Search Results (344)

A commercially available nitric oxide (NO)-releasing solution (NORS) has demonstrated in vitro efficacy for dermatophytosis, but a NO-releasing gel (NORG) may be more suitable for patient self-application. We present a preliminary investigation of NORS for tinea pedis and an in vitro investigation of NORG for dermatophyte infection, to complement the existing published data and expand support for a possible role of NO formulations in superficial dermatophyte infection. In vitro usage of NORS and NORG is reviewed. The antifungal efficacy of NORG was assessed via time-kill assays, zone of inhibition tests with synthetic dermal membrane permeation, and scanning electron microscopy. A randomized, controlled pilot study of NORS for tinea pedis investigated the safety and efficacy of treatment over three consecutive days, with a day-31 follow-up. The NORG demonstrated rapid fungicidal activity against T. rubrum and T. mentagrophytes and effective dermal membrane penetration while retaining antifungal action. Significant morphological damage to fungal cells was noted, indicating possible fungicidal activity. The clinical NORS treatment reduced the clinical symptom severity score by 67% on average, with no significant safety findings. These findings, in addition to existing publications, support NO-releasing formulations as potential therapies that warrant further clinical investigation for superficial fungal infection. Full article

Superficial mycoses (dermatomycoses) are a growing healthcare concern due to antifungal resistance, particularly among aging and immunocompromised populations. Multiple efforts are underway to develop novel antifungals, including discovering new compounds with known or new mechanisms of action, extending indications or repurposing existing medications, and utilizing vaccination and nanotechnology platforms. Herein, we conducted a scoping review of novel antifungals for the treatment of dermatomycoses. An electronic literature search restricted to the past 10 years was performed in January 2026 using PubMed and Embase (Ovid). Olorofim and ME1111 represent novel drug classes that target intracellular metabolism. New agents belonging to the azole class demonstrate reduced drug–drug interactions (oteseconazole), a broader antifungal spectrum (voriconazole), and reduced pharmacokinetic complexity (fosravuconazole, super-bioavailable itraconazole). Other investigational compounds include allicin, a phytocompound, and miltefosine, a repurposed antileishmanial drug. Based on our current understanding of dermatophyte immunity, antimicrobial peptides and vaccines targeting virulence factors (e.g., subtilisins) represent novel strategies. Nanotechnology platforms also show promise in introducing new antifungal agents (e.g., metal nanoparticles, nitric oxide-releasing nanoparticles), as well as developing topical formulations to enhance the bioavailability and safety profiles of existing antifungals (amphotericin B, ketoconazole, voriconazole). 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

Dermatophytosis is a common zoonotic fungal infection in companion animals, most frequently caused by Microsporum canis, while the geophilic species Nannizzia gypsea may occasionally infect cats. Conventional morphological identification of dermatophytes is often challenging due to phenotypic similarities, underscoring the importance of molecular confirmation. In this study, dermatophyte field isolates obtained from cats with suspected dermatophytosis were identified using cultural characteristics and Internal Transcribed Spacer (ITS) region sequencing. Phylogenetic analysis based on ITS sequences showed that the isolates were highly similar to each other and clustered closely with reference strains and previously reported dermatophyte strains from different geographical regions. Subsequently, the in vitro antifungal activity of a propolis extract collected from the Muğla region (Türkiye) was evaluated using the agar dilution method at concentrations ranging from 6.25 to 100 mg/mL. At all tested concentrations, propolis inhibited mycelial growth in all four molecularly confirmed dermatophyte field isolates, whereas substantial growth was observed in the negative control plates. These findings indicate that Muğla propolis exhibits in vitro antifungal activity at the tested concentrations against dermatophyte field isolates and warrants further investigation as a potential natural antifungal source. Full article

Dermatophytes are fungi that infect the human skin and its appendages. With new pathogenic species emerging and resistance to first-line drugs rising, microbiologic diagnosis and species identification are becoming even more important. In this study, the DermaGenius^® 2.0/3.0 Complete multiplex real-time PCR and the EUROArray Dermatomycosis kits were compared to fungal culture and with each other; 78 reference strains and 124 clinical samples were analyzed. Both the DermaGenius^® kit (97%; 95%CI 89–100%) and the EUROArray assay (91%; 95% CI: 82–96%) were sensitive when analyzing on-panel reference strains. In clinical samples, the DermaGenius^® assay provided a positive result in 63 out of 124 (51%) samples and the EUROArray assay in 74 out of 124 (60%) samples. Both kits supported the diagnosis and species identification of culture-negative samples, and samples with growth of unconventional species. However, there was suspicion of false-positive results with F. solani in the EUROArray kit both in clinical and reference strains. The most common conventional dermatophytes in this study combining all methods were T. rubrum/soudanense (n = 40) and T. interdigitale/mentagrophytes (n = 11). In summary, both PCR kits were sensitive for the diagnosis and species identification of dermatophytoses. Combining culture and a PCR-based method can increase the diagnostic yield and compensate for the weakness of the other methods. The optimal PCR-based kit, and especially the optimal panel size, depends on the local epidemiology of dermatophytes. 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/Objectives: Tinea capitis is traditionally a childhood infection, yet recent reports describe its emergence among older adults. In this population, hormonal changes, comorbidities, and frequent corticosteroid use may modify clinical presentation and delay diagnosis. This systematic review aimed to consolidate current evidence on Tinea capitis in individuals aged 65 years or older, focusing on epidemiologic, clinical, and mycological characteristics as well as therapeutic outcomes. Methods: Following PRISMA 2020 guidelines, a comprehensive search was conducted in the PubMed, Scopus, and SciELO databases for studies published between 1978 and February 2025. Eligible articles included case reports, case series, and clinical studies involving patients ≥65 years with confirmed Tinea capitis. Two independent reviewers screened and extracted data on demographics, comorbidities, risk factors, clinical manifestations, diagnostic methods, etiologic agents, and treatment response. Results: Sixty-three studies comprising 91 patients from 19 countries were included. Most cases originated from Spain (n = 27) and the United States (n = 12). Females accounted for 90.1% of cases. The leading comorbidities were diabetes mellitus (37.5%) and hypertension (21.9%). Topical corticosteroid use (40.7%) and pet exposure (27.8%) were frequent risk factors. Misdiagnosis occurred in 37.4% of patients, commonly as seborrheic dermatitis or erosive pustular dermatosis. The inflammatory variant predominated (65.9%), with kerion reported in 42.9%. Microsporum canis was the predominant agent (26.9%, n = 24), while Trichophyton rubrum and Trichophyton tonsurans were equally frequent (both 19.1%, n = 17). Systemic antifungal therapy achieved clinical cure in 91.2% of cases. Conclusions: Tinea capitis in the elderly is an underrecognized and often misidentified scalp infection. Awareness of its variable presentation and systematic mycological assessment are crucial to ensure timely therapy and prevent scarring alopecia. Full article

Onychomycosis is a common nail disease that manifests with varying severity and frequency in specific patient populations, warranting a personalized treatment approach. Novel topical antifungals, such as efinaconazole 10% approved for use in North America and Japan, offer a safe treatment option for many of these patients, though real-world use requires special considerations. In this scoping review, a literature search was conducted in October 2025 using PubMed, Embase (Ovid), the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science (Core Collection). In children and adolescents (≥6 years), efinaconazole 10% has shown higher efficacy rates than in adults, possibly attributed to less nail trauma, thinner nail plates, and faster nail growth. In the elderly, a mycological response can precede visual nail improvements, which may require extending treatment beyond the standard 48-week regimen, along with intermittent maintenance therapies. Although antifungal resistance is a concern, dermatophytes—including terbinafine-resistant strains—have generally shown high susceptibility to efinaconazole. In diabetic individuals, onychomycosis should be treated promptly to prevent secondary complications. Efinaconazole 10% showed similar efficacy in this population, regardless of glycemic control. In historically underserved populations, efinaconazole 10% showed no significant difference in efficacy for Latino/Hispanic patients, though further research is needed. Overall, efinaconazole 10% solution was well-tolerated across patient groups, with application-site reactions occurring without systemic sequalae. Healthcare providers are advised to check for concomitant tinea pedis, which increases the risk of relapse or re-infection, and advise patients on nail polish use, which may degrade after topical antifungal application. A shared decision-making framework can help improve treatment compliance and patient satisfaction. Full article

Tinea is a superficial fungal infection of keratinized structures caused by specific filamentous fungi called dermatophytes. Terbinafine, a drug used to treat tinea, is poorly soluble in water, and its delivery into the skin via nanoparticle formulation usingpoly(lactic-co-glycolic acid) (PLGA) has been demonstrated. In this study, we investigated the preparation conditions for nanoparticles (NPs) to achieve efficient intradermal delivery of terbinafine. Terbinafine-loaded PLGA NPs were prepared using the nanoprecipitation method, and the particle size distribution and average particle size were measured using dynamic light scattering. Skin permeability tests were conducted using mouse dorsal skin, and the amount of terbinafine delivered into the skin was measured to evaluate the release behavior in the skin. In the preparation of terbinafine-loaded PLGA NPs, under conditions where the external solution was purified water, the mean volume diameter was 40.49 ± 15.63 nm, the terbinafine-loaded content was 3.31 ± 0.29%, and the entrapment efficiency was 55.08 ± 4.88%. Under conditions of an external solution containing 1.0 × 10⁻³ w/v% arginine(Arg) aq. solution, the mean volume diameter was 41.71 ± 16.08 nm, the terbinafine-loaded content was 5.17 ± 0.37%, and the entrapment efficiency was 86.48 ± 6.01%. The entrapment efficiency and content were higher under the condition using 1.0 × 10⁻³ w/v% Arg aq. solution compared to purified water. In addition, in the skin permeability test, no drug was detected in the receptor solution sampled from both the NPs suspension group and the simple solution group, and no drug was detected in the intradermal solution in the simple solution group. The intradermal drug concentration was 77.94 ± 10.66 µg/g under conditions where purified water was used as the dialysate, and 96.42 ± 61.62 µg/g under conditions using 1.0 × 10⁻³ w/v% arginine, exceeding the reported minimum inhibitory concentration (MIC) of 8.87 µg/g, suggesting the efficacy of terbinafine-loaded PLGA NPs for the treatment of tinea versicolor. Since tinea treatment is a long-term process, it is desirable to deliver a stable amount of drug to the treatment site at all times. Therefore, the nanoparticle preparation conditions using purified water as the external solution, where the intradermal drug concentration exceeded the MIC and remained stable in the skin permeability test, were suggested to be suitable for tinea treatment. Full article

Dermatophytes can cause infections of the skin, hair and nails. This study aims to investigate the thiosemicarbazides with nitroimidazole moiety against Trichophyton spp. The activity of fourteen thiosemicarbazide derivatives was evaluated against Trichophyton spp. The minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) showing 50% and 90% reduction in fungal growth after 4–7 days of incubation (MFC₅₀ and MFC₉₀) were used. The 6 and 11 (MICs ≤ 125 µg/mL), followed by the 3, 5 and 7 containing a fluorophenyl group (MIC = 125 µg/mL, MFC = 125–250 µg/mL) exhibited the best activity and specifically T. mentagrophytes, respectively. Fluorine-containing derivatives (5–9) demonstrated 2–4-fold higher activity (MIC = 31.25–1000 µg/mL) against T. rubrum than T. mentagrophytes, than their chlorinated counterparts (2–4) with MIC = 62.5–500 µg/mL. The position of the fluorine atom within the phenyl ring was important, as observed for derivatives with fluorine in the meta position (3, 6), while the para position was associated with enhanced selectivity. A methoxy group in the meta position of the phenyl ring exhibited the strongest, broadest-spectrum activity. Notably, the introduction of the trifluoromethylphenyl moiety (pharmacophore) led to the disappearance of antifungal properties. Full article

Sertaconazole nitrate (SN), a broad-spectrum antifungal agent, is clinically employed against diverse dermatophyte infections. Its therapeutic efficacy, however, is constrained by poor aqueous solubility (0.006 mg/mL) and insufficient skin penetration from current commercial formulations. To address these limitations, this research focused on developing, optimizing (using a 3² factorial design), and assessing a topical nanovesicular gel incorporating sertaconazole nitrate-loaded ultraflexible liposomes (SN-UFLs) to enhance antifungal performance. The vesicles exhibited near-spherical morphology, with sizes ranging from 104.40 ± 1.20 to 151.90 ± 2.14 nm, zeta potential (ZP) values between −21.50 ± 1.25 and −51.20 ± 2.25 mV, and entrapment efficiency (EE) values from 77.60 ± 2.50% to 86.04 ± 3.20%. The optimized SN-UFL formulation (OPT-SN-UFL) was then integrated into a carbopol gel base. This SN-UFL-Gel was characterized for pH (6.5 ± 0.20), viscosity (499.66 ± 15 cP), spreadability (205 ± 1.50%), extrudability (154.18 ± 2.48 g/cm²), and drug content (96.7 ± 2.50%), as well as ex vivo skin permeation, skin irritation potential, and in vitro and in vivo antifungal efficacy. Compared with the marketed formulation, higher drug permeation and skin deposition were observed for SN-UFL-Gel. The SN-UFL-Gel exhibited a larger zone of inhibition (25 ± 1.50 mm) against Candida albicans compared to the commercially available formulation (20 ± 1.72 mm). The in vivo animal studies showed that SN-UFL-Gel showed better antifungal activity by efficient inhibition of infection induced in rats with Trichophyton mentagrophytes. The SN-UFL-Gel showed no signs of skin irritation and was stable at 4 ± 1, 25 ± 2, and 40 ± 2 °C for 3 months. Conclusively, the current work divulged successful augmentation of the overall effectiveness of sertaconazole nitrate by using deformable liposomes as a promising nanocarrier. Full article

Onychomycosis is a therapeutically challenging fungal infection. Systemic antifungals are limited by adverse effects and drug interactions, while topical therapies may fail to achieve therapeutic nail bed concentrations. Nitric oxide (NO), a small, diffusible free radical with broad-spectrum antimicrobial activity, offers a novel approach to overcoming these barriers. We assessed the penetration and subsequent efficacy of a nitric oxide–releasing gel (NORG) in the treatment of onychomycosis. Ex vivo human nail models assessed NORG’s transungual penetration and antifungal activity via colorimetric, immunohistochemical, and microbiological assays. NORG eradicated Trichophyton mentagrophytes completely (0 CFU/g), outperforming terbinafine (3.58 ± 0.2 log₁₀ CFU/g). In an ex vivo infection model, NORG achieved fungal clearance within 14 days, continuing to Day 30 treatment end, with no regrowth during 21 days of incubation post-treatment. Clinical data from patients with onychomycosis who received topical NORG therapy show that NORG penetrated the nail plate and nail bed, as evidenced by s-nitrosothiol accumulation and progressive discoloration. The NORG formulation demonstrates in vitro efficacy; controlled trials are warranted to fully assess clinical efficacy and safety of this NORG formulation in humans, and establish optimal treatment protocols. Full article

Superficial fungal skin infections are common but often misdiagnosed, which may result in inappropriate treatment and the worsening of symptoms. An accurate and timely diagnosis is essential to differentiate these infections from similar conditions such as secondary syphilis, annular psoriasis, and pityriasis rosea. This single-centre prospective cohort study at the National Skin Centre, Singapore, evaluated the diagnostic agreement between direct microscopy and fungal culture. Between August and December 2022, 268 skin scrape samples were collected from 149 patients with suspected fungal infections. Microscopy identified 67 (25.0%) positives, while fungal culture detected 42 (16.7%) positives. Among the 252 samples tested with both methods, 213 (84.5%) showed concordant results (κ = 0.487, p < 0.0001), a finding that indicates moderate agreement. The most commonly cultured organisms were Trichophyton rubrum and T. mentagrophytes. Our findings suggest that both microscopy and fungal culture may be performed to prevent true-positive cases from being missed. However, in cases where cost is a concern, microscopy can be selected as an initial diagnostic tool. Should microscopy be negative in cases with high clinical suspicion for fungal infection or when empirical treatment fails, culture remains a valuable follow-up test. These findings support a stepwise diagnostic approach—using microscopy first, then followed by culture when necessary—to improve diagnostic accuracy while enabling timely treatment. Full article