Search Results (23)

The expansion of urbanized areas is leading to increased human−animal interactions, thereby creating potential new ecosystems for wildlife. In this context, dermatophytoses are of particular significance. This investigation aimed to evaluate the presence of dermatophyte species in wild animals enrolled by passive control and targeted active control plans or deceased for causes independent of this study and analyzed for necroscopic procedures. From 2010 to 2024, a total of 704 samples were collected and analyzed by conventional and molecular assays. Dermatophytes were detected in 77 animals. The molecular approach identified Paraphyton mirabile (5.96%), Trichophyton mentagrophytes complex (2.41%), Microsporum canis (0.71%), Arthroderma curreyi, A. thuringense (0.57% each), A. uncinatum, and A. eboreum (0.43% each). In one animal a co-infection of T. mentagrophytes and M. canis was found. Considering wild animals as sentinels for dermatophytoses, it is crucial to implement surveillance to prevent potential zoonotic outbreaks. Full article

Trichophyton indotineae is an emerging dermatophyte species responsible for recalcitrant and terbinafine-resistant dermatophytosis, raising concerns over diagnostic accuracy and treatment efficacy. This study aimed to improve the identification and resistance profiling of T. indotineae by integrating molecular methods with machine learning-assisted analysis of MALDI-TOF mass spectra. A total of 56 clinical isolates within the Trichophyton mentagrophytes complex were analyzed using ITS and ERG1 gene sequencing, antifungal susceptibility testing, and MALDI-TOF MS profiling. Terbinafine resistance was detected in 23 isolates and correlated with specific ERG1 mutations, including F397L, L393S, F415C, and A448T. While conventional MALDI-TOF MS failed to reliably distinguish T. indotineae from closely related species, unsupervised statistical methods (PCA and hierarchical clustering) revealed distinct spectral groupings. Supervised machine learning algorithms, particularly PLS-DA and SVM, achieved 100% balanced accuracy in species classification using 10-fold cross-validation. Biomarker analysis identified discriminatory spectral peaks for both T. indotineae and T. mentagrophytes (3417.29 m/z and 3423.53 m/z). These results demonstrate that combining MALDI-TOF MS with multivariate analysis and machine learning improves diagnostic resolution and may offer a practical alternative to sequencing in resource-limited settings. This approach could enhance the routine detection of terbinafine-resistant T. indotineae and support more targeted antifungal therapy. Full article

Dermatophytes are keratinophilic fungi that cause a wide range of superficial infections in humans and animals. The Trichophyton mentagrophytes species complex is one of the most clinically important groups due to its broad host range, widespread distribution, and increasing involvement in antifungal-resistant infections. Here, we described the epidemiology of T. mentagrophytes over a period of 4 years detected in the northeastern part of Italy and provided the genomic characterization of clinical isolates. ITS sequence analysis revealed that among the 13 strains studied, 11 belonged to the T. mentagrophytes complex. In detail, nine were classified as genotype I/II and two as genotype VII. Analysis of the SQLE gene revealed that nine strains harbored a wild-type gene, while two carried a Lys276Asn mutation. Genomic analysis was performed on three clinical T. mentagrophytes strains that belonged to genotype I/II, revealing the presence of different virulence factors including MEP-1, MEP-2, MEP-3, and MEP-5. Phylogenetic analysis based on core-genome SNPs demonstrated that the two genomes included in this study were clonally related to a T. mentagrophytes strain isolated in China in 2024. In conclusion, our study highlights the importance of genomic characterization in order to trace the epidemiology of dermatophytes worldwide and to characterize emerging strains. Full article

Background/Objectives: Terbinafine has been the gold standard for the management of superficial fungal infections. The etiological agent generally is Trichophyton rubrum (T. rubrum); however, there has been increased reporting of a new terbinafine-resistant strain of the T. mentagrophytes complex (T. mentagrophytes ITS genotype VIII otherwise known as T. indotineae). Here, we review the epidemiology, clinical features, diagnosis, and treatment of T. rubrum and T. indotineae infections. Methods: We conducted a systematic literature search using PubMed, Embase (Ovid), and Web of Science, resulting in 83 qualified studies with data summarized for clinical features, antifungal susceptibility, and terbinafine resistance mechanisms and mutations. Results: Dermatophytosis is most commonly caused by T. rubrum; however, in certain parts of the world, especially in the Indian subcontinent, T. indotineae infections have been reported more frequently. The majority of T. rubrum isolates remain susceptible to terbinafine (over 60% of isolates show MIC₅₀ and MIC₉₀ < 0.5 µg/mL). In contrast, for T. indotineae, 30% of isolates exhibit MIC₅₀ ≥ 0.5 µg/mL and 80% exhibit MIC₉₀ ≥ 0.5 µg/mL. Frequently detected squalene epoxidase (SQLE) mutations in T. rubrum are Phe397Leu/Ile (41.6%) and Leu393Phe (20.8%); in T. indotineae, these include Phe397Leu (33.0%) and Ala448Thr (24.5%). Other potential terbinafine resistance mechanisms in T. rubrum and T. indotineae are discussed. Conclusions: T. rubrum generally remain susceptible in vitro to terbinafine in contrast to T. indotineae. The essential components of an effective antifungal stewardship emphasize accurate clinical and laboratory diagnosis, susceptibility testing, and appropriate antifungal therapy selection with a multidisciplinary approach. Full article

The identification of filamentous fungi by matrix-assisted laser desorption/ionization–time of flight mass spectrometry (MALDI–TOF MS) represents a challenge due to their complex taxonomy and the lack of comprehensive databases. The aim of this study was to evaluate the current status of available MALDI–TOF MS databases for the identification of dermatophytes, including commercial, in-house, and web-based databases. We collected 289 dermatophyte strains from different centers and analyzed them using four databases and a combination of them. The combination of commercial and in-house databases was shown to improve the identification rate and accuracy at the species level. For Trichophyton rubrum, the concordance among all databases was above 90.0%. For the T. mentagrophytes group, correct identification at the species level ranged from 30.0 to 78.9%, depending on the database, and showed very low agreement among them. The addition of the novel species T. japonicum to our in-house database resulted in the successful identification of this species. On the other hand, T. interdigitale and T. tonsurans were the species most frequently misidentified by MALDI–TOF MS. Through deep spectra analysis of both species, up to 29 protein peaks were found to be suitable for their differentiation, demonstrating the potential of peak analysis in differentiating closely related species. In conclusion, improvements of the databases with new strains resulted in increased identification accuracy at the species level. This, combined with peak analysis, could improve the overall identification of dermatophytes by MALDI–TOF MS in clinical laboratories. Full article

Dermatophytes are commonly encountered pathogens in clinical practice causing superficial infections of the skin, hair, and nails. These pathogens are often found on animals such as livestock (e.g., cattle, rabbits) and pets (e.g., cats, hedgehogs) that can lead to spillover infections in human populations. Here, we reviewed published reports (2009–2024) of dermatophyte infections in animals and in humans with a history of animal contact. A literature search was completed in October 2024 using PubMed, Embase (Ovid), and Web of Science (Core Collection), which identified 250 articles. Generally, dermatophytes tend to infect younger animals with long hair and exhibit a species-specific host range. Microsporum canis was the most commonly reported species—linked to cats—that can cause tinea capitis, especially concerning the development of kerion in children. Trichophyton verrucosum is strongly associated with cattle. The Trichophyton mentagrophytes complex shows a diverse range of animal hosts, with rabbits being most frequently reported; however, T. mentagrophytes var. erinacei is almost exclusively isolated from hedgehogs, and T. mentagrophytes var. benhamiae is more commonly found on rodents (e.g., guinea pigs). Lastly, the geophilic Nannizia gypsea has been isolated from both dogs and cats. Managing dermatophyte zoonoses is an ongoing challenge, as healthcare providers may empirically treat with corticosteroids or antibacterial agents due to its atypical inflammatory appearance. Evidence of in vitro resistance against griseofulvin and fluconazole has been documented in multiple zoonotic dermatophyte species. Resistance development against terbinafine and itraconazole is also a possibility, although the number of reports is scarce. Under the principles of the One Health approach, research on human fungal diseases should take animal and environmental factors into account. A renewed call for increased testing efforts is warranted. Full article

Up to one-quarter of the United States population is affected by tinea pedis (athlete’s foot). Tinea pedis of the web space (interdigital tinea pedis) is a common clinical presentation causing skin macerations and fissures. A “dermatophytosis complex” (i.e., concomitant bacterial colonization) further complicates treatment. Here, we examined records of 14,429 skin specimens taken from the feet of dermatology and podiatry outpatients over a 4.6-year period; all specimens were subjected to multiplex qPCR diagnosis for the detection of dermatophytes, Candida, Corynebacterium minutissimum, Pseudomonas and Staphylococcus aureus. A literature search was conducted to review the reported prevalence of fungal and bacterial agents. In both interdigital and plantar foot specimens, dermatophytes (33.3–33.8%) and S. aureus (24.3–25%) were found to be the predominate pathogens. In the interdigital space, a higher prevalence of C. minutissimum (15.7% vs. 7.9%) and Pseudomonas (23.5% vs. 9.6%) was found. The detection of Pseudomonas was more likely to be observed in the presence of Candida, reflecting a higher risk of mixed infection. In dermatophyte-positive specimens, the “dermatophytosis complex” variant was observed at 45.5% (SD: 2.3). An analysis of patient characteristics showed male patients exhibiting higher likelihoods for dermatophyte, C. minutissimum, Pseudomonas and S. aureus detections. The elderly were disproportionately infected with Candida. In children, an S. aureus detection was more common, which could be attributed to impetigo. The recent literature lacks reporting on concomitant bacterial colonization in tinea pedis patients, likely due to the reliance on fungal culture supplemented with antibiotics. Geographical variation has been identified in the detection of the Trichophyton mentagrophytes complex. In conclusion, PCR diagnosis serves as a valuable tool for the management of tinea pedis. An accurate and timely detection of fungal pathogens and concomitant bacterial colonization can better inform healthcare providers of appropriate treatment selection. Full article

Trichophyton (T.) mentagrophytes ITS genotype VIII, also known as Trichophyton indotineae, is a new species of the T. mentagrophytes/T. interdigitale complex and its first records, albeit under a different species name, are from the Indian subcontinent, Middle Eastern Asia, and West Asia. T. mentagrophytes genotype VIII (T. indotineae) has spread globally and has now been documented in over 30 countries. The aim of this study was to investigate the occurrence and proportion of terbinafine- and itraconazole-resistant isolates of T. mentagrophytes ITS genotype VIII (T. indotineae) in Bangladesh. This was part of an official collaborative project between IADVL (Indian Association of Dermatologists, Venereologists, and Leprologists) and Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh. Over a period of 6 months, ninety-nine patients of chronic recalcitrant tinea corporis were recruited from BSMMU hospital. Species identification was performed by fungal culture and morphological observation of the upper and lower surfaces of fungal colonies, as well as by using fluorescent microscopy. In addition, a PCR (polymerase chain reaction)-ELISA was performed to group the patients into those with the T. mentagrophytes/T. interdigitale complex. The internal transcribed spacer (ITS) gene was sequenced. Samples were tested for resistance to terbinafine and itraconazole by mutational analyses of the squalene epoxidase (SQLE) and the ergosterol 11B (ERG11B) genes. A total of 79/99 samples showed a positive culture. In 76 of these isolates, T. mentagrophytes ITS genotype VIII (T. indotineae) could be reliably identified both by culture and molecular testing. Resistance testing revealed terbinafine resistance in 49 and itraconazole resistance in 21 patients. Among these, 11 patients were resistant to both the antifungal agents. Mutations L393S, L393F, F397L, and F397I of the SQLE gene were associated with terbinafine resistance. Resistance to itraconazole could not be explained by mutations in the ERG11B gene. Infections with T. mentagrophytes ITS genotype VIII (T. indotineae) have become a public health issue with potentially global ramifications. About 62% of samples from Bangladesh showed resistance to terbinafine, making oral itraconazole the most effective drug currently available, although resistance to itraconazole and both terbinafine and itraconazole also exists. Full article

Onychomycosis is a common fungal infection that affects the nails and accounts for approximately 50% of all nail diseases. The main pathogens involved include dermatophytes, such as Trichophyton rubrum, members of the T. mentagrophytes complex, and emerging pathogens in this infection, T. schoenleinii and T. tonsurans. Tea tree (Melaleuca alternifolia Cheel) essential oil (EO) has been proposed as a promising natural alternative to traditional treatments due to its antimicrobial properties. Among its more than 100 compounds, terpinen-4-ol is one of the main contributors to the antifungal action of this EO. To determine the antifungal activity of tea tree EO against dermatophytes, we designed an in vitro study using EUCAST-AFST protocols to obtain the values of MIC (minimum inhibitory concentration) and MFC (minimum fungicidal concentration) of several commercial M. alternifolia Cheel EOs against three species of dermatophytes isolated from clinical samples with suspected toenail onychomycosis. The results showed that the microorganism most sensitive to the action of the EO was T. rubrum, which had an MIC value more than 13 times lower than the value obtained for T. schoenleinii (0.4% v/v), the most resistant isolate. No differences in antifungal activity were observed by the analysed EOs or between the MIC and MFC values. These in vitro results suggest that tea tree EO is a viable option for the alternative treatment of onychomycosis, although clinical studies are needed to confirm the long-term antifungal activity, safety and efficacy of the oils studied in a clinical context. Full article

Background: In recent decades, globalization and international migration have increased the spread of infectious agents, including dermatophytes. Although considered minor infections, dermatophytoses are highly contagious, and they significantly reduce the quality of life, inducing itching, burning, sleep disturbances, and even depressive states. Moreover, the increasing resistance to antifungals threats the public health and burdens the costs for the healthcare system. Methods: DermaGenius^® Resistance Multiplex real-time PCR assay allowed to analyze the terbinafine susceptibility/resistance of 172 Trichophyton strains, which were isolated from human and animal samples collected from 2016 to May 2024 and previously identified by Sanger sequencing. Results: All the 11 animal strains belonged to the T. interdigitale/T. mentagrophytes complex and tested terbinafine sensitive. Out of 161 human strains, 9 (5.6%) showed terbinafine resistance and 7 (4.3%) were identified as T. indotineae. Conclusions: This study provides preliminary data about behavior toward antifungals in animals and finalizes the scientific information currently available about human strains, highlighting the importance of the One Health concept. Moreover, it supports the relevant role of T. indotineae as an emerging dermatophyte with high proportion of terbinafine resistance. Full article

Introduction: Efinaconazole 10% topical solution labeling for onychomycosis describes phase III trials of 12 months of treatment; the slow growth of onychomycotic nails suggests a longer treatment period may increase efficacy. We present here the first evaluation of extended use of efinaconazole 10% topical solution for up to 24 months. Materials and Methods: Enrolled patients (n = 101) had one target great toenail with mild to moderate distal lateral subungual onychomycosis and applied efinaconazole 10% topical solution to all affected toenails once daily for 18 months (EFN18) or 24 months (EFN24). Efficacy and safety were evaluated at each visit by visual review and mycology sampling. Results: Regarding the target toenail for patients treated for 24 months (EFN24), mycological cure (negative microscopy and culture) was 66.0% at Month 12, increasing to 71.7% at Month 24; effective cure (mycological cure and ≤10% affected nail) was 13.2% at Month 12, rising to 22.6% at Month 24. Mild to moderate application site reactions (symptoms of erythema/scaling) were the only efinaconazole-related reactions, in eight patients (7.9%). No systemic efinaconazole events or drug interactions were found. Patients aged 70 years or more had similar efficacy to younger patients at all time periods and did not show any increased treatment risks. Thinner nails exhibited better clearance versus thicker nails. A higher proportion of patients with Trichophyton mentagrophytes complex infection experienced application site reactions (35.7%), and a higher effective cure was found at Month 24 versus T. rubrum patients. Conclusion: There is a trend of increasing mycological cure and effective cure beyond Month 12 to Month 24, without an increased safety risk. The enrolled population in this trial was significantly older than in the phase III trials, with a greater degree of onychomycosis severity; however, increased age did not appear to reduce the chance of efficacy to Month 24 in this study. Our data suggest that lack of ability to clear nail dystrophy remains a significant problem for patients, rather than any lack of efinaconazole action over long-term treatment periods. Full article

Background: Dermatophytosis is a prevalent superficial infection caused by filamentous fungi, primarily affecting the skin and/or its appendages. In recent years, there has been a notable increase in mycotic strains resistant to standard antifungal therapies, including Trichophyton indotineae, a dermatophyte of the Trichophyton mentagrophytes complex. This review aims to provide a comprehensive overview of the treatment options for T. indotineae, elucidating their effectiveness in managing this challenging mycotic infection. Methods: For this review, a search was conducted in the PubMed, Scopus, Web of Science, Embase, and Google Scholar databases, encompassing all published data until March 2024. English-language articles detailing therapy outcomes for patients confirmed to be affected by T. indotineae, identified through molecular analysis, were included. Results: Itraconazole was shown to be a good therapeutic choice, particularly when administered at a dosage of 200 mg/day for 1–12 weeks. Voriconazole was also demonstrated to be effective, while terbinafine exhibited a reduced response rate. Griseofulvin and fluconazole, on the other hand, were found to be ineffective. Although topical treatments were mostly ineffective when used alone, they showed promising results when used in combination with systemic therapy. Mutational status was associated with different profiles of treatment response, suggesting the need for a more tailored approach. Conclusions: When managing T. indotineae infections, it is necessary to optimize therapy to mitigate resistances and relapse. Combining in vitro antifungal susceptibility testing with mutational analysis could be a promising strategy in refining treatment selection. Full article

Trichophyton indotineae is an emerging dermatophyte species that plays a relevant role in human healthcare. It has been associated with severe chronic skin infections and a high level of terbinafine resistance. T. indotineae is endemic to India, Iran, and Iraq but several cases have been reported in Europe, recently. In this manuscript, the authors report the first clinical description of a tinea corporis and onychomycosis due to T. indotineae. The patient was a 42-year-old female from India that has lived in Umbria (Central Italy) for the last two years. Firstly, a dermatological examination suggested dermatophytosis: mycology isolation from cultures and macro- and microscopical features identified the colonies as belonging to the T. mentagrophytes/T. interdigitale species complex. Subsequently, ITS1/ITS4 end-point PCR and Sanger sequencing identified the strain as T. indotineae. Lastly, a DermaGenius^® Resistance Multiplex real-time PCR assay was carried out, targeting the mutations in the SQLE gene to establish terbinafine resistance or susceptibility of the strain. The melting curve observed was compatible with wild-type positive control, identifying the strain as T. indotineae terbinafine-sensitive. An oral terbinafine treatment was associated with a topical ciclopirox nail solution, resulting in remission in its clinical manifestation. On 3 July 2023, the local Prevention Service notified the case to the Ministry of Health that then reported the information at national and international levels. Full article

Otomycosis (OM) is a superficial fungal infection of the external auditory canal (EAC) with a worldwide prevalence ranging from 9% to 30%. Commonly, otomycoses are caused by Aspergillus (A.) niger complex and Candida spp. Other causative agents are yeasts of the genera Cryptococcus spp., Rhodotorula spp., Geotrichum candidum, dermatophytes (Trichophyton mentagrophytes), and non-dermatophytes molds (Fusarium spp., Penicillium spp., Mucorales fungi). The widest range of different species causing OM are found in the territories of Iran, India, China, Egypt, Mexico, and Brazil. Fungal infection of the EAC varies from mild to severe forms. It can be acute, subacute, or chronic, and is often unilateral, while the bilateral form is more common in immunocompromised patients. From an epidemiological point of view, tropical and subtropical climates are the most significant risk factor for the development of otomycosis. Other predisposing conditions include clothing habits, EAC hygiene practices, long-term antibiotic therapy, diabetes, and immunodeficiency. Since it is often difficult to distinguish otomycosis from an infection of a different origin, laboratory-based evidence, including standard procedures (microscopy and cultivation), is essential for diagnosis. For the treatment of this superficial fungal infection, there are no official therapeutic guidelines and protocols. However, many antifungals for local application, such as polyene, imidazoles, and allylamines, can be applied, as well as systemic antimycotics (triazoles) in severe forms of infection. Full article

Taxonomic delineation of etiologic agents responsible for recalcitrant dermatophytosis causing an epidemic in India is still debated. The organism responsible for this epidemic is designated as T. indotineae, a clonal offshoot of T. mentagrophytes. To evaluate the real identity of the agent causing this epidemic, we performed a multigene sequence analysis of Trichophyton species isolated from human and animal origin. We included Trichophyton species isolated from 213 human and six animal hosts. Internal transcribed spacer (ITS) (n = 219), translational elongation factors (TEF 1-α) (n = 40), ß-tubulin (BT) (n = 40), large ribosomal subunit (LSU) (n = 34), calmodulin (CAL) (n = 29), high mobility group (HMG) transcription factor gene (n = 17) and α-box gene (n = 17) were sequenced. Our sequences were compared with Trichophyton mentagrophytes species complex sequences in the NCBI database. Except for one isolate (ITS genotype III) from animal origin, all the tested genes grouped our isolates and belonged to the “Indian ITS genotype”, currently labeled as T. indotineae. ITS and TEF 1-α were more congruent compared to other genes. In this study, for the first time, we isolated the T mentagrophytes ITS Type VIII from animal origin, suggesting the role of zoonotic transmission in the ongoing epidemic. Isolation of T. mentagrophytes type III only from animal indicates its niche among animals. Outdated/inaccurate naming for these dermatophytes in the public database has created confusion in using appropriate species designation. Full article