Fungal infections represent a significant global health challenge, encompassing highly prevalent superficial mycoses and increasingly frequent invasive fungal diseases associated with substantial morbidity and mortality. Conventional antifungal therapies are often limited by poor skin and nail penetration, suboptimal bioavailability, systemic toxicity, and the emergence of antifungal resistance, resulting in prolonged treatment regimens and high recurrence rates. Ethosomal drug delivery systems, composed of phospholipids and high ethanol content, have emerged as advanced vesicular carriers capable of overcoming these limitations through enhanced membrane fluidization, vesicle deformability, and efficient transdermal and mucosal penetration. This review critically examines the concept, composition, and penetration mechanisms of ethosomes with a focused emphasis on antifungal drug delivery. Reported ethosomal formulations of azoles, polyenes, allylamines, echinocandins, and herbal antifungals are systematically analyzed with respect to physicochemical properties, skin and nail permeation, antifungal efficacy, and safety outcomes. Quantitative evidence from in vitro, ex vivo, in vivo, and emerging clinical studies demonstrates superior drug deposition, faster fungal clearance, reduced systemic toxicity, and improved patient compliance compared to conventional and other vesicular systems. Overall, ethosomal drug delivery represents a promising and clinically relevant approach for improving the management of both superficial and systemic fungal infections. However, further large-scale clinical studies and regulatory standardization are required for successful clinical translation. Clinically, ethosomes should therefore be interpreted as an indication-specific enabling platform rather than an immediate replacement for effective standard antifungal therapy, because routine superficial infections are often controlled with existing topical or oral agents and the therapeutic landscape is evolving through recently approved or late-stage antifungal compounds and adjunctive immunotherapeutic approaches.
This study aimed to elucidate the cellular and molecular mechanisms underlying the interaction between macrophages and Trichophyton rubrum in the presence of a curcumin analog. RNA-seq and transcriptomic analyses of mRNA and microRNAs using the co-culture model revealed that the presence of T. rubrum strongly modulates gene expression in THP-1 cells, with dozens of genes being upregulated or downregulated (involving signaling pathways, cell communication, inflammation, and immune response). Additionally, the co-culture model can be used to evaluate the response of macrophages infected with T. rubrum in the presence of novel antifungal molecules. Trichophyton rubrum is the primary causative agent of superficial mycoses worldwide; however, it has been increasingly associated with invasive infections, particularly in immunocompromised and diabetic patients. Curcumin analogs exhibit promising antifungal and anti-inflammatory activity. The invasive infectious process involves initial contact between the pathogen and the host, pathogen adherence, tissue invasion, and activation of the immune response. Nevertheless, this process remains incompletely understood, especially in the presence of new antifungal compounds. A co-culture model was established using previously germinated and heat-inactivated T. rubrum conidia in contact with THP-1 exposed to curcumin analog for 24 h. This study demonstrated that the synthetic curcuminoid 2102 exhibits potent antifungal activity against T. rubrum, with low minimum inhibitory concentration and reduced cytotoxicity in THP-1-derived macrophages. In co-culture, curcuminoid was able to modulate the inflammatory response, significantly decreasing the release of IL-1β, IL-12, and TNF-α, while promoting a dose-dependent increase in the production of reactive oxygen species, suggesting a dual role in both controlling fungal growth and enhancing cellular defense mechanisms. These findings highlight the potential of the curcuminoid 2102 as a promising candidate for the development of novel antifungal therapies, especially in the context of drug-resistant dermatophyte infections.
Despite the availability of potent antifungal compounds, invasive fungal diseases (IFD) are still a major cause for morbidity and mortality in immunocompromised pediatric and adult patients, and risk and outcome of IFDs are determined by the degree of the suppression of the specific arms of the immune system. This prompted us to review the current knowledge of immunotherapeutic antifungal approaches. We critically review important in vitro and animal data as well as clinical studies of immunotherapy for IFD, in particular granulocyte transfusion, the adoptive transfer of primary and genetically modified Natural Killer cells and fungal-specific T cells, and the use of colony-stimulating factors and cytokines. Although promising data of in vitro and animal models have been reported for many strategies, no clear benefit has been demonstrated in the clinical setting to date.
The review summarizes the existing literature on epidemiology, pathogenesis, the clinical spectrum, and manifestations, as well as diagnostic testing and treatment of coccidioidomycosis, and discusses the role of cutaneous manifestations in facilitating early diagnosis. The recent literature emphasizes a variety of clinical manifestations, confirms the added value of combining histopathology/serology, culture, and molecular tests to increase diagnosis accuracy, but also reinforces triazoles as the first-line therapy. Increasing evidence also highlights the host Th1 and Th17 immune response, as well as genomic virulence factors, as key drivers of disease heterogeneity. Early identification of cutaneous signs is crucial for effective treatment, limiting the spread of the disease, and improving outcomes. Severe or refractory disease often requires amphotericin B. Future research should focus on refining rapid diagnostics, risk prediction, and optimized antifungal regimens in both endemic and nonendemic settings. These priorities may guide prospective studies and standardized management pathways to enhance outcomes in diverse populations worldwide.
To review the current literature to understand and analyze the impact of climate change on the spatial dynamics of primary cutaneous coccidioidomycosis. Establishing a causal relationship between climate change and the incidence of primary cutaneous coccidioidomycosis is challenging due to the low number of reported cases. Strong evidence that climate change has altered the epidemiology of pulmonary coccidioidomycosis suggests the same impact on cutaneous infection. Global warming, climate migration, and extreme weather events have led to changes in the spatial dynamics of coccidioidomycosis, both in its pulmonary and primary cutaneous forms, despite being a rare clinical entity. Currently, primary cutaneous coccidioidomycosis should be considered in the differential diagnosis of unusual skin lesions that occur in people living in areas traditionally known to be endemic, as well as in those that are not.
This comprehensive review aims to clarify the association between the fundamentals of onychomycosis in the elderly, clinical manifestations, diagnosis and safe treatment options. A meticulous search of literature was conducted using PubMed, Google scholar, and Springer link databases. We were able to portray the association between advanced age, age-related nail manifestations, as well as, the correlation in the increase in onychomycosis prevalence, and therapeutic response, adverse events and special considerations in elderly patients. In conclusion, this review focuses on disease’s etiology, epidemiology, clinical features, therapeutic strategies, and especially drug-to-drug interactions, adverse events in elderly patients with onychomycosis.
To examine current evidence regarding the bidirectional communication within the gut–brain–skin axis, the impact of microbiome dysbiosis on immune regulation, and its contribution to the development of inflammatory dermatoses, particularly those linked to Malassezia species. Emerging research supports a dynamic interaction between the intestinal and cutaneous microbiome, demonstrating that alterations in gut microbial composition can influence systemic immune responses and skin inflammation. Dysbiosis has been associated with increased intestinal permeability, systemic inflammatory signaling, and exacerbation of dermatologic conditions such as acne, psoriasis, atopic dermatitis, alopecia areata, and Malassezia-associated disorders. Additionally, psychosocial stress and dietary factors have been shown to modulate this axis. The gut–brain–skin axis represents a complex regulatory network in which microbial homeostasis plays a central role in maintaining immune balance and skin health. Disruption of this equilibrium may contribute to inflammatory and Malassezia-associated skin diseases. A deeper understanding of these interactions may open new avenues for microbiome-targeted therapeutic strategies.
Onychomycosis is hard to eradicate because the nail unit limits transungual drug delivery. A recalcitrant phenotype involves compact subungual fungal masses (dermatophytoma or fungal conglomerate), reported with dermatophytes and non-dermatophyte molds. We systematically reviewed treatment outcomes, emphasizing debulking and combination therapy. Evidence is mainly case reports and small cohorts with heterogeneous diagnostics, regimens, and outcome definitions. Debulking was commonly used via chemical keratolysis (e.g., urea) and/or physical methods (e.g., debridement, curettage, drilling, partial avulsion). Debulking may improve response by reducing compact fungal burden and facilitating antifungal access. However, comparative studies with standardized definitions, mycologic confirmation, and meaningful endpoints are needed to define optimal debulking strategies and therapeutic combinations.
The aim of this review is to provide an in-depth overview of chromoblastomycosis, with emphasis on emerging management strategies and therapeutic options, and to underscore potential gaps in the literature and priorities for future research. Among the newer triazoles, posaconazole has demonstrated greatest therapeutic potential in the treatment of chromoblastomycosis, including for severe and refractory disease. Adjunctive immunomodulatory therapies such as glucan, imiquimod, and acitretin have shown potential as well. Several novel and repurposed agents also have potential activity against dematiaceous fungi, including tricyclazole, HIV peptidase inhibitors, 1,10‑phenanthroline‑5,6‑dione, and benzimidazoles. A recently proposed combination protocol with debulking, intralesional amphotericin B, and oral terbinafine (DAT protocol) achieved cure in all 16 included patients in a 2025 case series. While excisional surgery remains the preferred physical therapeutic modality, several reports have shown favorable results with both photodynamic and heat therapy. Chromoblastomycosis continues to pose a therapeutic challenge, requiring prolonged antifungal therapy often combined with physical therapeutic modalities. Improved access to diagnostics and early intervention remain essential to reducing global disease burden.
Fusariosis is a life-threatening opportunistic fungal infection, especially among immunocompromised individuals, with high mortality rates due to diagnostic delays and antifungal resistance. Despite the increasing global burden, management guidelines for this fatal fungal infection are not much available. This review outlines clinical features, diagnostic approaches, and current treatment options to support effective identification and intervention. This systematic review followed PRISMA guidelines to assess the clinical, microbiological, and antifungal characteristics of fusariosis using global literature. Electronic databases including PubMed, Scopus, and Google Scholar were searched from December 2024 to May 2025 using the MeSH terms. Randomized control trials, cohort, case reports, and surveillance data reporting laboratory-confirmed fusarium infections were included. Two reviewers independently screened and extracted data using a standardized template covering demographics, clinical features, species identification, antifungal susceptibility, and treatment outcomes. Quality assessment was performed using adapted critical appraisal tools for observational studies and case reports. Among 139 articles, over 2015 to 2025, 84 (60.4
Invasive fungal diseases (IFDs) represent a significant cause of morbidity and mortality in the pediatric population, particularly in neonates and immunocompromised children. This narrative review aims to summarize the clinical conditions associated with opportunistic IFDs in pediatrics and to provide an updated overview of the indications, drugs, and strategies for primary antifungal prophylaxis. While Candida and Aspergillus species remain the primary threats, emerging pathogens such as Candida auris and rare molds (e.g., Fusarium, Lomentospora, Scedosporium) are increasingly reported. Advances in neonatal care have solidified the role of fluconazole prophylaxis in very-low-birth-weight infants, while new data support the use of echinocandins (micafungin and caspofungin) in specific high-risk cohorts, such as neonates with C. auris exposure or pediatric acute myeloid leukemia. Furthermore, the emergence of small molecule targeted therapies and the increasing use of aggressive immunosuppression for autoimmune disorders present new, though less defined, risks for IFD. Primary antifungal prophylaxis is a cornerstone in the management of high-risk pediatric patients, including preterm neonates, children with specific primary immunodeficiencies (e.g., chronic granulomatous disease), and those undergoing intensive chemotherapy or hematopoietic stem cell transplantation. The selection of antifungal agents must account for age-related pharmacokinetics, potential drug-drug interactions, and local resistance patterns. Effective prevention requires an integrated approach combining pharmacological prophylaxis—often supported by therapeutic drug monitoring—with rigorous environmental controls and hand hygiene to mitigate the risk of fungal exposure.
To provide a concise, practice-oriented synthesis on Candida urinary tract infections: epidemiology and clinical significance of candiduria; when candiduria reflects colonization vs. infection; pharmacology of key antifungals focused on urinary and renal tissue penetration; the roles of source control and urologic intervention; and management in special scenarios (pre-urologic procedures, obstruction, devices, and impaired renal function). Fluconazole remains first-line therapy for susceptible isolates given excellent urinary and renal penetration. Echinocandins and lipid amphotericin B achieve low urinary concentrations and may be unreliable for treatment of cystitis, whereas amphotericin B deoxycholate and flucytosine attain therapeutic urinary concentrations (with nephrotoxicity and hematologic toxicity considerations). Novel agents such as rezafungin, fosmanogepix, oteseconazole, ibrexafungerp and encochleated amphotericin B show promising PK/tissue distribution but there are limited data defining their potential role in treating lower-tract disease. Intravesical or nephrostomy instillation of amphotericin B can produce short-term clearance in resistant or device-associated infections, yet relapse is common without addressing obstruction or removing/exchanging hardware. Pre-procedural candiduria may increase postoperative complications in selected populations; short-course targeted therapy is reasonable before intermediate-/high-risk genitourinary interventions. Renal impairment requires dose adjustment for fluconazole and flucytosine, avoidance of cyclodextrin-containing IV azoles, and preference for lipid amphotericin when a polyene is needed. The work up of candiduria should prioritize confirming infection, prompt source control (catheter/device management, relief of obstruction), and organism-directed therapy. Treat selectively: many asymptomatic cases resolve with device measures alone; symptomatic or high-risk situations are best treated with fluconazole when active, or amphotericin B deoxycholate or flucytosine for resistant species. Reserve local instillation for carefully chosen cases. Coordinated ID–urology care and procedure-specific planning reduce relapse and complications; key gaps include standardized instillation regimens and trials defining who benefits from antifungal therapy and the role of novel antifungals.
This review aims to provide an updated, comparative overview of endemic mycoses affecting pediatric populations: paracoccidioidomycosis, talaromycosis, and sporotrichosis. It seeks to address gaps in clinical recognition, diagnosis, treatment strategies, and outcomes in children, with a focus on geographic and immunological risk factors. Recent studies have highlighted shifts in the epidemiology of these infections due to environmental and demographic changes. Advances include improved molecular diagnostics such as PCR and metagenomic sequencing, safer antifungal therapies like amphotericin B colloidal dispersion, and novel approaches such as nanotechnology for PCM treatment. New data from large pediatric cohorts underscore the burden of these diseases and variations in clinical presentation and to explore prevention strategies like immunization. Early diagnosis and targeted antifungal therapy are critical to favorable outcomes in pediatric endemic mycoses. Continued research is essential to improve access to rapid diagnostics and safe treatments, especially in resource-limited endemic regions.
This review aims to highlight the emerging role of Candida parapsilosis as a causative agent of onychomycosis, emphasizing its clinical features, antifungal resistance patterns, and biofilm-associated virulence. It underscores the importance of accurate identification and susceptibility testing to guide effective treatment and improve patient outcomes. Recent studies increasingly recognize Candida parapsilosis as a true pathogen in onychomycosis rather than a contaminant. biofilm formation has been confirmed as a key virulence factor, contributing to chronic infection and decreased therapeutic response. These findings support the need for routine mycological confirmation and antifungal susceptibility testing to guide targeted therapy. Onychomycosis is a frequent nail plate infection, and although it is mainly caused by dermatophytes, yeasts from the genus Candida spp may be involved. Historically C.parapsilosis was considered a contaminating fungus, but has slowly emerged as an etiological agent for onychomycosis, both in immunocompetent and immunosuppressed patients. Its clinical presentation includes chronic paronychia, onycholysis, subungal hyperkeratosis as well as color changes in the nail plate. The precise identification is important due to the documented antifungal resistance of some strains, specially to azoles. The virulence factors such as biofilm formation contributes to the chronicity of the disease, and hinders treatment efficacy. Current evidence supports the need of epidemiological and fungal susceptibility studies that will allow to use effectively the required antifungal therapy, thus, improving patient´s outcome.
Subcutaneous phaeohyphomycosis (PHM) is a type of mycosis that occurs by implantation and is caused by melanized fungi. It usually crops up following traumatic inoculation of dematiaceous fungi from soil or vegetation; thus, certain occupational groups such as farmers and gardeners are affected more often. This review highlights the underestimation of the condition, usually impaired by misdiagnosis, emphasizing the need for clinician awareness, keen diagnostic judgement, and efficient laboratory support in order to make an accurate timely diagnosis. Although historically, PHM has been predominantly reported in immunocompetent hosts, there have been increasing reports of PHM in immunocompromised hosts as well, highlighting its emerging significance in these patients. The clinical manifestation of subcutaneous PHM is highly varied, including chronic nodules, cysts, verrucous plaques, or abscesses. Thus, confirmation of PHM cases often requires an interdepartmental approach, including histopathology, fungal culture, and molecular sequencing. Additionally, diagnostic accuracy may be enhanced by newer advanced methods such as matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS) and next-generation sequencing. Subcutaneous phaeohyphomycosis remains an underrecognized clinical entity due to its diverse clinical presentations and frequent misdiagnosis. Accurate diagnosis relies on a high index of clinical suspicion supported by appropriate laboratory investigations, including conventional and advanced diagnostic modalities. Management typically involves complete surgical excision, often supplemented by systemic antifungal therapy such as itraconazole, voriconazole, or posaconazole, underscoring the importance of early recognition and timely intervention for optimal outcomes.
We conducted a narrative review of the literature published between January 2021 and January 2026 using the PubMed and SciELO databases. The following search strategy was applied: (“sporotrichosis” OR “sporotrichoses”) AND (“Sporothrix schenckii” OR “Sporothrix globosa” OR “Sporothrix brasiliensis”) AND (comparison OR clinical OR treatment OR epidemiology OR virulence), with full-text articles available in English, Spanish, or Portuguese. This review addresses epidemiology, genotyping, immunology, routes of transmission, clinical manifestations in humans and animals, diagnostic approaches, treatment strategies, and measures for prevention and control. Advances have been reported recently across all topics addressed in this review. Increasing geographic spread of S. brasiliensis has been reported, along with the reports of new transmission routes, atypical clinical manifestations of the disease, novel diagnostic approaches, and emerging antifungal agents under pre-clinical investigation for treatment. This review shows that Sporothrix species differ significantly in transmission, virulence, and clinical outcomes, with S. brasiliensis being the most pathogenic due to its efficient zoonotic spread and association with severe disease. These findings highlight the importance of future studies from a One Health perspective.
This review synthesizes recent evidence on how the vaginal microbiota, especially Lactobacillus species, interacts with opportunistic yeasts of the genera Candida and Nakaseomyces to shape health and disease. It emphasizes the shift from the narrow term Candida vulvovaginitis to the more accurate and clinically meaningful concept of fungal vulvovaginitis. Recent evidence indicates that women presenting with vulvovaginitis exhibit a high prevalence of infectious etiologies, predominantly bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC), occurring either as isolated conditions or as mixed infections, with frequent BV fungal co-infection.Vaginal microbiota imbalances, including intermediate states and loss of dominant lactobacilli, markedly increase infection risk. Microbiome analyses identify Nakaseomyces glabratus as a key pathogen in recurrent fungal vulvovaginitis, linked to shifts in Firmicutes and higher Bifidobacterium. Emerging approaches, such as transplants or probiotics, can restore Lactobacillus dominance without promoting organisms associated with bacterial vaginosis or fungal vulvovaginitis. Fungal vulvovaginitis (FVV), primarily caused by Candida albicans and Nakaseomyces glabratus, is a prevalent gynecological infection associated with vaginal dysbiosis and excessive inflammatory responses. The loss of protective Lactobacillus species, particularly L. crispatus and L. iners, alters vaginal pH and immune balance, favoring fungal overgrowth and recurrence. Risk factors include antibiotic use, diabetes, pregnancy, and immunosuppression. C. albicans exhibits strong invasive capacity through morphogenesis and virulence factors such as adhesins and candidalysin, while N. glabratus persists through biofilm formation, stress resistance, and immune evasion. Conventional antifungal therapies often fail to prevent recurrence, prompting interest in alternative treatments such as vaginal microbiota transplantation (VMT), synthetic bacterial consortia transplantation (SBCT), and Lactobacillus-based probiotics. Restoring microbial equilibrium and regulating immune pathways, including IL-22 and IL-18, may enhance mucosal defense and reduce inflammation, providing a promising approach for managing recurrent fungal vulvovaginitis.
Fungal resistance is a major public health concern that reduces the efficacy of antifungal therapies and increases hospital mortality rates. This review aims to discuss how bioinformatics tools contribute to understanding resistance mechanisms and to the rational design of novel antifungal agents. Bioinformatics approaches such as genomic analysis, protein structural modeling, and multi-omics integration have advanced the comprehension of fungal pathogen biology. These methods facilitate the identification of molecular targets and the strategic design of antifungal drugs. In silico techniques, including molecular docking and molecular modeling, have shown great potential for discovering and optimizing antifungal and adjuvant molecules that enhance existing therapies. Nevertheless, the limited availability of experimental data, high computational costs, and difficulties in clinical validation remain major barriers to translating these findings into therapeutic applications. The integration of bioinformatics into antifungal research provides valuable insights into resistance mechanisms and drug development strategies. Despite current limitations, continuous investment in research and technological innovation is crucial to overcoming these challenges and broadening the antifungal therapeutic arsenal.
This review aims to synthesize current evidence on Neoscytalidium dimidiatum onychomycosis, an emerging non-dermatophyte infection that increasingly challenges diagnostic accuracy and therapeutic success. We seek to clarify its taxonomic characteristics, clinical presentation, epidemiology, and resistance patterns, addressing how clinicians can better identify and manage this difficult-to-treat pathogen. Neoscytalidium dimidiatum has increasingly been acknowledged as a cause of onychomycosis and superficial dermatomycoses, particularly in tropical and subtropical areas. Its dual synanamorphs and rapid growth yield darkly pigmented colonies and mixed hyaline dematiaceous hyphae. Clinically, it mimics dermatophyte onychomycosis but often shows gray-black discoloration, multinail involvement, and marked resistance to standard antifungals. Current evidence indicates that N. dimidiatum represents a growing global threat due to environmental exposure and inherent antifungal resistance. Accurate recognition, mycological confirmation, and tailored combination therapy are essential to improving outcomes.
The zoonotic nature of various dermatophytes poses a threat to both animals and humans. Increasing antibiotic resistance among several dermatophytes has raised the risk of treatment failure. The current review summarises the efficacy of biosurfactants as a green alternative to treat dermatophytosis. Although there are various reports about the antimicrobial activity of different biosurfactants, limited studies and reviews have been conducted on the usefulness of biosurfactants to treat dermatophytosis. Latest reports have unequivocally proved the antifungal efficacy of various biosurfactants against common dermatophytes. The current review discusses the findings of research works carried out globally in this aspect and highlights the market potential of biosurfactants as antidermatophytic agents. The present review focuses on the importance of biosurfactants as potential antifungal agents against dermatophytosis in humans and animals. It also emphasizes use of biosurfactants as a replacement to chemically synthesised antifungals for the treatment of dermatophytosis.
