Vulvovaginal candidiasis (VVC) is a frequent contributor to vulvovaginal symptoms; however, its clinical features are similar to those of bacterial vaginosis, trichomoniasis, mixed vaginitis, and non-infectious vulvovaginal disorders. Current laboratory approaches for vulvovaginal candidiasis are examined in terms of diagnostic accuracy, species determination, antifungal susceptibility testing, and clinical use. Evidence was synthesized from microscopy, potassium hydroxide preparation, culture techniques, species-distribution studies, molecular diagnostic assays, multiplex panels for vaginitis, susceptibility studies, and implementation research. Microscopy offers rapid and inexpensive evaluation but has limited sensitivity, particularly in low-burden infections and diseases caused by non-albicans Candida species. Culture still plays an important role in organism recovery, species identification, detection of mixed infections, and determination of antifungal susceptibility; however, its interpretation is limited by delayed turnaround time, sampling conditions, previous antifungal exposure, and the inability to distinguish colonization from infection. In non-albicans disease and recurrent, persistent, or refractory infections, antifungal susceptibility testing is most helpful. Species-level identification is becoming increasingly relevant, given the differences in epidemiology, recurrence, and antifungal response among Candida species. Molecular assays provide higher sensitivity, more rapid turnaround, and detection of co-infections. However, highly sensitive assays can lead to the detection of asymptomatic colonization and potential overtreatment when laboratory findings are not correlated with clinical presentation. A tiered laboratory workflow combining symptom assessment, microscopy, culture, species identification, selective molecular testing, and targeted susceptibility testing is the most clinically informative and provides complementary information to support patient management.
With the expansion of new targeted and immune-based therapies, there is increased uncertainty regarding Pneumocystis jirovecii pneumonia (PJP) risk and use of prophylaxis. Bispecific antibodies, chimeric antigen receptor (CAR)-T cell therapy, B-cell lymphoma-2 (BCL-2) inhibitors and Bruton tyrosine kinase (BTK) inhibitors cause distinct immune deficits. Determining PJP risk in patients treated with these agents is important to inform evidence-based prophylaxis strategies. PJP risk is infrequently and incompletely described in early clinical trials of novel therapies for haematological malignancies. Although observational studies and case series highlight the need for ongoing surveillance and consistent reporting of prophylaxis use and PJP events, it is essential to define treatment-associated risk and inform the role of routine PJP prophylaxis in clinical practice. Current guidelines are based on limited evidence and inconsistencies in guideline recommendations further contribute to variability in prophylaxis practices. Despite the rapid increase in clinical exposures to bispecific antibodies, CAR-T cell therapies, BCL-2 inhibitors and BTK inhibitors, the magnitude and timing of PJP risk remains uncertain. PJP risk is high in recipients of CAR-T cell therapy, for whom routine prophylaxis is recommended; moderate and frequently reported in recipients of bispecific antibodies; and low to variable in recipients of BTK and BCL-2 inhibitors, respectively, for whom prophylaxis is generally reserved for those with additional risk factors. Prospective studies with standardised PJP surveillance and prophylaxis reporting are required to define high-risk populations and periods of vulnerability, enabling risk-stratification prophylaxis recommendations that balance PJP prevention against toxicity and treatment burden.
To review and analyze case reports of dermatophytosis caused by species of the T. mentagrophytes complex during the 2020–2026 period to understand the current clinical and mycological characteristics of these fungal infections. Dermatophytosis caused by the T. mentagrophytes complex is characterized by a variable response to antifungal agents, atypical lesions, novel transmission routes, and difficulties in differentiating species within the complex, therefore, a molecular approach is required to accurate species identification. This situation forces dermatologists to adopt new strategies to achieve a specific diagnosis that leads to effective antifungal treatment and the establishment of appropriate prevention or control measures. There has been an increase in reported cases of dermatophytosis caused by the T. mentagrophytes complex, which could reveal an emerging public health problem that requires attention due to the variable response to antifungal agents, the extensive and severe lesions, and sexual transmission. Dermatologists should adopt new strategies focused on the use of phenotypic and molecular tests, combined with a thorough medical history and patient anamnesis, to achieve a specific diagnosis and effective antifungal treatment, as well as the establishment of prevention and control measures.
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.
