A Th2-favored phenotype can predispose individuals to symptomatic and disseminated coccidioidomycosis. Dupilumab, which impedes Th2 immunity, is sometimes used adjunctively for disseminated coccidioidomycosis. To determine whether dupilumab alters the clinical course of coccidioidomycosis, we retrospectively reviewed records of 1,561 patients who received dupilumab; 42 had coccidioidomycosis diagnosed from October 6, 2018, through July 16, 2025 (Mayo Clinic [Phoenix, Arizona]). Eleven patients received dupilumab before having symptomatic coccidioidomycosis, and 3 received dupilumab before asymptomatic coccidioidomycosis was identified. Twenty-eight patients received dupilumab after coccidioidomycosis was diagnosed: 16 were asymptomatic and seropositive, without reactivation on dupilumab, and 12 had ongoing symptoms (most eventually resolved). No patients had adjunctive dupilumab treatment. Three patients had disseminated coccidioidomycosis: 2 initiated dupilumab after coccidioidomycosis was diagnosed and 1 before, and each eventually had symptomatic improvement. We did not observe patterns of coccidioidomycosis worsening after dupilumab initiation or an increased prevalence of coccidioidomycosis among patients already receiving dupilumab.
This study aimed to evaluate the diagnostic efficacy of calcofluor white (CFW) staining for sporotrichosis using archival formalin-fixed paraffin-embedded (FFPE) specimens, compared with conventional histochemical stains. A total of 75 FFPE specimens collected between 2010 and 2023 from patients with culture- or sequencing-confirmed sporotrichosis cases were enrolled, with 70 specimens from non-fungal infection cases using as controls. Serial tissue sections were stained with CFW, periodic acid-Schiff (PAS), and Gomori methenamine silver (GMS) staining, respectively. The detection rates, diagnostic accuracy metrics, and storage duration effects were assessed. CFW staining yielded a fungal detection rate of 78.6
Candida bloodstream infections remain a significant complication of malignancies and their therapies. To investigate the epidemiology of Candida species causing bloodstream infections in patients with malignancies. We retrospectively reviewed bloodstream infections due to Candida from July 2008 to June 2023 in patients admitted under hematological, solid tumor and surgical services. Common species included C. albicans, Nakaseomyces glabratus (formerly C. glabrata), Pichia kudriavzevii (formerly C. krusei), C. parapsilosis complex and C. tropicalis. The rest were classified as uncommon. Incidence of candidemia was 0.46 episodes per 1,000 patients-days of admission. Of 265 episodes of candidemia, 102 (38.5
To describe the first neonatal invasive Candida auris infection in Brazil and its successful clinical and infection control management. Retrospective description of the clinical course, microbiological findings, antifungal susceptibility evolution, and follow-up of an extremely preterm infant. A 25 + 4-week male neonate developed bloodstream and urinary C. auris infection during the first week of life. Progressive amphotericin B resistance in urine isolates required the addition of fluconazole. No secondary NICU cases occurred. Early diagnosis, serial susceptibility testing, and immediate containment measures enabled successful treatment and prevented nosocomial spread.
Candida parapsilosis sensu stricto has emerged as a major cause of healthcare-associated candidemia, with increasing reports of fluconazole resistance worldwide. This resistance is most commonly associated with amino acid substitutions in Erg11p, particularly Y132F; however, regional variation in resistance mechanisms and clonal dissemination remains not fully understood. This study investigated the molecular epidemiology and genomic landscape of fluconazole-resistant C. parapsilosis in Paraná, Southern Brazil, over a 10-year period. A total of 54 resistant isolates identified between 2014 and 2024 were retrospectively analyzed; 51 viable isolates were confirmed by species identification, antifungal susceptibility testing, and microsatellite genotyping. A subset of 18 representative isolates underwent whole-genome sequencing for phylogenomic analysis. Variants in genes associated with azole resistance, including ERG11, MRR1, TAC1, CDR1, MDR1, ERG3, and ERG6, were characterized. Fluconazole resistance emerged in 2018 and increased thereafter. Phylogenomic analysis revealed two geographically structured lineages: a dominant clone circulating across multiple healthcare institutions in the Curitiba metropolitan area and a second lineage restricted to the northern region of the state. The dominant clone showed minimal genomic diversity (0–5 SNPs), consistent with long-term persistence. A conserved resistance profile was observed, with 17 of 18 sequenced isolates harboring the K143R substitution in Erg11p, while all retained the wild-type residue at position 132. The single isolate lacking ERG11 mutations carried a novel C849Y substitution in the Mrr1p regulator. These findings demonstrate the emergence and persistence of a highly clonal fluconazole-resistant C. parapsilosis lineage in Southern Brazil, characterized by a conserved K143R substitution independent of Y132F. The detection of closely related isolates across different hospitals underscores the need for regional genomic surveillance of hospital-adapted fungal pathogens.
Invasive fungal infections (IFIs) cause significant morbidity and mortality in immunocompromised pediatric patients; systematic data comparing mold- and yeast-related infections remain limited. To evaluate epidemiology, clinical features, antifungal treatment, and outcomes of proven infectious fungal infections (IFIs) in immunocompromised children, comparing mold and yeast infections. This single-center retrospective study included 65 immunocompromised patients aged ≤ 18 years with proven IFIs diagnosed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) criteria. Of 65 patients (75.4
Candidemia poses a life-threatening complication for immunocompromised patients, including those undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Non-albicans Candida species are increasingly recognized as causative pathogens in this population, with azole resistance having emerged as a global concern. Candida orthopsilosis, a member of the Candida parapsilosis species complex, is generally considered susceptible to azole antifungal agents. Although sporadic reports of azole-resistant isolates have surfaced worldwide, no such cases have been documented in Japan. Furthermore, genetic evaluations of azole-resistant C. orthopsilosis have primarily been conducted in Europe. We present the first case of fluconazole-resistant C. orthopsilosis bloodstream infection in a 73-year-old man following allo-HSCT for acute myeloid leukemia in Japan. Whole-genome sequencing identified an ERG11 G458S substitution, a known mechanism of fluconazole resistance in C. orthopsilosis, representing the first identification of this mutation outside Europe. Our findings highlight the importance of continued surveillance of antifungal resistance in C. orthopsilosis.
Candida albicans is a major opportunistic fungal pathogen causing various mucosal infections, including oral candidiasis, poses challenges in current antifungal therapy because of limited number of drugs, increased pathogen resistance, and notable toxicity associated with existing medications. Combination therapy is crucial for optimizing treatment outcomes. In this study, cepharanthine (CEP) was explored as an adjunct to amphotericin B (AmB) to elucidate the potential mechanism of action of drug combinations against Candida albicans. The minimum inhibitory concentration (MIC) was determined using the checkerboard method, and the fractional inhibitory concentration index (FICI) was computed. The combination of cepharanthine and amphotericin B had a synergistic effect (FICI < 0.5) on both standard strains and 73 clinical strains of Candida albicans, leading to significant inhibition of metabolism, hyphal growth, and biofilm formation. Transcriptome sequencing, membrane permeability studies, assessment of mitochondrial membrane potential, and scanning electron microscopy revealed that cepharanthine primarily targeted the membrane structure of Candida albicans. RT‒qPCR analysis demonstrated that cepharanthine in combination with amphotericin B suppressed sphingolipid synthesis by downregulating the expression of the plasma membrane-associated gene PMP3, thereby compromising cell membrane integrity. Molecular docking model analysis further supported the binding affinity of both drugs to the PMP3 protein. The combined use of cepharanthine and amphotericin B presents a promising approach for the clinical management of oral candidiasis.
The existing predictive models for talaromycosis in people living with HIV without skin lesions are limited by established risk factors and traditional statistical approaches. This study aims to develop an interpretable machine learning(ML) model for predicting the presence of talaromycosis in HIV patients without skin lesions and to validate its clinical applicability. This retrospective multicenter study involved the analysis of electronic medical records from four tertiary hospitals in China, covering the period from 2010 to 2019. The training dataset comprised 1009 HIV patients with opportunistic infections, while external validation was conducted using data from 305 patients at an independent center. From an initial set of 36 variables, twelve key features were selected, including albumin, absolute lymphocyte count, hemoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, C-reactive protein, white blood cell count, platelet count, peripheral or abdominal lymphadenopathy, CD4+ T-cell count, and age. Five ML algorithms were evaluated using tenfold cross-validation. Model performance was measured using the AUC, ACC, and F1-score. Calibration curves and decision curve analysis (DCA) were employed to assess the model’s reliability and clinical net benefit. The optimal model was subsequently implemented as a web-based tool. The Support Vector Machine (SVM) exhibited superior performance compared to other models, achieving an AUC of 0.809 (95
Candidozyma auris (syn. Candida auris) is an emerging multidrug-resistant yeast of growing clinical and environmental concern. Despite its increasing detection in healthcare settings worldwide, environmental evidence remains scarce. This study presents the first molecular detection of C. auris DNA in surface waters of Türkiye, within the Ramsar-protected Gediz Delta, as part of the national One Health Surveillance Framework. A total of 80 surface-water samples were collected from five wetland ecosystems Tuz Lake, Kulu Lake, Göksu Delta (Akgöl and Paradeniz Lagoons), Kızılırmak Delta, and Gediz Delta. Physicochemical parameters; temperature, pH, and salinity were recorded in situ using a multi parameter sensor. Environmental DNA was extracted from 2 L of 0.22 µm Sterivex-filtered water and analyzed via qPCR using C. auris-specific (CauF/CauR) and Candida-genus (CauRelF/CauRelR) primer sets. Yeast isolation was performed on CHROMagar™ Candida Plus, and identification was achieved by MALDI-TOF MS. C. auris DNA was detected in one sample (1.25
Blastomycosis is an invasive dimorphic fungal infection capable of causing severe disseminated disease in immunocompromised hosts. Although traditionally endemic to North America, increasing molecular evidence suggests a broader geographic distribution. Iran is not considered endemic, and no prior species-level confirmed cases of Blastomyces percursus have been reported. We report a 31-year-old liver transplant recipient who developed progressive diffuse papulopustular and verrucous necrotic cutaneous lesions 17 months after transplantation. Initial diagnostic evaluation was inconclusive. Detection of fungal DNA consistent with Aspergillus species in skin biopsy specimens prompted initiation of voriconazole therapy; however, the clinical course progressed despite treatment. The patient subsequently developed severe weight loss, high-level cytomegalovirus (CMV) viremia, pulmonary nodules, and mucosal involvement. Initial fungal culture suggested Pseudallescheria boydii, but re-evaluation at a reference mycology laboratory raised suspicion for blastomycosis. Definitive species identification was achieved by amplification and Sanger sequencing of the internal transcribed spacer (ITS1–5.8S–ITS2) region. The 520-bp sequence demonstrated 99.6–100
Candidozyma auris (formerly Candida auris) is an emerging yeast that causes bloodstream infections, especially in immunocompromised patients, and presents high resistance and virulence rates. To date, six clades have been established worldwide and the number of outbreaks caused by this microorganism has been increasing every year, causing concern in the medical community. Therefore, this study investigated the heterogeneity among clades of C. auris by evaluating the virulence profile and mechanism of infection using an in vivo model of Galleria mellonella. G. mellonella was infected with different clades (I, II, III and IV) of C. auris, C. albicans ATCC 5341 and C. parapsilosis ATCC 22019 for virulence and histopathologic evaluation. Aggregative strains of C. auris InP13 (I) and VEN C6 (IV) had a greater rate of melanization and larval mortality among the C. auris isolates, therefore, being the most aggressive strains. C. albicans caused the most melanization among all strains at the highest inoculum concentration (106 cells/mL). Histopathologic examination showed a greater number of granulomas in the lower and upper extremities of G. mellonella. The granulomas ranged from 0.07–0.11 nm in diameter. All strains showed biofilms adhering to larval tissue, which was more evident for InP13, VEN C6 and C. albicans. Infiltration of tissues by yeasts, pseudohyphae and chlamydospores (a resistance structure formed by C. albicans in stress environments) morphotypes were observed. The aggregative strains were more virulent and had a greater ability to form biofilms and granulomas, showing heterogeneity among the different C. auris clades.
Candidemia is a life-threatening invasive fungal infection, particularly in patients admitted to intensive care units (ICUs). Epidemiology of candidemia and antifungal resistance have been significantly affected in COVID-19 pandemic. We analysed candidemia cases in neonatal, paediatric, and adult ICUs at Hippokration General Hospital in Thessaloniki, Greece (site 1) and Kayseri City Training and Research Hospital in Kayseri, Türkiye (site 2) from January 2020 to December 2023. Epidemiology, species distribution, and antifungal susceptibility of cases were compared. A total of 388 patients from site 1 and 379 patients from site 2 were included. A significant increase in the incidence of candidemia was observed in both hospitals during the COVID-19 pandemic. Candida parapsilosis was the most common species in all ICUs at Site 1, while Candida albicans was predominant at Site 2. C. parapsilosis became the most frequent species at Site 2 after 2021. C. glabrata was isolated more frequently in Site 1, whereas C. tropicalis was more frequently isolated in Site 2. A total of 14 C. auris strains were isolated, 13 of which were at the site 1. Over 90
Dermatophytes cause a wide range of superficial infections of the skin, hair and nails, with high global prevalence and considerable public health relevance. Treatment regimens for dermatophytosis are limited to few antifungal drug classes, and rising resistance—particularly to terbinafine—further compromises therapeutic efficacy. Topical antiseptics such as octenidine (OCT) may represent a promising option for infection control and local therapy. This study investigated the in vitro antifungal activity of the pure antiseptic OCT (at final assay concentrations of 0.1
Trichophyton indotineae is an emerging dermatophyte responsible for widespread, chronic, and treatment-refractory dermatophytosis worldwide; however, data from China remain limited. This study aimed to characterize the clinical manifestations, antifungal resistance, and management challenges of T. indotineae infections in Chinese patients. Three patients with disseminated dermatophytosis were evaluated clinically. Fungal isolates were identified using multilocus sequence typing and phylogenetic analysis. Antifungal susceptibility testing and sequencing of the squalene epoxidase gene were performed to assess resistance. All patients presented with extensive dermatophytosis accompanied by severe pruritus, and two had a history of residence or work in Malaysia, suggesting imported infection. Elevated serum IgE levels were observed in two cases. Molecular analyses confirmed all isolates as T. indotineae. Antifungal susceptibility testing revealed reduced susceptibility to terbinafine, with two isolates harboring the SQLE F397L mutation and one carrying the F415C mutation. Clinically, all patients showed poor response to standard antifungal regimens. High-dose itraconazole achieved partial improvement; however, relapse occurred after treatment discontinuation in all cases. These findings indicate that T. indotineae infection is characterized by chronicity, extensive involvement, and difficulty in achieving sustained remission. Antifungal resistance, particularly terbinafine resistance, together with host-related factors, may contribute to disease persistence. This study highlights the importance of accurate species identification and resistance-guided therapy, and underscores the need for optimized management strategies for this emerging dermatophyte infection.
Emergomyces (Ajellomycetaceae, Onygenales) is a genus of dimorphic fungal pathogens that cause severe, opportunistic infections around the world. We used long-read nanopore sequencing to generate de novo genome assemblies followed by comparative analyses for the type-strains of Emergomyces africanus, Emergomyces canadensis, Emergomyces crescens, Emergomyces europaeus, Emergomyces orientalis, Emergomyces pasteurianus, and Emergomyces soli. The average Emergomyces genome was found to be 32,965,087 bp in size (range 28,687,700–35,863,369 bp) with GC
INTRODUCTION:Chromoblastomycosis is a neglected tropical disease caused by melanized fungi that predominantly affects agricultural workers in endemic areas. This single-centre study from Kerala, South India, identified Fonsecaea nubica as the predominant Fonsecaea species among cultured isolates. MATERIALS AND METHODS:We conducted a prospective study of 70 suspected cases in the state of Kerala, India, from November 2022 to May 2024. Sixteen cases were confirmed or probable based on predefined criteria. Molecular identity of isolates was confirmed using ITS and CDC42 gene sequencing. Clinical, histopathological, microbiological, treatment, and outcome data were prospectively collected over a one-year follow-up period. RESULTS:Of the 16 confirmed or probable cases, nine isolates were cultured: six Fonsecaea isolates identified as F. nubica by CDC42 phylogeny (100% Fonsecaea isolates, 66.7% of cultured isolates) and three non-Fonsecaea isolates (Medicopsis romeroi, Cladosporium spp., and Lasiodiplodia spp.) identified by ITS/morphology. All cases originated from the Kottayam and Idukki districts, with 13/16 (81.3%) being male and 11/16 (68.8%) agricultural workers. Lesions predominantly affected the lower extremities (56.3%), with verrucous lesions being the most common (43.8%). All patients received itraconazole therapy, with 14/16 (87.5%) achieving clinical cure. DISCUSSION:These findings underscore the importance of molecular diagnostics in accurately characterizing the epidemiology of chromoblastomycosis in endemic regions. The emergence of F. nubica has implications for its clinical management, diagnosis, and surveillance. The study contributes valuable data to the limited molecular epidemiological literature from India and supports ongoing efforts to improve chromoblastomycosis surveillance and management in resource-limited settings.
The antifungal activity of halogenated methyl sulfones depends on both the type and number of halogen atoms in the halogenomethylsulfonyl moiety. In this study, 28 halogenomethylphenyl sulfones were evaluated for minimal inhibitory (MIC) and fungicidal concentrations (MFC) against Candida albicans. Active compounds were further tested for cytotoxicity in vitro using the Vero E6 cell line. Notably, 4-(4-chloro-3,4-dichlorophenoxy)-2-nitrophenyl difluoromethyl sulfone (compound 15) showed fungicidal activity while remaining non-toxic at effective doses. Additionally, no adverse effects were observed in Galleria mellonella larvae treated with 15 in vivo. Mechanistic studies with 15 at a sub-inhibitory concentration (2 μg/mL) showed predominant induction of necrosis in C. albicans cells (88.43
Arthroderma is a taxonomically diverse genus within the dermatophyte family (Onygenales, Arthrodermataceae) comprising primarily geophilic species typically found in animal burrows, where they feed on keratinous debris. In this study, species delineations within the genus were refined according to current taxonomic standards using the extensive array of Arthroderma strains of the BCCM/IHEM fungi collection. The methodology was based on a polyphasic approach including phenotypic analyses, multi-gene phylogenetic inference (comprising the internal transcribed spacer (ITS), β-tubulin (BT), and RNA polymerase II core subunit (RBP2) regions) and MALDI-TOF mass spectrometry. Special attention was given to the highly diverse A. quadrifidum clade which contains both geophilic and potentially zoophilic species, assessing the phylogenetic position of recently described taxa within this group. In total, 77 strains from the BCCM/IHEM collection were (re-)examined. MALDI-TOF mass spectrometry was able to correctly identify 92
Saccharomyces cerevisiae has increasingly been recognized as an opportunistic pathogen. Sterile-site infections remain rare but are associated with substantial morbidity and mortality, especially in critically ill patients. This study aimed to characterize the epidemiological, clinical, and microbiological characteristics of sterile-site S. cerevisiae infections. We performed a retrospective analysis of all patients with S. cerevisiae isolated from sterile body sites between January 2019 and December 2025. Demographic data, underlying conditions, probiotic exposure, antifungal therapy, and outcomes were collected, and antifungal susceptibility testing was performed. Among 196 patients with S. cerevisiae isolates, 30 (15
