Search Results (348)

Deep dermatophytosis is a rare, life-threatening fungal infection characterised by the invasion of dermatophytes beyond the superficial layers of keratinised tissue into the dermis and subcutaneous tissues. The present review aimed to identify the current knowledge on the role of Caspase Recruitment Domain-containing protein 9 (CARD9) deficiency in the pathogenesis, clinical spectrum, diagnosis, and management of deep dermatophytosis. For innate immune activation, CARD9 acts as an adaptor molecule. Basically, CARD9 helps mediate the connection between the fungal pattern recognition receptor (Dectin-1) and the NF-κB and MAPK signalling pathways, and it mediates cytokine production, thereby activating phagocytic activities. Thereby, any change or mutation in the CARD9 gene may disrupt these pathways, leading to dysfunctional neutrophils and impaired Th17-mediated antifungal immunity. Clinically, patients with CARD9 deficiency are immunocompetent but susceptible to recurrent and/or severe fungal infections [Candida, dermatophytes (Trichophyton spp.), and phaeohyphomycetes]. Deep dermatophytosis in these patients is usually chronic, treatment-resistant, and characterized by erythematous papules, nodules, plaques, ulcers, or necrotic lesions, most of which occur on the lower limbs. It usually occurs in adulthood and is more common in males. There have been instances of geographic clustering of CARD9 deficiency in Asia, North Africa, and the Middle East. Early recognition and genetic diagnosis of CARD9 mutations in patients with recurrent or atypical deep dermatophytosis. Although antifungal therapy is essential, hematopoietic stem cell transplantation can be a definitive treatment for selected patients with CARD9 deficiency. Thus, CARD9 deficiency is a critical factor in the better management of patients but remains an underrecognized cause of severe, treatment-resistant deep dermatophytosis, and early genetic diagnosis is essential for guiding targeted management and improving patient outcomes. This review emphasises the importance of CARD9 in antifungal immunity and underscores the need for greater clinical awareness and the incorporation of genetic evaluation into the management of deep dermatophytosis. Full article

This study evaluates the antifungal activity of Lippia gracilis Schauer essential oil traditionally used in northeastern Brazil for the treatment of skin disorders. The essential oil isolated from fresh leaves collected in Ceará, Brazil, was chemically characterized by GC–MS, showing a thymol-dominant profile (37.52%), accompanied by p-cymene (12.13%), γ-terpinene (9.29%), and gurjunene (10.95%). Antifungal assays revealed significant activity against several dermatophyte species with MIC and MFC values ranging from 50 to 100 μg/mL. Biofilm assays against Epidermophyton floccosum demonstrated strong inhibitory effects by disrupting biofilm formation, altering fungal morphology, and promoting in vitro skin cells migration, while also showing effective preventive effects in an ex vitro nail infection model. These findings support the potential of L. gracilis essential oil as a multifunctional natural antifungal agent for the management of refractory dermatophytosis and onychomycosis, and provide scientific validation for its traditional use in skin infection treatment. Full article

Background/Objectives: Onychomycosis is a fungal nail infection that may present with severe, atypical, or treatment-resistant features in people living with HIV. Despite its clinical importance, evidence regarding its epidemiology, causative agents, and relationship with immune status remains limited. This systematic review aimed to evaluate the association between onychomycosis and HIV, focusing on prevalence, clinical characteristics, etiologic agents, and CD4+ T lymphocyte counts at diagnosis. Methods: A systematic review was conducted following PRISMA guidelines. MEDLINE/PubMed, SciELO, Scopus, and Scilit were searched for studies published between October 2015 and July 2025 in English and Spanish. Eligible studies included case reports, case series, and observational studies involving people with HIV and confirmed onychomycosis. Data extraction was performed independently, and findings were analyzed descriptively. Results: Thirty studies comprising 1296 patients were included; 306 had detailed clinical descriptions. Most cases were reported in the Americas (85.8%) and predominantly involved male patients. CD4+ counts were available in 123 individuals; 52% had <200 cells/µL, including 18 with <50 cells/µL. Trichophyton rubrum was the most frequently identified etiologic agent. Conclusions: Onychomycosis in HIV shows etiologic diversity and commonly affects patients with advanced immunosuppression, though it may also occur with partial immune preservation. Prospective standardized studies are needed. Full article

Dracocephalum botryoides Stev. (Lamiaceae) is an endemic species of the Caucasus region with a history of traditional medicinal use, although the biological properties of its essential oil remain insufficiently characterized. In this study, the essential oil obtained from the aerial parts of D. botryoides collected in northern Azerbaijan was evaluated for its chemical composition, antioxidant, antimicrobial, antibiofilm, and cytotoxic activities. GC–MS analysis revealed a terpene-rich profile, with p-cymene (15.2%), T-cadinol (6.2%), caryophyllene oxide (6.0%), β-caryophyllene (5.8%), and sabinene (5.1%) as the major constituents. The essential oil showed notable antioxidant activity in DPPH and ABTS radical scavenging assays, with IC₅₀ values of approximately 60 and 63 µg/mL, respectively. The essential oil exhibited antimicrobial activity, with minimum inhibitory concentration (MIC) values of 0.2% (v/v) against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, and Candida albicans ATCC 10231. Higher MIC values were recorded for Escherichia coli ATCC 25922 and Candida glabrata ATCC 2001 (1.0% v/v), while the highest MIC value was observed for Trichophyton rubrum ATCC 28188 (2.5% v/v). The essential oil also inhibited biofilm formation, and scanning electron microscopy supported these findings by demonstrating reduced biofilm coverage and disrupted biofilm architecture. In vitro assays using HaCaT human keratinocytes indicated low cytotoxicity of the essential oil at concentrations below 100 µg/mL. These results suggest that the terpene-rich essential oil of D. botryoides possesses noteworthy antioxidant, antimicrobial, and antibiofilm potential. Full article

Trichophyton indotineae is an emerging dermatophyte associated with extensive, chronic, recalcitrant, and frequently terbinafine-resistant dermatophytosis worldwide. In this study, 30 T. indotineae strains isolated in Italy were investigated. The isolates were obtained from patients originating from Asian countries, from patients from other countries, and from Italian patients who reported no travel outside Italy in the preceding years. Clinical isolates were identified by internal transcribed spacer (ITS) sequencing and analyzed to assess the occurrence and molecular basis of terbinafine resistance. Terbinafine resistance was detected in 18 strains (60%) using a real-time PCR assay. Sequencing of the squalene epoxidase (SQLE) gene revealed mutations associated with resistance, including L393S in nine strains and F397L in another nine strains. NGS analysis confirmed two terbinafine-resistant strains carrying the L393S and F397L mutations, respectively, and detected the A448T mutation in one terbinafine-susceptible strain. These findings demonstrate the presence of terbinafine-resistant T. indotineae across five regions of Italy and confirm the occurrence of SQLE mutations previously linked to antifungal resistance. Data obtained also support a link with endemic Asian areas, other than suggesting the possible occurrence of autochthonous transmission in Italy. Full article

The emergence of antimicrobial resistance and the increasing incidence of cancer have highlighted the urgent need to develop new drugs; therefore, the discovery of new bioactive molecules is an important goal for future research. In this study, freshwater fungi isolated from submerged Phragmites australis from Egypt were screened for antimicrobial and cytotoxic activities. Using ITS1 and ITS4 primers, eight frequently occurring Sordariomycetes taxa were identified and were then selected for further evaluation of bioactivity. Ethyl acetate crude extracts (A–H) were evaluated for antimicrobial activity using the agar disk-diffusion method. Extracts A and E, derived from Chaetomium globosum SCUF0000404 (PX596738) and Chaetomium madrasense SCUF0000401 (PX596735), respectively, showed broad-spectrum activity at 100 mg/mL against bacterial pathogens, including Staphylococcus aureus ATCC 29213 (15.33 and 18.00 mm), Streptococcus pyogenes ATCC 19615 (11.00 mm), Escherichia coli ATCC 35218 (10.33 and 10.67 mm), Klebsiella pneumoniae ATCC 700603 (14.00 and 16.67 mm), and Pseudomonas aeruginosa ATCC 27853 (13.33 and 16.33 mm), and show antifungal activity against Candida albicans ATCC 14053 (20.33 mm), Candida krusei ATCC 6258 (15.67 and 15.33 mm), Trichosporon asahii AMS 187 (17.00 and 17.67 mm), Exserohilum rostratum AMS 1077 (34.00 and 33.67 mm), and Trichophyton indotineae AMS 180 (38.33 and 34.00 mm). Selective cytotoxic effects on the breast cancer cell line MDA-MB-231 were observed by extracts A and E at IC₅₀ = 309 and 277 μg/mL, while non-selective cytotoxic effects on the normal HUVEC cell line were found with IC₅₀ = 919 and 796 μg/mL, respectively. Characterization of the most effective extracts A and E by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) shows that they have a wide range of secondary metabolites, including cytochalasans, azaphilone alkaloids, steroids, terpenoids, flavonoids, and phenols. These findings underscore the chemical diversity and therapeutic potential of freshwater fungi from Egypt. Full article

Tinea incognito is an atypical form of dermatophytosis caused by previous use of topical or systemic immunosuppressive therapy, most often corticosteroids. Modification of the clinical presentation frequently leads to diagnostic delay and misdiagnosis, especially in patients with concomitant chronic inflammatory skin diseases such as psoriasis. We present a narrative review of the literature on tinea incognito in patients with psoriasis during immunosuppressive therapy. We screened 386 abstracts and included 16 comparable case reports focusing on tinea incognito occurring in patients with psoriasis or during antipsoriatic treatment. The review summarizes clinical presentations, diagnostic challenges, and therapeutic approaches reported in the literature. Additionally, we present a clinical case of a 27-year-old man with a long history of plaque psoriasis treated with methotrexate and cyclosporine. The patient developed rapidly progressive skin lesions with pustular features and further deterioration despite systemic antipsoriatic therapy. Initial mycological examinations were negative. Histopathological examination revealed a chronic purulent perifollicular inflammatory process with extension into the subcutaneous tissue. The correct diagnosis was confirmed after a repeat skin biopsy with periodic acid–Schiff and Grocott staining and fungal culture of the skin tissue, which revealed Trichophyton rubrum. The review highlights that clinical features are often nonspecific and may overlap with inflammatory dermatoses. This underscores the need for a high index of clinical suspicion for fungal infection in atypical or refractory psoriatic lesions. It also emphasizes the importance of repeated mycological and histopathological examinations to achieve an accurate diagnosis, avoid inappropriate escalation of immunosuppression, and enable timely antifungal treatment. Full article

Dermatophytosis is a superficial fungal skin disease of cats and dogs. The most common pathogens of small animals belong to the genera Microsporum and Trichophyton. It is an important skin disease because it is contagious and can be transmitted to people. Refractory dermatophytosis has become a disease of increasing concern in dermatological practice due to poor responses to standard antifungal therapy. The condition is characterised by chronicity, recurrence, or persistence despite adequate treatment. This report describes the clinical presentation and therapeutic management of refractory dermatophytosis in an 8-year-old intact male Spitz dog weighing 10 kg presenting with persistent alopecia, scaling, erythema, and pruritus despite multiple courses of systemic antifungal agents (itraconazole) and topical antifungal agents (2% miconazole shampoos and terbinafine-containing dusting powder). Diagnosis was confirmed by microscopic examination, culture, and punch biopsy. Due to the lack of response to standard therapy, posaconazole was initiated based on antifungal susceptibility testing (AFST). Marked clinical improvement was observed without adverse effects. This report documents a case of refractory dermatophytosis in which AFST informed the selection of posaconazole therapy. It highlights the diagnostic challenges of recurrent dermatophytosis, suggests that AFST-guided treatment strategies may help manage infections unresponsive to standard antifungal therapy, and demonstrates that posaconazole is a promising alternative antifungal agent for refractory dermatophytosis in dogs. Full article

The aim of this paper is to evaluate the performance of the Derma-SR-screen agar for accurate discrimination between susceptible and non-susceptible clinical Trichophyton isolates. Consecutive Trichophyton isolates, received for identification and susceptibility testing, were screened for terbinafine and itraconazole resistance using Liofilchem Derma-SR-screen 4-well panels alongside EUCAST reference testing (E.Def 11.0). EUCAST tentative ECOFFs (terbinafine: T. rubrum 0.03 mg/L; T. indotineae 0.125 mg/L; itraconazole: both species: 0.25 mg/L) were applied for wild-type/non-wild-type classification. Plates were evaluated after 5 days of incubation at 25 °C, with growth graded 0-+++. Faint growth (+) was disregarded. All isolates underwent sqle sequencing. Forty isolates were included; 25 were non-wild-type harbouring Sqle alterations (F397I (number (n) = 1), F397L (n = 17), L393F (n = 3), L393S (n = 1), and Q408L (n = 3)). On day 5, 21 isolates reached +++ growth in the control well; a further 10 reached this level on day 6. The remaining isolates reached a ++/+++ score after 5/6 days (n = 7/n = 2). The 0.125 mg/L terbinafine agar correctly identified 7/8 non-wild-type T. indotineae isolates (4/5 F397L and 3/3 Q408L alterations), all 17 non-wild-type and eight wild-type T. rubrum isolates, as well as the five wild-type isolates of other Trichophyton spp. The 0.016 mg/L agar correctly identified all 17 non-wild-type T. rubrum isolates, but misclassified 2/8 wild-type isolates as non-wild-type. All isolates were wild-type to itraconazole and correctly identified. The Derma-SR-screen agar resulted in correct classification of 24/25 (96%) sqle mutant T. indotineae and T. rubrum isolates. Two wild-type T. rubrum isolates grew at the 0.016 mg/L terbinafine agar suggesting possible reduced agar potency at this concentration. Full article

Rapid responses to environmental changes are essential for maintaining fitness. In pathogenic fungi such as the dermatophyte Trichophyton interdigitale, appropriate responses to environmental shifts determine successful infection. Transcriptional regulation and alternative splicing (AS) are key modulators of fungal adaptation and pathogenesis. Here, we validated the role of the transcription factor PacC in coordinating AS in T. interdigitale grown in infection-mimicking medium. RNA-seq analysis of a ΔpacC mutant revealed a predominance of intron retention events, mainly involving introns 1 and 2, indicating defective splicing and potential nonsense-mediated decay of genes related to ion transport, metabolism, and genome maintenance. These alterations compromised energy balance, ergosterol biosynthesis, and cellular homeostasis. PacC-dependent AS generated alternative isoforms of cytoskeletal and metabolic proteins, including myosin-1 and a GH3 β-glucosidase, potentially modulating enzymatic activity, metabolic burden, and cell wall remodeling during infection. Exon-skipping in the chromatin remodeler RSC1 suggests PacC involvement in epigenetic regulation under host-mimicking conditions. Transmission electron microscopy revealed possible Woronin bodies, cytoplasmic disruption, and cell wall thinning in the mutant. Overall, PacC integrates transcriptional and post-transcriptional regulation to promote adaptation, survival, and virulence, highlighting AS as a regulatory layer linking environmental sensing to metabolic and epigenetic plasticity in pathogenic fungi. Full article

Background/Objectives: This article describes the results of an analysis of the sensitivity of dermatophytosis pathogens to terbinafine, conducted by the authors based on a review of available scientific publications and data from their own research. Currently, no information is available on the sensitivity of Kazakh isolates obtained from patients at dermatological clinics. The aim of this study was to compile data on the resistance of dermatophytes to terbinafine over the past decade worldwide and investigate the sensitivity of dermatophyte isolates collected from patients in Astana, Kazakhstan, to terbinafine. Methods: A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, utilizing the Pubmed and Cochrane Library databases with specific keywords. The sensitivity of the dermatophytes to terbinafine was assessed using EUCAST E.Def 11.0 method. Results: Screening of terbinafine susceptibility among Kazakh clinical isolates revealed that all Microsporum canis strains (57/57, 100%) were sensitive to the drug. Among 33 Trichophyton spp. isolates, 4 (12.1%) demonstrated resistance to terbinafine, with MIC values ranging from 0.125 to 1.5 µg/mL. The resistant isolates belonged to the species T. indotineae, T. interdigitale, and T. mentagrophytes. Conclusions: Terbinafine remains highly effective against Microsporum canis in Kazakhstan, while a small proportion of Trichophyton isolates show resistance. Continuous monitoring of dermatophyte susceptibility is warranted to guide effective treatment. Full article

Stilbenoids are plant-derived chemical compounds that are classified as phytoalexins; recent focus has been drawn, especially on astringin, piceid, piceatannol, pterostilbene, pinosylvin, and resveratrol. These substances have been extensively studied for a variety of beneficial properties, including their effects on pathogenic microorganisms, parasites, and viruses. In their antifungal capacity, they are effective against Aspergillus spp., Botrytis spp., Candida spp., Trichophyton spp., and other fungi; tested stilbenoids have exhibited fungicidal and fungistatic effects, and inhibition of biofilm formation. Against parasites, they are effective against Echinococcus spp., Leishmania spp., Schistosoma spp., Trypanosoma spp., Toxoplasma spp., among others. Relevant action mechanisms include a reduction in parasitic enzymatic activity and inhibition of proliferation. They are also effective against different DNA and RNA viruses; the relevant mechanisms comprise reduction in viral replication, inhibition of viral genome expression, and viral attachment to cells. The toxicity of stilbenoids has been reviewed in recent papers, and, in most cases, the effective concentrations applied are well below the toxicity limit. Full article

Dermatomycoses pose significant zoonotic and public health challenges, involving interactions among fungal agents, host immunity, and environmental reservoirs. Eight cases of dermatophyte infection involving five humans, two cats and one dog were investigated in the Umbria region applying a One-Health approach, as recommended by the CDC. Fungal isolates were identified by mycological and molecular methods as Microsporum canis (n = 4), Nannizzia gypsea (n = 3), and Trichophyton mentagrophytes var. mentagrophytes genotype III* (n = 1). The source of infection was identified in four cases enabling the implementation of appropriate treatment, removal of fomites, and environmental sanitization; as a result, no recurrences were observed. In the remaining cases, environmental assessments showed no fungal burden, indicating likely incidental transmission. Close cohabitation or contact with cats emerged as a risk factor. The patient’s medical history should always include exposure to animals in order to facilitate early recognition, correct management, and prevention. Interdisciplinary collaboration among dermatologists, veterinarians, and laboratory technicians is essential to optimize therapeutic outcomes and to prevent potential antifungal resistance phenomena. Moreover, continuous surveillance under a One-Health framework will enable better epidemiological understanding of dermatophyte species dynamics, particularly zoonotic agents. Full article

Background/Objectives: Fingernail onychomycosis differs etiologically and epidemiologically from toenail infections and is frequently complicated by colonization and mixed growth. Reliable interpretation of microscopy–culture correlations is essential for avoiding overdiagnosis and guiding therapy. This study aimed to characterize the diagnostic structure, species distribution, and antifungal susceptibility patterns of fingernail onychomycosis in a large routine-laboratory cohort, and to evaluate the performance of a five-tier operational classification integrating microscopy and semi-quantitative culture. Methods: Laboratory records from 1075 patients with clinically suspected fingernail onychomycosis (including nail and periungual samples) were analyzed retrospectively (2017–2024). Direct microscopy with calcofluor white, semi-quantitative culture, and MALDI-TOF MS identification were performed. Cases were categorized based on predefined criteria combining microscopic elements with colony quantity and purity. Species distribution, age–sex patterns, diagnostic concordance between microscopy and culture, and results of EUCAST broth microdilution testing for selected yeasts were assessed. Results: The overall proportion of mycologically positive cases was similar in women and men, although age-dependent patterns differed. Microscopic findings correlated with culture outcomes, with hyphae predicting dermatophytes, yeast cells predicting ascomycetous yeasts, and negative slides aligning with the absence of growth. Yeasts predominated (Candida parapsilosis 30.9%, C. albicans 18.5%), dermatophytes were mainly Trichophyton rubrum, and molds were uncommon. Periungual swabs showed species distributions closely matching those from nail samples and demonstrated high analytical concordance. EUCAST MICs revealed species-dependent variation, including elevated amorolfine MICs in C. parapsilosis and reduced fluconazole activity in Wickerhamomyces pararugosa. Conclusions: Fingernail onychomycosis in this cohort was predominantly yeast-associated, with predictable microscopy–culture relationships and distinct age–sex patterns. The five-tier operational framework improved classification of infection versus colonization, and is proposed as a preliminary tool requiring clinical validation, while contemporary MIC data highlighted clinically relevant interspecies differences. The absence of clinical correlation data (symptoms, severity, treatment history) remains the primary limitation, preventing definitive distinction between infection and colonization in all cases. Full article

Background: Onychomycosis is a common nail infection primarily caused by Trichophyton rubrum, posing therapeutic challenges due to poor antifungal penetration and high recurrence rates. Conventional treatments include topical and systemic antifungals, but novel approaches such as laser therapy and chemical agents like nitric acid have emerged as promising alternatives or adjuncts. However, comparative evidence regarding the clinical and mycological efficacy of these treatments remains limited. Objectives: We aimed to assess and compare the clinical and mycological efficacy of three therapeutic modalities—69% nitric acid, 1064 nm Nd:YAG laser, and their combination—in the treatment of Trichophyton rubrum onychomycosis over a 12-month follow-up period. Methods: A prospective, comparative, observational study was conducted, assigning patients with confirmed onychomycosis to one of three treatment groups: nitric acid, Nd:YAG 1064 nm laser, or combination therapy. Clinical and mycological cure rates, mean time to clinical resolution, changes in Onychomycosis Severity Index [OSI] scores, and mycological relapse rates were assessed over a 12-month follow-up. Results: All three groups demonstrated significant improvement in both clinical and mycological cure rates, with the combination therapy yielding the most favorable outcomes in terms of response speed and durability. Laser and nitric acid monotherapies were also effective, though associated with lower cure rates and longer times to resolution. The relapse rate was lowest in the combination group. Conclusions: The combination of nitric acid and Nd:YAG laser appears to be a more effective therapeutic option for Trichophyton rubrum onychomycosis, offering superior clinical and mycological outcomes compared to monotherapies, with faster resolution and lower relapse rates. These findings suggest that combination therapy may optimize the management of this challenging nail infection. Full article