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ACS Biomaterials Science & Engineering May 2024Persistent foot odor and itchiness are common symptoms of tinea pedis, significantly disrupting the daily life of those affected. The cuticular barrier at the site of...
Persistent foot odor and itchiness are common symptoms of tinea pedis, significantly disrupting the daily life of those affected. The cuticular barrier at the site of the tinea pedis is thickened, which impedes the effective penetration of antifungal agents. Additionally, fungi can migrate from the skin surface to deeper tissues, posing challenges in the current clinical treatment for tinea pedis. To effectively treat tinea pedis, we developed a platform of bilayer gelatin methacrylate (GelMA) microneedles (MNs) loaded with salicylic acid (SA) and FK13-a1 (SA/FK13-a1@GelMA MNs). SA/FK13-a1@GelMA MNs exhibit pH- and matrix metalloproteinase (MMP)-responsive properties for efficient drug delivery. The MNs are designed to deliver salicylic acid (SA) deep into the stratum corneum, softening the cuticle and creating microchannels. This process enables the antibacterial peptide FK13-a1 to penetrate through the stratum corneum barrier, facilitating intradermal diffusion and exerting antifungal and anti-inflammatory effects. In severe cases of tinea pedis, heightened local pH levels and MMP activity further accelerate drug release. Our research demonstrates that SA/FK13-a1@GelMA MNs are highly effective against , , and . They also reduced stratum corneum thickness, fungal burden, and inflammation in a guinea pig model of tinea pedis induced by . Furthermore, it was discovered that SA/FK13-a1@GelMA MNs exhibit excellent biocompatibility. These findings suggest that SA/FK13-a1@GelMA MNs have significant potential for the clinical treatment of tinea pedis as well as other fungal skin disorders.
Topics: Tinea Pedis; Animals; Hydrogen-Ion Concentration; Needles; Antifungal Agents; Matrix Metalloproteinases; Humans; Drug Delivery Systems; Guinea Pigs; Gelatin; Methacrylates
PubMed: 38659287
DOI: 10.1021/acsbiomaterials.4c00305 -
Anais Brasileiros de Dermatologia 2024
Topics: Humans; Dermoscopy; Eczema; Tinea Pedis; Psoriasis; Hand Dermatoses; Female; Male; Adult; Middle Aged
PubMed: 38658237
DOI: 10.1016/j.abd.2023.05.008 -
BMJ Open Apr 2024Diabetic foot ulcers are feared complications of diabetes mellitus (DM), requiring extensive treatment and hospital admissions, ultimately leading to amputation and...
INTRODUCTION
Diabetic foot ulcers are feared complications of diabetes mellitus (DM), requiring extensive treatment and hospital admissions, ultimately leading to amputation and increased mortality. Different factors contribute to the development of foot ulcers and related complications. Onychomycosis, being more prevalent in patients with diabetes, could be an important risk factor for developing ulcers and related infections. However, the association between onychomycosis and diabetic complications has not been well studied in primary care.
RESEARCH DESIGN AND METHODS
To determine the impact of onychomycosis on ulcer development and related complications in patients with diabetes in primary care, a longitudinal cohort study was carried out using routine care data from the Extramural Leiden University Medical Center Academic Network. Survival analyses were performed through Cox proportional hazards models with time-dependent covariates.
RESULTS
Data from 48 212 patients with a mean age of 58 at diagnosis of DM, predominantly type 2 (87.8%), were analysed over a median follow-up of 10.3 years. 5.7% of patients developed an ulcer. Onychomycosis significantly increased the risk of ulcer development (HR 1.37, 95% CI 1.13 to 1.66), not affected by antimycotic treatment, nor after adjusting for confounders (HR 1.23, 95% CI 1.01 to 1.49). The same was found for surgical interventions (HR 1.54, 95% CI 1.35 to 1.75) and skin infections (HR 1.48, CI 95% 1.28 to 1.72), again not affected by treatment and significant after adjusting for confounders (HR 1.32, 95% CI 1.16 to 1.51 and HR 1.27, 95% CI 1.10 to 1.48, respectively).
CONCLUSIONS
Onychomycosis significantly increased the risk of ulcer development in patients with DM in primary care, independently of other risk factors. In addition, onychomycosis increased the risk of surgeries and infectious complications. These results underscore the importance of giving sufficient attention to onychomycosis in primary care and corresponding guidelines. Early identification of onychomycosis during screening and routine care provides a good opportunity for timely recognition of increased ulcer risk.
Topics: Humans; Onychomycosis; Female; Male; Middle Aged; Longitudinal Studies; Netherlands; Diabetic Foot; Aged; Risk Factors; General Practice; Diabetes Mellitus, Type 2; Proportional Hazards Models; Adult; Primary Health Care
PubMed: 38658014
DOI: 10.1136/bmjopen-2023-076441 -
Current Microbiology Apr 2024Aspergillus fumigatus and Fusarium solani infections have become severe health threat; both pathogens are considered a priority due to the increasing emergence of...
Aspergillus fumigatus and Fusarium solani infections have become severe health threat; both pathogens are considered a priority due to the increasing emergence of antifungal-resistant strains and high mortality rates. Therefore, the discovery of new therapeutic strategies has become crucial. In this study, we evaluated the antifungal and antivirulence effects of vanillin and tannic acid against Aspergillus fumigatus and Fusarium solani. The minimum inhibitory concentrations of the compounds were determined by the microdilution method in RPMI broth in 96-well microplates according to CLSI. Conidial germination, protease production, biofilm formation, and in vivo therapeutic efficacy assays were performed. The results demonstrated that vanillin and tannic acid had antifungal activity against Aspergillus fumigatus, while tannic acid only exhibited antifungal activity against Fusarium solani. We found that vanillin and tannic acid inhibited conidial germination and secreted protease production and biofilm formation of the fungal pathogens using sub-inhibitory concentrations. Besides, vanillin and tannic acid altered the fungal membrane permeability, and both compounds showed therapeutic effect against aspergillosis and fusariosis in an infection model in Galleria mellonella larvae. Our results highlight the antivirulence effect of vanillin and tannic acid against priority pathogenic fungi as a possible therapeutic alternative for human fungal infections.
Topics: Benzaldehydes; Fusarium; Tannins; Antifungal Agents; Microbial Sensitivity Tests; Biofilms; Aspergillus fumigatus; Animals; Aspergillosis; Virulence; Larva; Fusariosis; Spores, Fungal; Moths; Polyphenols
PubMed: 38656548
DOI: 10.1007/s00284-024-03678-w -
Anais Brasileiros de Dermatologia 2024
Topics: Humans; Terbinafine; Antifungal Agents; Treatment Outcome; Aspergillosis; Male; Dermatomycoses; Female; Middle Aged
PubMed: 38653610
DOI: 10.1016/j.abd.2023.07.011 -
CMAJ : Canadian Medical Association... Apr 2024
Topics: Humans; Tinea Capitis; Male; Alopecia; Child; Antifungal Agents
PubMed: 38649169
DOI: 10.1503/cmaj.231613 -
Cutis Mar 2024
Topics: Child; Humans; Antifungal Agents; Skin Diseases, Papulosquamous; Tinea Capitis
PubMed: 38648588
DOI: 10.12788/cutis.0984 -
Microbiology Spectrum Jun 2024Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against sp., both and in a murine model of...
UNLABELLED
Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against sp., both and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by . In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis.
IMPORTANCE
This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.
Topics: Cats; Animals; Itraconazole; Sporotrichosis; Antifungal Agents; Cat Diseases; Sporothrix; Drug Therapy, Combination; Hydrazones; Female; Male; Microbial Sensitivity Tests; Biofilms; Treatment Outcome
PubMed: 38647345
DOI: 10.1128/spectrum.03967-23 -
Mycopathologia Apr 2024The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small...
The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.
Topics: Humans; Male; Dermatomycoses; Skin; Trichophyton; Microscopy; Scrotum
PubMed: 38627263
DOI: 10.1007/s11046-024-00839-0 -
Expert Opinion on Pharmacotherapy Apr 2024The reports of resistance to antifungal agents used for treating onychomycosis and other superficial fungal infections are increasing. This rise in antifungal resistance... (Review)
Review
INTRODUCTION
The reports of resistance to antifungal agents used for treating onychomycosis and other superficial fungal infections are increasing. This rise in antifungal resistance poses a public health challenge that requires attention.
AREAS COVERED
This review explores the prevalence of dermatophytes and the current relationship between dermatophyte species, their minimum inhibitory concentrations (MICs) for terbinafine (an allylamine) and itraconazole (an azole), and various mutations prevalent in these species. The most frequently isolated dermatophyte associated with resistance in patients with onychomycosis and dermatophytosis was . However, emerged as the most prevalent isolate with mutations in the gene, exhibiting the highest MIC of 8 µg/ml for terbinafine and MICs of 8 µg/ml and ≥ 32 µg/ml for itraconazole.Overall, the most prevalent mutations were Phe397Leu, Leu393Phe, Ala448Thr, Phe397Leu/Ala448Thr, and Lys276Asn/Leu415Phe (relatively recent).
EXPERT OPINION
Managing dermatophyte infections requires a personalized approach. A detailed history should be obtained including details of travel, home and occupational exposure, and clinical examination of the skin, nails and other body systems. Relevant testing includes mycological examination (traditional and molecular). Additional testing, where available, includes MIC evaluation and detection of mutations. In case of suspected terbinafine resistance, itraconazole or voriconazole (less commonly) should be considered.
Topics: Antifungal Agents; Humans; Drug Resistance, Fungal; Microbial Sensitivity Tests; Tinea; Mutation; Arthrodermataceae; Terbinafine; Itraconazole; Onychomycosis
PubMed: 38623728
DOI: 10.1080/14656566.2024.2343079