Search Results (27)

Onychomycosis, a fungal nail infection, affects about 4% of the global population. Current topical antifungals like ciclopirox and amorolfine have limited effectiveness, highlighting the need for better treatments. WSNS-PO is a novel water-soluble therapy designed to treat and prevent onychomycosis by enhancing nail health. This study evaluated WSNS-PO’s ability to penetrate the nail plate and to treat and prevent infection by Trichophyton rubrum using bovine hoof membranes and human nail clippings. The anti-fungal efficacy of WSNS-PO was additionally evaluated against other dermatophytes, non-dermatophyte fungi, and yeast. The results showed that WSNS-PO effectively permeated nails and reduced and prevented the colonization of human nail fragments by T. rubrum ex vivo, demonstrating an efficacy comparable to ciclopirox and amorolfine. WSNS-PO also prevented the transfer of T. rubrum infection between nails and inhibited the fungal colonization of human skin by dermatophyte and non-dermatophyte fungi and yeast. Together, these results indicate that WSNS-PO possesses fungistatic, barrier-forming, and anti-adhesive properties, suggesting that it holds promise as an onychomycosis treatment against dermatophytes, yeast, and molds. Full article

Dermatomycosis, including the most prevalent onychomycosis, significantly impacts patients’ quality of life due to its chronic nature and high recurrence rate. Conventional diagnostic methods are often limited by low sensitivity and specificity and prolonged turnaround times. This study evaluates the EUROArray Dermatomycosis Platform, a microarray-based molecular assay, for its performance in identifying fungi causing dermatomycosis. Forty reference fungal strains, covering on-panel and off-panel species, and 120 clinical samples from patients with suspected dermatomycosis were analyzed. The platform’s accuracy was compared to microscopy and/or culture as the diagnostic standard. The assay demonstrated 100% analytical sensitivity and 97.1% analytical specificity, correctly identifying 33 of 34 fungal species while misclassifying one. In clinical samples, the assay showed good sensitivity (78.6%) and high specificity (91.7%), detecting additional positive cases missed by culture, which highlights the assay’s ability to identify non-viable fungi and low fungal loads. The assay achieved a positive predictive value of 75.9% and a negative predictive value of 92.8%, reinforcing its diagnostic reliability. Despite some discordances, the assay provides rapid results and broad-spectrum fungal detection, positioning it as a valuable complement to conventional diagnostics. Future improvements, including expanding the identification panel and optimizing sample handling, could further enhance its clinical utility. Full article

Background: Onychomycosis is the most prevalent nail disease, posing a challenge for health professionals in terms of treatment. Conventional topical antifungal treatments can often prove insufficient, and the use of oral antifungal drugs carries a high frequency of adverse events and drug–drug interactions. Objective: The primary aim of this study was to determine the cure rate of onychomycosis using a combined treatment of diode laser and photodynamic therapy with red-laser photodynamic therapy (PDT) and toluidine blue gel. Methods: A series of onychomycosis cases were treated and monitored for 6 months with eight applications of diode laser therapy. This treatment was combined with three applications of red-laser PDT paired with toluidine blue gel. Clinical cure was evaluated one week after the treatment’s conclusion, while mycological cure was assessed via microbiological culture. Results: The study included 12 patients and a total of 17 nails. At the end of treatment, clinical, mycological, and complete cure rates were 100% for all patients and nails. No adverse reactions were reported during or after the PDT application. However, all patients experienced pain during laser application, and two patients experienced hematoma and subungual blistering post-treatment. Two patients (2/12) experienced recurrence in three nails (3/17; recurrence rate: 17.6%) within 6 months following treatment. Conclusions: The combination of diode laser therapy and red-laser PDT with toluidine blue gel seems effective and safe for the treatment of mild, moderate, and severe onychomycosis. Full article

Onychomycosis is a common fungal nail infection for which new antifungals are needed to overcome antimicrobial resistance and the limitations of conventional treatments. This study reports the development of antifungal nail lacquers containing oregano essential oil (OEO), rosemary essential oil (REO), and biogenic silver nanoparticles (bioAgNPs). The formulations (F) were tested against dermatophytes using agar diffusion, ex vivo nail infection, and scanning electron microscopy techniques. They were evaluated for their pharmacotechnical characteristics and by FTIR-PAS to assess permeation across the nail. F-OEO and F-OEO/bioAgNPs were promising candidates for the final nail lacquer formulation, as they permeated through the nail and showed antifungal efficacy against dermatophytes-contaminated nails after 5 days of treatment. Treated nails exhibited decreased hyphae and spores compared to the untreated control; the hyphae were atypically flattened, indicating loss of cytoplasmic content due to damage to the cytoplasmic membrane. The formulations were stable after centrifugation and thermal stress, maintaining organoleptic and physicochemical characteristics. Both F-OEO and F-OEO/bioAgNPs had pH compatible with the nail and drying times (59–90 s) within the reference for nail lacquer. For the first time, OEO and bioAgNPs were incorporated into nail lacquer, resulting in a natural and nanotechnological product for onychomycosis that could combat microbial resistance. Full article

Diabetes Mellitus (DM) is a significant global concern. Many diabetic patients will experience complications due to angiopathy, neuropathy, and immune dysfunction, namely diabetic foot ulcers (DFU) and diabetic foot infections (DFI), which can result in lower limb amputation and potentially death. The prevalence of common superficial fungal infections, such as tinea pedis and onychomycosis, can directly increase a diabetic patient’s risk of developing both DFU and DFI. In this review article, we discuss the etiology of diabetic foot complications as well as considerations for both screening and management. We also discuss the role of the dermatologist within a multidisciplinary care team in prescribing and managing treatments for tinea pedis and onychomycosis infections within this patient population. We believe that reducing the burden of these fungal infections in the context of the diabetic foot will help reduce DFU and DFI complications and their associated morbidity and mortality. Full article

Background: Raman spectroscopy is a well-known tool used in criminology, molecular biology, and histology. It is also applied to diagnose bone mineral disorders by taking advantage of the similarity of the structure of keratin and bone collagen. Raman spectroscopy can also be used in dermatology and diabetology. The purpose of the present review is to critically evaluate the available research about the use of Raman spectroscopy in the mentioned areas of medicine. Methodology: PubMed was searched for peer-reviewed articles on the subject of use of Raman spectroscopy in bone mineral disorders, dermatology, and diabetes mellitus. Results: Nail keratin and bone collagen are related structural proteins that require disulfide bond for structural stability. Therefore, Raman spectroscopy of keratin may have potential as a diagnostic tool for screening bone quality and distinguishing patients at risk of fracture for reasons different from low bone mineral density (BMD) in the adult women population. Raman spectroscopy can also investigate the changes in keratin’s structure in nails affected by onychomycosis and distinguish between healthy and onychomycosis nail samples. It could also reduce the need for nail biopsy by distinguishing between dermatophytic and non-dermatophytic agents of onychomycosis. Additionally, Raman spectroscopy could expedite the diagnostic process in psoriasis (by assessing the secondary structure of keratin) and in diabetes mellitus (by examining the protein glycation level). Conclusions: In adult populations, Raman spectroscopy is a promising and safe method for assessing the structure of fingernails. However, data are scarce in the pediatric population; therefore, more studies are required in children. Full article

People living with HIV (PLWH) display altered gut epithelium that allows for the translocation of microbial products, contributing to systemic immune activation. Although there are numerous studies which examine the gut bacterial microbiome in PLWH, few studies describing the fungal microbiome, or the mycobiome, have been reported. Like the gut bacterial microbiome, the fungal microbiome and its by-products play a role in maintaining the body’s homeostasis and modulating immune function. We conducted a prospective study to assess the effects of oral terbinafine, an antifungal agent widely used against onychomycosis, on gut permeability and microbiome composition in ART-treated PLWH (trial registration: ChiCTR2100043617). Twenty participants completed all follow-up visits. During terbinafine treatment, the levels of the intestinal fatty acid binding protein (I-FABP) significantly increased, and the levels of interleukin-6 (IL-6) significantly decreased, from baseline to week 12. Both markers subsequently returned to pre-treatment levels after terbinafine discontinuation. After terbinafine treatment, the abundance of fungi decreased significantly, while the abundance of the bacteria did not change. After terbinafine discontinuation, the abundance of fungi returned to the levels observed pre-treatment. Moreover, terbinafine treatment induced only minor changes in the composition of the gut bacterial and fungal microbiome. In summary, oral terbinafine decreases fungal microbiome abundance while only slightly influencing gut permeability and microbial translocation in ART-treated PLWH. This study’s findings should be validated in larger and more diverse studies of ART-treated PLWH; our estimates of effect size can be used to inform optimal sample sizes for future studies. Full article

Introda significant: Onychomycosis is the most common nail disorder seen in clinical practice, and it may have significant impact on patient quality of life. Understanding risk factors for onychomycosis may help to devise screening and treatment guidelines for populations that are more susceptible to this infection. Using a national database, we aimed to explore associations between onychomycosis and age, sex, and underlying medical conditions, as well as to examine current onychomycosis treatment trends. Materials and Methods: We performed a nested, matched, case–control study of patients in the All of Us database aged ≥ 18 years (6 May 2018–1 January 2022). Onychomycosis cases were identified using International Classification of Diseases (ICD) and Systematized Nomenclature of Medicine (SNOMED) diagnostic codes (ICD-9 110.1, ICD-10 B35.1, SNOMED 414941008). Demographic information (i.e., age, sex, and race), treatments, and co-diagnoses for onychomycosis patients and case–controls were recorded. Wald’s test applied to multivariate logistic regression was used to calculate odds ratios and p-values between onychomycosis and co-diagnoses. Additionally, 95% confidence intervals were calculated with a proportion test. Results: We included 15,760 onychomycosis patients and 47,280 matched controls. The mean age of onychomycosis patients was 64.9 years, with 54.2% female, 52.8% Non-Hispanic White, 23.0% Black, 17.8% Hispanic, and 6.3% other, which was similar to controls. Patients with onychomycosis vs. controls were more likely to have a co-diagnosis of obesity (46.4%, OR 2.59 [2.49–2.69]), tinea pedis (21.5%, OR 10.9 [10.1–11.6]), peripheral vascular disease (PVD) (14.4%, OR 3.04 [2.86–3.24]), venous insufficiency (13.4%, OR 3.38 [3.15–3.59]), venous varices (5.6%, OR 2.71 [2.47–2.97]), diabetes mellitus (5.6%, OR 3.28 [2.98–3.61]), and human immunodeficiency virus (HIV) (3.5%, OR 1.8 [1.61–2.00]) (p < 0.05, all). The most frequently prescribed oral and topical medications were terbinafine (20.9%) and ciclopirox (12.4%), respectively. The most common therapeutic procedure performed was debridement (19.3%). Over the study period, ciclopirox prescriptions (Spearman correlation 0.182, p = 0.0361) and fluconazole prescriptions increased (Spearman correlation 0.665, p = 2.44 × 10⁻⁴), and griseofulvin (Spearman correlation −0.557, p = 0.0131) and itraconazole prescriptions decreased (Spearman correlation −0.681, p = 3.32 × 10⁻⁶). Conclusions: Our study demonstrated that age, obesity, tinea pedis, PVD, venous insufficiency, diabetes mellitus, and HIV were significant risk factors for onychomycosis. In addition, the most frequent oral and topical onychomycosis medications prescribed were terbinafine and ciclopirox, likely reflective of efficacy and cost considerations. Identifying and managing these risk factors is essential to preventing onychomycosis’ primary infections and recurrences and improving treatment efficacy. Full article

Onychomycosis is a common nail infection. Terbinafine-resistant dermatophyte infections pose an emerging global public health concern, but few cases have been described in the United States. We retrospectively reviewed and characterized clinical, histopathological, and mycological features of patients with mycologically confirmed onychomycosis who failed oral terbinafine treatment for onychomycosis at a U.S. academic nail referral center and ascertained for terbinafine-resistant isolates. During 1 June 2022–31 January 2023 at Weill Cornell Medicine in New York City, USA, 96 patients with mycologically confirmed onychomycosis were treated with oral terbinafine. Among 64 patients with adequate follow-up, 36 had clinical or complete cure. Of 28 patients who failed treatment, 17 underwent terbinafine resistance testing. Trichophyton rubrum with terbinafine resistance-conferring mutations was isolated from two patients. Overall, terbinafine failures for onychomycosis were relatively common, with some cases associated with terbinafine-resistant T. rubrum infections. These findings underscore the need for a clinical awareness of this emerging problem and public health efforts to monitor and prevent spread. We highlight the importance of diagnostic testing and species identification for onychomycosis patients and the increasingly important role of fungal identification and susceptibility testing to guide therapy. Full article

Fusarium are uncommon but important pathogenic organisms; they cause non-dermatophyte mould (NDM) onychomycosis. Patients typically respond poorly to treatment owing to Fusarium’s native resistance to multiple antifungal drugs. However, epidemiological data for Fusarium onychomycosis are lacking in Taiwan. We retrospectively reviewed the data of 84 patients with positive Fusarium nail sample cultures at Chang Gung Memorial Hospital, Linkou Branch between 2014 and 2020. We aimed to investigate the clinical presentations, microscopic and pathological characteristics, antifungal susceptibility, and species diversity of Fusarium in patients with Fusarium onychomycosis. We enrolled 29 patients using the six-parameter criteria for NDM onychomycosis to determine the clinical significance of Fusarium in these patients. All isolates were subjected to species identification by sequences and molecular phylogeny. A total of 47 Fusarium strains belonging to 13 species in four different Fusarium species complexes (with Fusarium keratoplasticum predominating) were isolated from 29 patients. Six types of histopathology findings were specific to Fusarium onychomycosis, which may be useful for differentiating dermatophytes from NDMs. The results of drug susceptibility testing showed high variation among species complexes, and efinaconazole, lanoconazole, and luliconazole showed excellent in vitro activity for the most part. This study’s primary limitation was its single-centre retrospective design. Our study showed a high diversity of Fusarium species in diseased nails. Fusarium onychomycosis has clinical and pathological features distinct from those of dermatophyte onychomycosis. Thus, careful diagnosis and proper pathogen identification are essential in the management of NDM onychomycosis caused by Fusarium sp. Full article

Onychomycosis is a fungal disease of the nail that is found worldwide and is difficult to diagnose accurately. This study used metagenomics to investigate the microbiology of 18 clinically diagnosed mycotic nails and two normal nails for fungi and bacteria using the ITS2 and 16S loci. Four mycotic nails were from Bass Coast, six from Melbourne Metropolitan and eight from Shepparton, Victoria, Australia. The mycotic nails were photographed and metagenomically analysed. The ITS2 sequences for T. rubrum and T. interdigitale/mentagrophytes averaged over 90% of hits in 14/18 nails. The high abundance of sequences of a single dermatophyte, compared to all other fungi in a single nail, made it the most likely infecting agents (MLIA). Trichophyton rubrum and T. interdigitale/mentagrophytes were found in Bass Coast and Shepparton while only T. interdigitale/mentagrophytes was found in Melbourne. Two nails with T. interdigitale/mentagrophytes mixed with high abundance non-dermatophyte moulds (NDMs) (Aspergillus versicolor, Acremonium sclerotigenum) were also observed. The two control nails contained chiefly Fusarium oxysporum and Malassezia slooffiae. For bacteria, Staphylococcus epidermidis was in every nail and was the most abundant, including the control nails, with an overall mean rate of 66.01%. Rothia koreensis, Corynebacterium tuberculostearicum, and Brevibacterium sediminis also featured. Full article

The current study aimed to develop chitosan nanoparticles (CSNP) loaded poloxamer 407 (P407) gel formulation for transungual delivery of terbinafine HCl (TBN). TBN-CSNP were prepared by nanoprecipitation method and optimized by face-centered central composite design (FCCCD). Optimized TBN-CSNP formulation exhibited a spherical shape with hydrodynamic diameter; zeta potential and entrapment efficiency (EE) of 229 ± 5 nm; 37 ± 1.5 mV; and 75 ± 2% respectively. The solid state of TBN and its compatibility with formulation ingredients were confirmed through XRD and FTIR analysis respectively. TBN-CSNP loaded P407 gel exhibited pseudoplastic rheological behavior having a spreadability of 11 ± 2 g·cm/s. The washability study showed that 40 ± 2% of the gel was eroded after washing 12 times. Drug release from TBN-CSNP- and TBN-CSNP-loaded gel was 84 ± 5% and 57 ± 3%, respectively. The cumulative quantity of TBN permeated from TBN-CSNP-loaded P407 gel and TBN-loaded P407 gel was 25 ± 8 and 27 ± 4 µg/cm², respectively. The nail uptake study showed that 3.6 ± 0.7 and 2.1 ± 0.3 µg of rhodamine was uptaken by the nail following 2 h topical application of TBN-CSNP loaded P407 gel and TBN loaded P407 gel, respectively. Hence, the developed CSNP-based P407 gel formulation can be a potential carrier for transungual delivery of TBN to topically treat onychomycosis. Full article

The revolutionary development of green technology, such as ultrasound-assisted extraction, has had a significant impact on the extraction methods of natural compounds with pharmacological potential. These methods are considered green because they are environmentally friendly, minimizing the use of toxic solvents, energy consumption, and CO₂ generation. Antimicrobial resistance is a global public health problem. Pathogens of dermatological and nosocomial relevance are more frequent because they are resistant to antimicrobials. Agave nuusaviorum leaves are used in traditional medicine to treat onychomycosis and inflammatory processes. Here, the antimicrobial activity of hydroethanolic extract of A. nuusaviorum leaves obtained by ultrasound-assisted extraction was evaluated. The antimicrobial activity was tested against 14 pathogens with dermatological and nosocomial relevance by the agar diffusion technique. The extract exhibited an antimicrobial effect on all microorganisms tested, showing inhibition zones of 9–16 mm for Staphylococcus aureus, Candida albicans, Candida parapsilosis, and eleven isolates of Trichophyton. The extract’s minimum inhibitory concentration ranged between 0.5 mg/mL for Staphylococcus aureus, 0.25–1 mg/mL for yeast, and 0.4–1.25 mg/mL for molds. The phytochemical screening revealed the presence of terpenes, phenolic acids, tannins, carbohydrates, and steroids in the extract. The results showed that A. nuusaviorum leaves have broad-spectrum antimicrobial potential. Full article

As regulatory and technical landscapes for pharmaceutical formulation development are rapidly evolving, a risk-management approach using multivariate analysis is highly essential for designing a product with requisite critical quality attributes (CQA). Efinaconazole, a newly approved poorly water-soluble antifungal triazole drug has poor permeability. Spanlastics, new-generation surfactant nanovesicles, being fluidic, help improve the permeability of drugs. Therefore, we optimized efinaconazole spanlastics using the concepts of Formulation-by-Design (FbD) and explored the feasibility of transungual delivery for the management of onychomycosis. Using the Ishikawa fishbone diagram, the risk factors that may have an impact on the CQA of efinaconazole spanlastic vesicles were identified. Application of the Plackett–Burman experimental design facilitated the screening of eight different formulation and process parameters influencing particle size, transmittance, relative deformability, zeta potential, entrapment efficiency, and dissolution efficiency. With the help of Pareto charts, the three most significant factors were identified, viz., vesicle builder (Span), edge activator (Tween), and mixing time. The levels of these three critical variables were optimized by FbD to reduce the particle size and maximize the transparency, relative deformability, encapsulation efficiency, and dissolution efficiency of efinaconazole spanlastic nanovesicles. Bayesian and Lenth’s analysis and mathematical modeling of the experimental data helped to quantify the critical formulation attributes required for getting the formulation with optimum quality features. The optimized efinaconazole-loaded spanlastic vesicles had a particle size of 197 nm, transparency of 91%, relative deformability of 12.5 min, and dissolution efficiency of 81.23%. The spanlastic formulation was incorporated into a gel and explored ex vivo for transungual delivery. This explorative study provides an example of the application of principles of risk management, statistical multivariate analysis, and the FbD approach in developing efinaconazole spanlastic nanovesicles. Full article

An overview of the long-established methods of diagnosing onychomycosis (potassium hydroxide testing, fungal culture, and histopathological examination) is provided followed by an outline of other diagnostic methods currently in use or under development. These methods generally use one of two diagnostic techniques: visual identification of infection (fungal elements or onychomycosis signs) or organism identification (typing of fungal genus/species). Visual diagnosis (dermoscopy, optical coherence tomography, confocal microscopy, UV fluorescence excitation) provides clinical evidence of infection, but may be limited by lack of organism information when treatment decisions are needed. The organism identification methods (lateral flow techniques, polymerase chain reaction, MALDI-TOF mass spectroscopy and Raman spectroscopy) seek to provide faster and more reliable identification than standard fungal culture methods. Additionally, artificial intelligence methods are being applied to assist with visual identification, with good success. Despite being considered the ‘gold standard’ for diagnosis, clinicians are generally well aware that the established methods have many limitations for diagnosis. The new techniques seek to augment established methods, but also have advantages and disadvantages relative to their diagnostic use. It remains to be seen which of the newer methods will become more widely used for diagnosis of onychomycosis. Clinicians need to be aware of the limitations of diagnostic utility calculations as well, and look beyond the numbers to assess which techniques will provide the best options for patient assessment and management. Full article