Search Results (478)

Exophiala endophthalmitis of exogenous origin is an exceptionally rare but severe ocular infection, characterized by diagnostic delays, limited therapeutic guidance, and frequently poor outcomes. Herein, we report one new case of an 80-year-old woman who presented with severe fungal keratitis progressing to endophthalmitis two years after an uncomplicated cataract surgery. The condition was initially misdiagnosed and treated with topical antibiotics and corticosteroids. By cultivation, microscopy, histopathological, and PCR analysis of the samples, Exophiala dermatitidis was identified as the causative agent. Despite targeted antifungal therapy with voriconazole, the disease rapidly progressed, resulting in corneal perforation and evisceration of the affected eye. The number of confirmed cases of this infection remains very limited. To address this gap, we conducted a structured review of all reported instances of exogenous Exophiala endophthalmitis, in which Exophiala dermatitidis emerged as the predominant causative species. Common predisposing factors included corneal barrier disruption, ocular surgery, diabetes mellitus, and corticosteroid use. Diagnostic confirmation was frequently delayed, and treatment outcomes varied. Amphotericin B-based regimens were associated with poor results, whereas voriconazole, particularly when combined with surgical intervention, demonstrated more favorable outcomes. Exogenous Exophiala endophthalmitis remains underrecognized, with limited evidence to guide management. This entity should be considered in postoperative or trauma-associated intraocular inflammation, and current evidence supports azole-based therapy combined with surgical intervention when indicated. Full article

Digestive candidiasis is a major opportunistic infection among people living with HIV (PLHIV). In Gabon, data on antifungal resistance remain limited. This study aimed to characterise Candida colonisation and antifungal resistance according to anatomical site and species in Libreville. In this cross-sectional study, 108 PLHIV provided paired oral and stool samples. Candida spp. was identified using conventional phenotypic methods. Antifungal susceptibility to azoles and polyenes was assessed by disc diffusion following CLSI guidelines. Resistance burden was classified by drug class and by cumulative number of antifungal agents involved. Digestive colonisation was detected in 97 (89.8%) participants. Oral and intestinal colonisation rates were 78.7% and 66.7%, respectively, with dual-site involvement in 55.6%. Among resistant isolates, Candida albicans accounted for 55.2% (oral) and 48.9% (intestinal), while non-albicans Candida represented 29.8% and 44.4%, respectively. Multidrug resistance was significantly higher in intestinal than oral isolates (36.2% vs. 11.8%; OR = 4.99; 95% CI: 2.04–12.16; p < 0.01). Resistance was predominantly azole-driven, with complex cumulative resistance profiles in intestinal isolates. The intestinal tract showed resistance profiles consistent with a preferential accumulation of MDR Candida populations in PLHIV. Site-specific resistance patterns underscore the importance of targeted sampling and antifungal stewardship strategies in resource-limited settings. 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/Objectives: The increasing resistance of Candida species to conventional antifungals, particularly azoles, poses a critical public health challenge due to high mortality rates associated with candidemia. This study aimed to describe the chemical composition of the essential oil from Haplopappus foliosus (EO-BAI) and evaluate its antifungal properties, along with its nanoemulsion (NE-BAI) and major constituents, against a panel of clinical Candida isolates. Methods: EO-BAI was extracted via steam distillation and analyzed using GC-MS. A nanoemulsion was synthesized through ultrasonic emulsification and characterized by DLS and microscopy (SEM/STEM). Antifungal activity (MIC/MFC) was determined following CLSI M27-A3 guidelines. Time–kill kinetic studies were conducted on C. albicans, and an in silico approach was used to describe interactions with Als9-2 and CYP51 targets. Results: The EO-BAI profile was dominated by terpinen-4-ol (27.27%) and α-bisabolol (10.40%). The NE-BAI exhibited a droplet size of approximately 22 nm with an encapsulation efficiency of 88.72%. Among the tested samples, α-bisabolol emerged as the core bioactive driver (MIC = 16 µg/mL against C. albicans). While NE-BAI showed reduced initial activity at 24 h, it demonstrated enhanced efficacy by 48 h, matching fluconazole’s potency and maintaining a definitive fungicidal effect. Docking analysis confirmed that α-bisabolol establishes stabilizing interactions with key virulence and membrane homeostasis targets. Conclusions: The NE-BAI provides a sustained delivery of its bioactive terpenes, preserving their fungicidal nature and positioning them as robust therapeutic alternatives to conventional treatments. Full article

Candida albicans is a common opportunistic pathogen. Long-term use of azole antifungals faces challenges like resistance, necessitating novel agents. Tea tree oil (TTO), a natural broad-spectrum antimicrobial, shows promise, but its molecular mechanisms, particularly concerning novel cell death pathways, require clarification. This study comprehensively evaluated the antifungal mechanism of TTO against C. albicans using transcriptomics. Antifungal susceptibility assays were conducted to assess the effects of TTO and its components (4-terpineol, terpenes, and γ-pinene) on the growth of C. albicans hyphae and biofilms. Fluorescent labeling and biochemical analysis were employed to detect ferroptosis markers. Transcriptomic results indicate that TTO induces 423 differentially expressed genes and systematically inhibits the development of C. albicans hyphae through mechanisms such as oxidative stress, iron homeostasis disruption, disruption of cell wall integrity, and interference with ergosterol metabolism. Notably, the significant enrichment of redox enzyme activity and iron ion binding functions, along with changes in the glutathione metabolic pathway, suggest that ferroptosis may be involved in this process. Subsequent studies revealed that the compound 4-pinene most effectively inhibits the pathogenicity of C. albicans by suppressing its adhesion, hyphae formation, and biofilm formation, whereas terpinene induces the accumulation of reactive oxygen species (ROS) and increases lipid peroxidation in C. albicans; furthermore, following treatment with an iron-mediated apoptosis inhibitor, terpinene enhances the viability of the treated C. albicans cells. Full article

Background: Antifungal resistance among Candida species represents a growing clinical challenge, particularly in the context of increasing prevalence of non-albicans species. Methods: We conducted a retrospective analysis of 747 fungal isolates collected between 2021 and 2026, evaluating species distribution, antifungal susceptibility profiles, minimum inhibitory concentration (MIC) patterns, and temporal trends in resistance. Results: Non-albicans Candida species accounted for 67.5% of isolates, exceeding the proportion of Candida albicans. Fluconazole and flucytosine exhibited the highest resistance rates (16.1% and 17.4%, respectively), while amphotericin B showed the highest susceptibility rate (82.1%). MIC analysis revealed elevated MIC90 values for azoles in Candida glabrata and Candida krusei, consistent with reduced susceptibility. A significant association between antifungal agent and susceptibility profile was observed (χ² = 33.81, p < 0.001; Cramér’s V = 0.205). Temporal analysis demonstrated fluctuating resistance patterns rather than a consistent increase over time. Multidrug resistance was uncommon (2.5%), although non-susceptibility to multiple agents was more frequent (20.3%). Conclusions: The study highlights substantial variability in antifungal susceptibility across Candida species and antifungal agents, emphasizing the importance of continuous surveillance and species-specific treatment strategies. Full article

Vulvovaginal candidiasis (VVC) is a common gynecological infection, with Pichia kudriavzevii emerging as a significant pathogen due to its intrinsic fluconazole resistance and biofilm-forming capacity. This study investigates the antifungal efficacy and mechanisms of tannic acid (TA) against P. kudriavzevii, as well as its potential to reverse azole resistance across multiple Candida species with distinct resistance profiles. TA significantly inhibited P. kudriavzevii growth, surface colonization, and virulence gene expression at 3 μg/mL. Mechanistically, TA protected the human vaginal epithelial cell line VK2/E6E7 by reducing ROS levels, restoring mitochondrial membrane potential, and suppressing IL-1β and IL-18 release through modulation of the NLRP3-Caspase1-ASC axis. Furthermore, TA demonstrated synergistic activity when combined with azoles against five clinically azole-resistant Candida isolates spanning three Candida species with distinct resistance mechanisms: P. kudriavzevii (intrinsic), C. albicans (acquired), and N. glabrata (FKS-mediated). This study highlights TA as a promising natural therapeutic agent for P. kudriavzevii infections and offers a novel strategy for combating multidrug-resistant Candida through combination therapy. Full article

Aspergillus fumigatus is a leading cause of invasive fungal disease in humans and is classified as a critical priority threat by the World Health Organization. Triazole antifungals remain the cornerstone of therapy, yet their effectiveness is steadily being eroded by the continuous rise in drug resistance. Most resistance mechanisms trace back to mutations in Cyp51A, spawning well-defined genotypes such as TR₃₄/L98H and TR₄₆/Y121F/T289A. However, the Cyp51A genotype–phenotype landscape in A. fumigatus is far from straightforward. Isolates that share an identical TR genotype can display strikingly divergent susceptibility profiles, and mutational hotspots in Cyp51A, such as G54, M220 and G448, are linked to varying resistances, challenging assumptions about predictable resistance behavior. Complicating matters further, an expanding array of resistance mechanisms, independent of Cyp51A, is now being uncovered. This review summarizes the current state of knowledge on azole resistance in A. fumigatus, dissecting the intricate genotype–phenotype relationships, spotlighting emerging non-Cyp51A pathways and outlining future strategies to enhance the detection and clinical management of antifungal resistance. Full article

Breakthrough invasive fungal infections (bIFIs) are a challenging serious complication in high-risk hematologic patients and allogeneic hematopoietic stem cell transplantation recipients that may negatively impact their outcome. Despite advances in antifungal prophylaxis, diagnostics, and supportive care, bIFI occurrence reflects a complex interaction between host immunosuppression, emergence of resistant pathogens and pharmacological variables, including subtherapeutic drug exposure. Candida spp. have shifted towards non-albicans yeasts, whereas breakthrough mold infections more frequently involve non-fumigatus Aspergillus, Mucorales, Fusarium spp., and Scedosporium/Lomentospora spp. Early clinical recognition, rapid therapy escalation, aggressive diagnostic investigation, a switch to liposomal amphotericin B-based regimens in patients on azole prophylaxis, and therapeutic drug monitoring are essential to improve outcomes. Reducing the growing global burden of bIFIs will also require improved access to high-quality diagnostics and strengthened educational and stewardship efforts that prioritize antifungal resistance as an urgent health concern. Full article

Itraconazole is the recommended first-line antifungal agent in blastomycosis treatment. However, pharmacokinetic limitations and adverse drug events may necessitate the use of alternative antifungal agents. The primary objective of the study was to retrospectively describe a cohort of patients with blastomycosis who received voriconazole (as partial or complete therapy), for complete or partial treatment, compared to those who received itraconazole alone. Secondary objectives included rationale for voriconazole selection, treatment response, mortality, and adverse drug events. This retrospective multicenter cohort study included adult patients with proven/probable blastomycosis who received itraconazole or voriconazole. Treatment response was evaluated at one year or end of therapy, whichever came first. Mortality outcomes were assessed within 7 days of the last documented azole dose. Propensity score weighting and subgroup analysis were utilized to control confounding variables between cohorts. A total of 119 patients receiving itraconazole and 25 receiving voriconazole as complete or partial treatment were included. Voriconazole was often selected for CNS involvement or after intolerance to alternative azoles. After propensity score weighting, no significant difference in complete or partial treatment response was observed. Rates of all-cause mortality and blastomycosis-related mortality were numerically higher in the voriconazole cohort. Adverse drug event rates were similar between cohorts; however, discontinuation due to adverse events was more common in the voriconazole cohort. Voriconazole was most utilized for the treatment of blastomycosis in cases with CNS involvement or intolerance to other azoles. A statistically significant difference in response rate was not identified between voriconazole-containing or itraconazole-treated patients; however, given limited sample sizes, further data is needed to assess the equivalency of these agents in the treatment of blastomycosis. Full article

Candida dubliniensis is an opportunistic yeast closely related to Candida albicans and an uncommon cause of central nervous system (CNS) infection. While isolates are often susceptible to azoles, reduced susceptibility or acquired resistance may occur, making species identification and antifungal susceptibility testing clinically relevant. We report a 3-year-old boy with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (ALL) in hematologic remission who developed chronic meningitis during maintenance chemotherapy. The initial presentation was non-specific (marked somnolence without fever or meningeal signs) and lumbar puncture performed to exclude CNS relapse revealed neutrophil-predominant pleocytosis and elevated protein; the cerebrospinal fluid (CSF) culture grew C. dubliniensis. Treatment with intravenous liposomal amphotericin B followed by prolonged fluconazole led to clinical improvement and sterile CSF. Six months later, progressive gait disturbance, limb pain, and episodic severe headaches recurred; repeat CSF cultures again yielded C. dubliniensis, with a changed susceptibility profile. Spine MRI demonstrated leptomeningeal enhancement involving the cauda equina nerve roots. Intravenous voriconazole with therapeutic drug monitoring was initiated and combined with intrathecal liposomal amphotericin B (seven doses, dose-escalated up to 3 mg), which was well tolerated and associated with rapid neurologic improvement, CSF sterilization, and radiologic resolution. At 12 months of follow-up, the patient remained infection-free and in leukemia remission. This case highlights that C. dubliniensis chronic meningitis may present subtly yet progress, requiring repeated CSF cultures with susceptibility testing; intrathecal liposomal amphotericin B can be a safe and effective adjunct to systemic therapy in refractory or recurrent disease. Full article

Oral fungal infections resulting from non-albicans Candida species and new opportunistic yeasts are increasingly linked to antifungal resistance, especially in individuals with periodontal disease. Bioactive compounds may serve as potential alternatives; nevertheless, there is a paucity of research that has comprehensively assessed their antifungal and antibiofilm efficacy against clinically defined oral yeast isolates. This study aimed to (i) describe the variety and antifungal resistance profiles of oral yeasts isolated from women with various periodontal diseases; (ii) assess four ethanolic extracts of Aseer medicinal plants (Foeniculum vulgare, Solanum incanum, Forsskaolea tenacissima, and Abutilon pannosum) for their antifungal and antibiofilm properties; and (iii) correlate phytochemical composition determined by GC–MS with biological activity. Oral samples (saliva and subgingival plaque) were collected from 50 female participants with documented periodontal parameters. Fungal isolates were identified using morphological, biochemical (VITEK 2), and molecular (ITS rDNA sequencing) methods. Testing for antifungal susceptibility was performed according to CLSI guidelines. Plant extracts were evaluated for antifungal activity (disk diffusion, MIC, MFC), antibiofilm activity (crystal violet assay and light microscopy), and phytochemical profiling (GC–MS). Fungal growth was detected in 37 of 50 samples (74%), yielding six yeast species: Nakaseomyces glabratus (40.5%), Candida tropicalis (18.9%), C. parapsilosis (13.5%), Pichia kudriavzevii (10.8%), Rhodotorula mucilaginosa (8.1%), and Aureobasidium melanogenum (8.1%). N. glabratus demonstrated reduced susceptibility to fluconazole. A. pannosum and F. vulgare exhibited the strongest in vitro antifungal activity (inhibition zones up to 19.2 mm; MIC 0.19–0.78 mg/mL; MFC 0.39–1.56 mg/mL), significantly greater than F. tenacissima (p < 0.0001). Sub-MIC concentrations of A. pannosum reduced C. tropicalis biofilm biomass by 59.6%. GC–MS analysis identified methyl salicylate (20.3–40.2%) and cyclohexanol derivatives (8.0–23.2%) as major constituents. Antifungal activity showed a trend in relation to methyl salicylate content (R² = 0.78). However, because only four plant extracts were included, this relationship should be interpreted as a descriptive observation rather than a statistically testable association. Ethanolic extracts of Abutilon pannosum and Foeniculum vulgare demonstrated significant in vitro antifungal and antibiofilm activity against clinically relevant oral yeasts, including azole-tolerant Nakaseomyces glabratus. The observed trends between phytochemical composition and biological activity warrant further investigation into their potential as adjunct therapeutic agents for oral fungal infections. Further studies are required to confirm these results and see if they can be used in therapeutic settings. Full article

Candida albicans is currently considered one of the most significant fungal pathogens in cetaceans and pinnipeds and the spread of antifungal-resistant strains pose significant threats to animal health and One Health concerns. Although C. albicans is the most commonly detected species, non-albicans Candida (NAC) species, including C. tropicalis, C. parapsilosis and Nakaseomyces glabratus and the multidrug-resistant C. auris, have been recognized in captive dolphins. This review examines the clinical patterns observed in marine mammal taxa: cetaceans are most commonly vulnerable to respiratory and disseminated mycoses owing to their distinct anatomical characteristics, whereas mucocutaneous infections are the common manifestation in pinnipeds. Localized mucocutaneous infections may progress to fatal systemic disease, with mortality rates approaching 100% in severe cases, despite therapeutic treatment. The most important predisposing factors are immunosuppression, long-term antibiotic treatment, environmental stress factors, and the deterioration of water quality. Diagnostic methods are based on cytology, histopathology, culture, and molecular methods, and treatment is mostly composed of systemic azole antifungals although with high levels of therapeutic failure. Recent results showed that there are high levels of azole resistance in the isolates of marine mammals that had no history of exposure to antifungal agents, which points to the role of aquatic environments as sources of resistance genes. The lack of knowledge remains particularly evident in species-specific pharmacokinetics and the development of evidence-based treatment guidelines. These infections also have broader implications for ecosystem health surveillance and the protection of endangered marine mammal populations. The current review highlights the One Health approach with marine mammals being at the core of ocean health surveillance and identifies the potential for zoonotic transmission. Full article

Superficial mycoses (dermatomycoses) are a growing healthcare concern due to antifungal resistance, particularly among aging and immunocompromised populations. Multiple efforts are underway to develop novel antifungals, including discovering new compounds with known or new mechanisms of action, extending indications or repurposing existing medications, and utilizing vaccination and nanotechnology platforms. Herein, we conducted a scoping review of novel antifungals for the treatment of dermatomycoses. An electronic literature search restricted to the past 10 years was performed in January 2026 using PubMed and Embase (Ovid). Olorofim and ME1111 represent novel drug classes that target intracellular metabolism. New agents belonging to the azole class demonstrate reduced drug–drug interactions (oteseconazole), a broader antifungal spectrum (voriconazole), and reduced pharmacokinetic complexity (fosravuconazole, super-bioavailable itraconazole). Other investigational compounds include allicin, a phytocompound, and miltefosine, a repurposed antileishmanial drug. Based on our current understanding of dermatophyte immunity, antimicrobial peptides and vaccines targeting virulence factors (e.g., subtilisins) represent novel strategies. Nanotechnology platforms also show promise in introducing new antifungal agents (e.g., metal nanoparticles, nitric oxide-releasing nanoparticles), as well as developing topical formulations to enhance the bioavailability and safety profiles of existing antifungals (amphotericin B, ketoconazole, voriconazole). Full article

Candidozyma auris is an emerging opportunistic fungal pathogen that can cause serious catheter-related blood stream infections associated with high morbidity and mortality. The traditional antifungal treatment with polyenes, azoles or echinocandins is becoming less effective due to both intrinsic and developed resistance, complicating treatment. This study demonstrates the potent fungicidal activity of carboxyl-functionalized graphene quantum dots (cGQDs) against a panel of C. auris strains, spanning clades I to V, and a Candida albicans reference strain. Photoactivation of cGQDs in suspension with 435 nm blue light killed 99.9% of the fungi within 30 min even though the majority of test strains were resistant to at least one conventional antifungal. Moreover, cGQDs coated on flexible polydimethylsiloxane surfaces and commercial catheters via electrostatic layer-by-layer deposition with alternating positively charged polydiallyldimethylammonium polymer showed strong fungicidal activity against C. auris and C. albicans. These findings show that the cGQDs, both in suspension and in a thin film coating, have potential for future clinical development. In particular, their application to catheters may help prevent Candidozyma and Candida catheter-related infections. Full article