning rise in antifungal-resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene. OBJECTIVES: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States. METHODS: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18-month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real-time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His). RESULTS: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution. CONCLUSION: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk.

Kerion Celsi in infants and children-A narrative review 2010-2023.

Kerion Celsi is an inflammatory, deep fungal infection of the scalp. It is rare in neonates but gets more common in children about 3 years and older. It represents with swelling, boggy lesions, pain, alopecia and purulent secretions. Secondary bacterial infection is not unusual after maceration. Extracutaneous manifestations include regional lymphadenopathy, fever and very rare fungemia. Id-reactions can occur. Diagnosis is based on clinical suspicion, clinical examination and medical history. Diagnosis should be confirmed by microscopy, fungal culture and molecular procedures. The most common isolated fungal species are anthropophilic Trichophyton (T.) tonsurans and zoophilic Microsporum (M.) canis, while geophilic species and moulds rarely cause Kerion Celsi. Treatment is medical with systemic and topical antifungals supplemented by systemic antibiotics when necessary, while surgery needs to be avoided. Early and sufficient treatment prevents scarring alopecia. The most important differential diagnosis is bacterial skin and soft tissue infections.