Search Results (130)

Vulvovaginal candidiasis (VVC) is one of the most common superficial fungal infections affecting women. A particularly challenging issue is the treatment of recurrent vulvovaginal candidiasis (RVVC)—defined as ≥4 episodes of VVC within 12 months—which affects 5–8% of women with VVC. The development of VVC is influenced by many risk factors related to the host organism and behaviour, including disturbances in the vaginal microflora, hormonal fluctuations, diabetes, hygiene and sexual behaviour. Although C. albicans remains the primary species causing this infection, infections caused by other species, such as Nakaseomyces glabratus and Pichia kudriavzevii, are becoming increasingly common, partly due to the widespread use of azole antifungal drugs and growing drug resistance. Therefore, this publication focuses on a review of the newest literature concerning the epidemiology, diagnosis, current approaches to antifungal susceptibility testing and treatment according to global guidelines. According to the literature, precise species identification and drug susceptibility testing are crucial to avoid therapeutic errors and drug resistance. Moreover, new antifungal drugs such as tetrazoles (oteseconazole) and triterpenoids (ibrexafungerp) are entering clinical practice, offering high efficacy against resistant strains. Probiotics used as adjuvant therapy help restore the homeostasis of the vaginal microbiome; however, due to inconsistent evidence, they are currently not included in treatment recommendations. Full article

Background: Tinea capitis remains one of the most common superficial fungal infections in children worldwide and represents an important public health concern due to its high prevalence, potential complications, and changing epidemiology. This study aimed to characterize the epidemiological trends and etiological distribution of tinea capitis across the Americas through a systematic review of the available literature. Methods: A systematic search was conducted in MEDLINE (PubMed), Scopus, SCILIT, and SciELO following PRISMA guidelines. A total of 250 records were identified, of which 75 duplicates were removed. After title and abstract screening and eligibility assessment, 90 studies were included. Observational studies, prevalence studies, case series, and case reports reporting epidemiological or etiological data on tinea capitis in countries of the American continent were considered eligible. Methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. No formal certainty-of-evidence assessment or meta-analysis was performed due to the descriptive nature and heterogeneity of the included studies. This review was not prospectively registered. Results: The 90 included studies comprised 506,086 reported cases of tinea capitis. Marked regional differences were identified in the distribution of dermatophyte species. Trichophyton tonsurans predominated in North America and several Caribbean countries, whereas Microsporum canis was the most frequently reported etiological agent in much of South America and parts of Central America, suggesting an important role of zoonotic transmission in these regions. Variations in prevalence and species distribution were also associated with geographic, socioeconomic, and demographic factors. Overall, the included studies demonstrated low-to-moderate methodological risk of bias. Conclusions: These findings demonstrate substantial heterogeneity in the epidemiology of tinea capitis throughout the Americas and highlight the importance of continuous surveillance, accurate mycological diagnosis, and region-specific public health strategies to improve disease control and guide appropriate therapeutic interventions. Full article

Candida infections represent a major global public health challenge and remain among the most common opportunistic fungal infections worldwide. Although Candida albicans remains the predominant pathogen, the incidence of infections caused by non-albicans species, particularly Candidozyma auris, has increased substantially in recent years. Candida infections range from superficial mucocutaneous disease to invasive life-threatening infections associated with high morbidity and mortality. In addition to clinical burden, growing evidence indicates a substantial negative impact on health-related quality of life, particularly among patients with recurrent vulvovaginal candidiasis and chronic fungal infections. Full article

Sexually transmitted infections (STIs) remain a global health burden. Beyond classical pathogens, dermatophytes are increasingly identified within sexually linked transmission networks. Genital dermatophytosis is a superficial fungal infection of the genital area, primarily caused by anthropophilic and zoophilic dermatophytes. Recently, Trichophyton mentagrophytes genotype VII and Trichophyton indotineae have emerged as clinically significant dermatophytes, increasingly linked to human-to-human and sexually associated transmission within highly interconnected sexual networks. These infections are often marked by inflammatory, persistent, and treatment-refractory presentations, with prominent genital involvement and rising antifungal resistance—particularly to terbinafine—posing growing diagnostic and therapeutic challenges. Doxycycline post-exposure prophylaxis (Doxy-PEP) has recently emerged as a novel preventive strategy for bacterial STIs, involving the administration of 200 mg doxycycline within 24–72 h after activities associated with increased infection exposure, particularly among men who have sex with men (MSM) and transgender women. While effective in reducing infections such as syphilis and chlamydia, its broader implementation raises concerns regarding antimicrobial resistance. Chemsex is an increasingly prevalent behavioural phenomenon, defined as the intentional use of psychoactive substances during sexual activity to enhance or prolong the experience, particularly among MSM. It is associated with multiple adverse effects, including increased STI transmission, substance dependence, drug toxicity, psychological disturbances, and significant challenges in treatment adherence and healthcare engagement. This review aims to provide a comprehensive and clinically oriented overview of emerging trends in STIs, with a particular focus on dermatophyte infections as pathogens with potential sexually associated transmission, alongside evolving prevention strategies and behavioral factors influencing transmission. Full article

Dermatophytosis remains one of the most prevalent superficial fungal infections worldwide and is increasingly encountered as a persistent or difficult-to-treat syndrome. A major clinical problem is that apparent treatment failure is often attributed to antifungal resistance, although many cases are instead driven by diagnostic uncertainty, corticosteroid-modified disease, reinfection, inadequate exposure, poor adherence, and limited drug delivery within keratinized tissues. This narrative review was developed to clarify the distinction between true antifungal resistance and clinical recalcitrance, with particular attention to terbinafine-resistant Trichophyton species, Trichophyton indotineae, tinea incognito, onychomycosis, dermatophytoma, and high-barrier skin and nail infections. We synthesized peer-reviewed literature and guideline-level evidence addressing epidemiology, molecular mechanisms of resistance, clinical phenotypes of recalcitrance, diagnostic escalation, therapeutic decision-making, and antifungal delivery in keratinized tissues. The review contributes a dermatology-centered conceptual framework in which persistent dermatophytosis is interpreted through both microbiological resistance and modifiable recalcitrance drivers. This approach emphasizes confirmation of fungal disease when indicated, phenotypic and anatomic classification, avoidance of inappropriate corticosteroid combinations, optimization of dose, duration, vehicle, and adherence, measures to improve drug access and reduce protected fungal burden in high-barrier disease, and prevention of reinfection from reservoirs. The proposed framework may support more rational antifungal use and reduce unnecessary escalation; however, it is based on narrative synthesis rather than a systematic review or prospective validation. Additional studies are needed to determine how such structured clinical approaches affect clinical outcomes, relapse rates, antifungal exposure, and resistance emergence in real-world dermatology practice. Full article

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

Background/Objective: Topical therapy remains a cornerstone in managing fungal infections due to the deep-seated nature of the pathogens and the persistence of the disease. Ketoconazole (KTZ) is a broad-spectrum antifungal agent, but its highly lipophilic nature presents considerable challenges in developing effective topical formulations. Additionally, oral KTZ has been subject to labeling restrictions and market withdrawal due to its association with severe hepatic adverse effects. This study was conducted to design, optimize, and evaluate KTZ-loaded nanolipid carriers (NLCs; KTZ-NLCs) as a delivery platform that could improve cutaneous bioavailability and enhance antifungal activity. Methods: The optimized KTZ-NLCs were further incorporated into a mucoadhesive system (KTZ-NLCs-C) through the inclusion of Carbopol^® 940 NF, aiming to improve the retention of the formulation on the skin surface. NLCs were characterized in terms of their physical appearance, particle size, polydispersity index, zeta potential, pH, viscosity, drug content, and entrapment efficiency. The optimized KTZ-NLC and KTZ-NLCs-C formulations were subsequently assessed for in vitro drug release, ex vivo skin permeation and deposition, as well as in vivo skin irritation. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KTZ over 24 h. The ex vivo transdermal flux and permeability coefficient of KTZ from the lead KTZ-NLCs-C formulation were approximately 2.8-fold greater than those achieved with the marketed cream formulation. The in vivo skin irritation studies indicate that NLC-based formulations are suitable for topical applications. The lead formulation was stable for 90 days (the final time point evaluated) under refrigerated and room-temperature storage conditions. Conclusions: These findings suggest that the NLC-based system is a promising platform for the topical delivery of KTZ and has the potential to enhance the therapeutic outcomes for patients with superficial fungal infections. Full article

Background: Dermatological diseases account for a substantial share of primary-care visits, yet many are referred to secondary or tertiary services. A notable proportion of dermatology outpatient visits may instead be manageable within primary care. We evaluated whether patients assessed at the tertiary level could have been managed in primary care, in order to inform referral optimization. Methods: In this retrospective, cross-sectional study, the records of 400 patients who presented to the dermatology outpatient clinic of a city hospital in Istanbul between May, and July 2025 were analyzed. Each case was independently classified by three multidisciplinary commissions; each commission comprised a dermatologist, a family medicine specialist, and a general practitioner. Each commission produced a single panel-level management decision per case, and inter-commission agreement across the three commissions was assessed with Fleiss’ kappa. Results: Of the 400 patients, 58.8% were female and the mean age was 31.0 ± 17.6 years; 27.5% (n = 110) were pediatric (aged 0–18 years). Overall, 51.5% of cases were judged manageable in primary care (27.5% by a family physician directly and 24.0% with teledermatology support); this was 55.5% in pediatric and 50.0% in adult patients. Only 17.8% of patients had consulted a family physician in the 7 days before attendance. The most frequent diagnoses were acne, dermatitis, and superficial fungal infections. Inter-commission agreement was moderate overall (κ = 0.430; p < 0.001) and lower in pediatric (κ = 0.312) than adult (κ = 0.471) cases. Conclusions: A substantial proportion of tertiary dermatology visits could plausibly be managed in primary care. Realizing this potential depends primarily on strengthening primary-care dermatology capacity, with teledermatology serving as one structured, supportive pathway. Full article

Fungal infections represent an escalating global health challenge due to their increasing incidence, the emergence of multidrug-resistant pathogens, and the limited development of new antifungal agents. Therapeutic efficacy is compromised by mutations in drug targets, overexpression of efflux pumps, alterations in the ergosterol biosynthetic pathway, biofilm-associated tolerance, and extensive genomic plasticity. The growing prevalence of antifungal resistance and the limited availability of effective therapeutic options highlight the urgent need to strengthen epidemiological surveillance and accelerate research into innovative therapeutic strategies. In this review, we discuss the potential of lipid-based drug delivery systems (LDDSs) as a versatile strategy to optimize antifungal administration and overcome resistance mechanisms. Liposomes (LPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid nanoparticles (LNPs) offer high biocompatibility, efficient encapsulation of hydrophobic compounds, structural stability, and controlled drug release. Their nanoscale properties facilitate penetration into biofilms, promote intracellular uptake, and reduce the impact of efflux-mediated drug extrusion, thereby improving cellular penetration and circumventing resistance pathways. In addition, LDDSs increase bioavailability, reduce toxicity, and promote drug accumulation within poorly accessible tissue compartments. Overall, LDDSs represent a promising approach to expand the therapeutic arsenal against both superficial and invasive fungal infections, particularly those caused by multidrug-resistant pathogens. Full article

Fungal infections remain a major and growing global health concern, particularly in immunocompromised populations and in settings where antifungal resistance is increasing. Imidazole antifungals continue to play an important role in the treatment of superficial and mucocutaneous mycoses because they inhibit lanosterol 14α-demethylase (CYP51), a key enzyme in ergosterol biosynthesis. This mechanism disrupts fungal membrane integrity and underlies their clinical utility. However, the effectiveness of imidazoles is increasingly limited by resistance mechanisms such as CYP51 mutations, efflux pump overexpression, and biofilm-associated tolerance. In parallel, several biopharmaceutical constraints, including poor aqueous solubility, limited tissue penetration, short residence time, and variable local drug exposure, further reduce therapeutic performance. This review critically examines the medicinal chemistry, mechanism of action, and resistance biology of imidazole antifungals, while also highlighting the role of pharmacokinetic and pharmacodynamic limitations in treatment failure. Particular attention is given to emerging drug delivery approaches, including lipid-based systems, vesicular carriers, nanocarriers, and other advanced topical formulations, which are being developed to improve solubility, enhance tissue retention, and sustain antifungal exposure at the site of infection. By integrating resistance mechanisms with formulation science, the review provides a translational perspective on how imidazole antifungals may be optimized for improved clinical utility and resistance management. Full article

Background: Superficial fungal infections caused by dermatophyte and non-dermatophyte species are increasing globally. While several comorbid diseases and risk factors have been associated with fungal infections at the individual level, their epidemiological relationships at the population level remains poorly characterized. Objective: We aimed to examine population-level associations between the burden of superficial fungal infections and selected comorbid conditions and risk factors, stratified by age, sex and country. Methods: We obtained years lived with disability (YLDs) for superficial fungal infections, diabetes, psoriasis, and atopic dermatitis and summary exposure values (SEVs) for high body mass index (BMI) and high alcohol intake from Global Burden of Disease Study 2023. Data were obtained for Australia, Brazil, the United Kingdom and the United States for males and females younger than 20 years, 20 to 54 years and 55+ years old. Pearson correlation coefficients were calculated between fungal infection YLDs and each comorbid condition (YLDs) and risk factor (SEVs). Results: Significant positive correlations were observed between superficial fungal infection burden and diabetes (R = 0.6–0.98), high BMI (R = 0.75–0.95), psoriasis (R = 0.59–0.96), and atopic dermatitis (R = 0.51–0.93) in older adults (55 years+). Correlations with high alcohol consumption were more variable across regions and sex. In young–middle-aged adults (20–54 years), moderate-to-strong correlations (R ~ 0.8–0.9) were observed, although patterns were less consistent across countries. In individuals < 20 years, associations were generally weaker, with some positive correlations observed for atopic dermatitis (R = 0.4–0.7) in select countries. Conclusions: The findings demonstrate population-level associations between superficial fungal infections and metabolic, inflammatory, and behavioural risk factors, with stronger correlations observed in older age groups. These patterns may reflect shared demographic, epidemiologic, and clinical patterns across conditions. 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

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

Among Candida species, several are major opportunistic fungal pathogens capable of causing a wide spectrum of infections, ranging from superficial mucosal conditions to severe systemic diseases. Their success as human pathogens is largely due to their ability to rapidly adapt to diverse host environments and develop resistance to antifungal agents. Experimental evolution provides a powerful framework for understanding these adaptive processes by observing evolutionary change in real-time. Although most studies rely on in vitro systems and a limited set of Candida species, there is strong evidence that genome plasticity, including aneuploidy, loss of heterozygosity, and copy number variation, plays a central role in driving rapid adaptation. Experimental evolution has also been applied to study the dynamics of antifungal resistance, particularly to azoles, although relatively fewer studies have explored resistance to echinocandins and polyenes. This review summarizes current knowledge on experimental evolution in pathogenic Candida species, with a focus on genome plasticity, adaptation to host-imposed stress, and particularly on the emergence of antifungal resistance. It also identifies critical research gaps, including the need for broader species coverage, investigation of underexplored antifungal classes, and evaluation of combined therapies. A deeper understanding of these dynamics is essential to improve antifungal strategies and counter the growing threat of drug-resistant Candida spp. infections. Full article

Nystatin is a polyene macrolide antibiotic with broad-spectrum antifungal activity and serves as a key therapeutic agent for superficial fungal infections. This review systematically elaborates on its multicomponent chemical nature, its mechanism of action targeting ergosterol, and highlights the potential adverse effects, such as cardiotoxicity, associated with impurities like RT6 (albonoursin). The fundamental analytical techniques for quality control are outlined. Furthermore, the clinical applications and combination therapy strategies of nystatin in treating oral diseases, vaginitis, and otitis externa are summarized in detail. Regarding biosynthesis, the assembly mechanism of nystatin A₁ via the type I polyketide synthase pathway and its subsequent modification processes are thoroughly discussed. Emphasis is placed on the latest advances and potential of gene-editing technologies, particularly CRISPR/Cas9, in the targeted knockout of genes responsible for toxic components and in optimizing production strains to enhance nystatin yield and purity. Finally, this review prospects the future development of nystatin towards improved safety and efficacy through structural optimization, innovative delivery systems, and synthetic biology strategies, aiming to provide a reference for its further research and clinical application. Full article