Mucormycosis remains a devastating fungal infection. Albumin has been proposed as a host defense mechanism against Mucorales with direct antifungal effects. In both matched and unmatched case-control analyses, serum albumin levels were lower in pediatric cancer patients with mucormycosis (N = 12) compared to children with other infections. Children with mucormycosis that died had significantly lower albumin levels than those who survived, whereas albumin levels were not associated with mortality in children with other infections. In addition, hypoalbuminemia preceded mucormycosis suggesting it may serve as a risk factor and potential therapeutic target.

Invasive fusariosis is a rare but often fatal infection in immunocompromised patients. However, data in allogeneic hematopoietic cell transplantation (HCT) are limited. Using a nationwide Japanese transplant registry database, we identified patients who underwent allogeneic HCT between 2008 and 2021 and subsequently developed invasive fusariosis. We conducted questionnaire survey to characterize invasive fusariosis and identify factors associated with early mortality. Thirty-one patients were included. Invasive fusariosis developed at a median of 24 days after HCT. Neutropenia was present in 23 patients (74.2%), and corticosteroids were administered to 23 patients (74.2%). The most commonly involved sites were the bloodstream (71.0%), skin (54.8%), and the respiratory tract (35.5%). Serum (1→3)-β-D-glucan (BDG) was positive in 26 of 31 patients (83.9%) within 2 weeks after diagnosis, whereas BDG positivity preceded the diagnosis in only 15 of 29 evaluable patients (51.7%). Twenty-two (71.0%) died within 30 days after the diagnosis. BDG value normalized to the upper limit of normal (BDG/ULN) within 1 week before diagnosis was significantly lower in 30-day survivors than in non-survivors (median, survivor 0.55 vs. non-survivor 2.94). A pre-diagnostic BDG/ULN of 1.27 predicted 30-day mortality with a sensitivity of 85.7% and a specificity of 81.0%. Among 23 patients who developed invasive fusariosis during neutropenia, all seven 30-day survivors achieved neutrophil recovery, whereas none of the non-survivors did. In conclusion, invasive fusariosis after allogeneic HCT was associated with extremely poor outcomes, particularly in patients with persistent neutropenia. Elevated BDG levels around the time of diagnosis were strongly associated with early mortality.

Candidemia is associated with substantial mortality in critically ill patients, and early identification of patients at increased risk of death remains challenging. The delta neutrophil index (DNI), an automated hematological parameter reflecting circulating immature granulocytes, has been proposed as a prognostic marker in sepsis, but its role in candidemia remains unclear. This retrospective study included adults who developed candidemia during intensive care unit hospitalization between January 1, 2020, and December 31, 2023; patients with neutropenia, haematological malignancy receiving ongoing chemotherapy, or granulocyte colony-stimulating factor therapy were excluded. Patients were classified as survivors or non-survivors according to 28-day all-cause mortality after blood culture collection. DNI, leukocyte count, C-reactive protein, and procalcitonin were evaluated 24 hours before, at the time of, and 24 hours after blood culture collection. Multivariable logistic regression identified factors independently associated with mortality, and receiver operating characteristic analysis assessed the prognostic performance of DNI. Among 246 patients, 132 survived and 114 died. Non-survivors had higher APACHE II scores and more frequent acute kidney injury. DNI and procalcitonin levels were significantly higher in non-survivors at all three time points. In the primary multivariable model, acute kidney injury, DNI at blood culture collection, and procalcitonin at blood culture collection were independently associated with mortality; the association of DNI was attenuated and no longer statistically significant after further adjustment for Candida species and antifungal therapy. DNI showed limited discrimination, with area under the curve values ranging from 0.608 to 0.625; the highest value was observed at blood culture collection (0.625), with a cutoff of 2.4, 43.0% sensitivity, and 82.6% specificity. DNI may aid mortality risk stratification in candidemia but should not be used as a standalone prognostic marker.

Filamentous basidiomycetes are increasingly recognized as causes of diverse human disease, yet knowledge of their clinical spectrum, diagnosis, treatment, antifungal susceptibility, and outcomes remains fragmented. We systematically reviewed published clinically significant human infections caused by filamentous basidiomycetes. Clinical, microbiological, radiological, treatment, susceptibility, and outcome data were extracted, cases from India were compared with those from the rest of the world (RoW), and logistic regression identified independent mortality predictors. Antifungal susceptibility data were summarized descriptively. We included 253 cases from 112 studies, comprising 56 from India and 197 from RoW. Respiratory or sinonasal disease without demonstrated tissue invasion predominated, although invasive and localized/non-invasive disease also occurred. Among patients with known immune status, 61.7% were immunocompetent, significantly more frequently in India. Schizophyllum commune (38.3%), Bjerkandera adusta (29.2%), and Hormographiella aspergillata (9.5%) predominated. Molecular sequencing was used for species-level identification in 62.5% of cases. Outcomes were available for 238 patients; 33 died (13.9%). Immunocompromised status (adjusted odds ratio [aOR], 7.12; 95% CI, 1.44-35.19) and histologic invasion (aOR, 3.19; 95% CI, 1.10-9.28) independently predicted mortality, whereas surgery was associated with lower observed mortality (aOR, 0.07; 95% CI, 0.01-0.66), although causality cannot be inferred. Amphotericin B and mold-active triazoles, particularly voriconazole, posaconazole, and isavuconazole, showed the most favorable in vitro activity, whereas fluconazole, 5-flucytosine, and echinocandins showed limited activity. Filamentous basidiomycetes cause a broad spectrum of disease in immunocompetent and immunocompromised hosts. Molecular identification is essential for accurate diagnosis, while immune status and tissue invasion are important independent determinants of adverse clinical outcomes.

Vulvovaginal candidiasis is a common fungal infection, mainly due to Candida species, affecting two-thirds of women globally at least once in their lifetime. Here, we conducted a systematic review and meta-analysis (PROSPERO ID: CRD420261368975) of the epidemiology, aetiology, and drug resistance profiles of vulvovaginal Candida infections and VVC in Cameroon. Databases were queried to identify all eligible papers. Data were extracted, and the quality bias of studies was assessed. Random effect models were used to estimate pooled proportions of primary outcomes. Thirty-four studies were included. The pooled proportions of vulvovaginal Candida infections and VVC were 33.3% (95% CI 25.5 - 41.6%, p < 0.0001) and 31.6% (95% CI 26.9 - 36.4%, p < 0.0001), respectively. Candida albicans (23.3%, 95%CI 17.9 - 29.1%, p < 0.0001) was the most frequently isolated causative species, followed by Nakaseomyces glabratus (formerly C. glabrata) (2.3%, 95%CI 0.9 - 4.2%, p < 0.0001) and Pichia kudriavzevii (formerly C. krusei) (1.3%, 95%CI 0.5 - 2.5%, p < 0.0001). Pregnancy status, diagnostic methods, and human immunodeficiency virus infection influenced the proportions of these species. Two primary azoles were least effective against C. albicans, with the following resistance levels: fluconazole (51.1%, 95% CI 21.2 - 80.7%, p < 0.0001) and itraconazole (50.5%, 95% CI 41.3 - 100%, p < 0.0001). Evidence of drug profiles for non-albicans species is limited. The findings highlight the substantial burden of VVC, the predominance of C. albicans, and high azole resistance in Cameroon. They underscore the need for standardised diagnostic approaches, broader epidemiological surveillance, and evidence-based preventive strategies.

Penguins are highly susceptible to airborne mycoses, and aspergillosis due to Aspergillus fumigatus (recently classified as priority pathogen by WHO) is common in captivity; however, environmental fungal diversity and exposure risk in natural, non-temperate breeding habitats remain poorly described. We aimed to characterize the seasonal burden and diversity of culturable fungi in wild king penguin (Aptenodytes patagonicus) colonies and to assess A. fumigatus diversity and phenotypes. During one year, monthly environmental sampling was performed from four different soils of Crozet archipelago, in French Southern Territories, around three penguin colonies. Samples were cultured on malt extract agar at 35 ± 2°C. Isolates were quantified (CFU) and identified by microscopy, MALDI-TOF MS, and DNA sequencing. A. fumigatus isolates underwent genotyping and phenotyping for antifungal susceptibility, as well as for tolerance to high salinity and extreme temperatures. Overall, fungal loads in penguin environments showed marked seasonality (3-1 100 CFU/month), peaking during breeding/chick rearing summer period (∼22% positive sites). After April, fungal burden declined (mean 150 CFU/month; 8.8% positive sites). Aspergillus section Fumigati represented 21-100% of isolates (150-950 CFU/month). A. fumigatus genotypes were diverse, with no detected antifungal resistance or extreme growth phenotypes. Fungal burden in penguin natural habitats was closely linked to bird presence and breeding activity. These findings provide new insights into fungal exposure in wild groups and emphasize the importance of a One Health approach to better understand the interactions between environment, wildlife, and infectious disease risk in fragile ecosystems.

Recurrent vulvovaginal candidiasis (RVVC) is a condition characterized by recurrent episodes of vulvovaginal candidiasis, caused primarily by Candida albicans. Host genetic variations may play a role in the susceptibility to this disease. We performed whole-exome sequencing (WES) in patients with RVVC to identify potentially deleterious genetic variants in candidate genes, assess their impact on gene expression. We searched for patients with severe RVVC (>10 episodes per year) and who had additional affected family member(s). WES was performed on gDNA from the index patients. Vaginal scraping samples were obtained from the affected females, and total RNA was obtained to evaluate the expression of candidate genes by qPCR. We identified 12 adult females affected with severe RVVC across 11 families, of whom three had more than one affected female. In silico analyses of WES results revealed potentially deleterious variants in MUC4, MUC5B, and MUC21 genes. A significant decrease in the expression of the MUC5B and MUC21 genes was observed in patients with RVVC compared to healthy women. These results suggest that potentially deleterious variants could affect the expression of the genes encoding different members of the mucin family, indicating that mucins may play a significant role in the pathogenesis of RVVC.

The Aspergillus galactomannan chemiluminescence immunoassay (GM-CLIA) is a novel non-culture-based test applied in the detection of GM antigen in serum and bronchoalveolar lavage fluid (BALF). This multicenter, retrospective, and controlled study aims to investigate its diagnostic value for invasive aspergillosis (IA). A total of 246 serum and 228 BALF samples were obtained from IA patients (n = 229) and non-IA (n = 236) patients between March 2023 and July 2024. The performance of GM-CLIA was compared with that of Aspergillus GM sandwich enzyme immunoassay (GM-EIA) through Spearman rank correlation analysis and assessed via sensitivity, specificity, positive/negative predictive values (PPV/NPV), and receiver operating characteristic (ROC) curve analysis. Analytical performance was evaluated through interference, precision, limit of detection (LoD), and cross-reactivity experiments.The sensitivity, specificity, PPV, and NPV of serum GM-CLIA were 93.97%, 97.46%, 97.32%, and 94.26%, respectively. For BALF GM-CLIA, the corresponding values were 93.58%, 95.76%, 95.33%, and 94.17%. ROC analysis yielded high area under the curve (serum: 0.977; BALF: 0.982) with optimal cut-offs of 0.625 (serum) and 0.615 (BALF). The levels of GM by CLIA and EIA (rs = 0.838, P < 0.0001) strongly correlated. No interference was observed from hemoglobulin, bilirubin, or triglycerides at certain concentrations. Repeatability, indoor, and inter-batch precision met predefined criteria, with no cross-reactivity in non-Aspergillus pathogens. The LoD for detecting GM-CLIA was 0.09 ng/mL. In summary, GM-CLIA was evaluated in both sample types, demonstrating high specificity and sensitivity in diagnosing IA. Thus, clinical implementation of CLIA may significantly improve diagnostic efficiency and patient outcomes.

Candida albicans is a commonly encountered dimorphic fungus that normally resides in the human body. Once the host is immune-compromised or endures long-term antibiotic treatment, C. albicans will transform into an opportunistic pathogen that can cause from superficial mucosal diseases (e.g., oropharyngeal candidiasis) to life-threatening invasive infections (e.g., candidemia). Since the resistance rate of clinical C. albicans is rapidly increasing, there is an urgency to expand the current antifungal armamentarium. It has been shown that a growing body of host receptors can recognize the cell wall components of C. albicans (e.g., β-glucan, chitin, and mannan), and trigger potent innate immune responses with enhanced phagocytosis, reactive oxygen species, and inflammatory cytokine production. In this review, we classify the host receptors into two categories: the receptors that directly interact with the epitopes of C. albicans, and those that act as co-receptors to aid in epitope recognition. The former receptors include Dectin-1/2/3, Mincle, MR, DC-SIGN, MBL, CR3, LYSMD3, NKp30, and SPINK7, whereas the latter ones consist of TLR2/4, EphA2/B2, galectin-3, gC1qR, AhR, EGFR, and HER2. We not only characterize the antifungal modes of these host receptors during C. albicans infection, but also summarize the features underlying the recognition of C. albicans epitopes by these receptors. The advancements in PRRs can largely expand our scientific understanding of antifungal mechanisms, and lay a solid foundation for the development of new antifungal agents for the clinical treatment of systemic infections caused by C. albicans.

Candidozyma auris (formerly Candida auris) is an emerging multidrug-resistant fungus with limited genomic epidemiological data from Malaysia. This study investigated the genomic epidemiology, clinical characteristics and antifungal susceptibility of C. auris outbreak isolates using an integrated whole-genome sequencing (WGS) approach. Eleven clinical C. auris isolates from five healthcare facilities across three Malaysian states were analysed alongside clinical and epidemiological data. Antifungal susceptibility testing was performed for azoles, echinocandins, amphotericin B, flucytosine, and manogepix. Among 11 patients, seven had candidemia and four were colonized. Median age was 48 years, with diabetes mellitus, chronic kidney disease, and hypertension as the most common comorbidities. All candidemia patients had urinary and central venous catheters; 71% required mechanical ventilation, 43% had haemodialysis and recent surgery, respectively. Recent antibiotic exposure was common, whereas none had prior antifungal therapy. All isolates belonged to Clade I but separated into distinct genomic clusters, supporting healthcare-associated transmission within clusters and simultaneous circulation of multiple genomic groups. All Johor-associated isolates were fluconazole resistant and carried ERG11 K143R and CDR1 V704L substitutions. An ERG5 variant was detected in non-Johor isolates with amphotericin B minimum inhibitory concentrations (MICs) ≥ 1 µg/ml. The MICs for other antifungals remained low across isolates. Echinocandin therapy was initiated in 27% of patients, with one survivor. Our C. auris showed genomic diversity, distinct healthcare-associated clustering, and variable antifungal susceptibility. Integrating WGS with clinical and susceptibility data enhanced outbreak investigation of C. auris.

Fungal pneumonias and tuberculosis (TB) remain major causes of mortality among people living with advanced HIV disease (PLWHA). Their overlapping clinical manifestations delay diagnosis in developed and resource-limited settings, with greater impact where access to rapid diagnostic tools is limited. This study evaluated the performance of a multiplex quantitative PCR (qPCR) assay for simultaneous detection of Histoplasma capsulatum, Cryptococcus neoformans, Pneumocystis jirovecii, and Mycobacterium tuberculosis complex in respiratory samples from PLWHA. A cross-sectional study was conducted at the Instituto Nacional de Infectologia Evandro Chagas (Rio de Janeiro, Brazil) between December 2023 and March 2025. Adults with HIV infection (CD4 < 200 cells/mm[3]) and clinical or radiological evidence of pulmonary infection were enrolled. Standard diagnostic methods included culture, microscopy, antigen detection (CrAg-LFA, urinary Histoplasma antigen, TB-LAM), GeneXpert® MTB/RIF, and commercial qPCR for P. jirovecii. The multiplex assay targeted the ITS region (H. capsulatum and C. neoformans), mtLSU (P. jirovecii), and IS6110 (M. tuberculosis). Among 198 screened participants, 88 met inclusion criteria (mean CD4 count: 56 cells/µl). Diagnosis included TB (56.8%), pneumocystosis (34.1%), histoplasmosis (10.2%), and cryptococcosis (11.4%); 25% presented coinfections. The multiplex qPCR showed 100% sensitivity for histoplasmosis, 80% for pneumocystosis, and 40% for both cryptococcosis and TB, with specificities ≥ 82% and 100% for TB. Overall accuracy ranged from 66% to 86%. Mortality was 12.5%, highest among cryptococcosis cases (20%). The assay provided accurate detection of H. capsulatum and P. jirovecii, although performance was limited for TB and cryptococcosis, supporting its use as a complementary molecular tool for differential diagnosis in PLWHA.

Contemporary data on risk factors for invasive candidiasis (IC) in solid organ transplant recipients (SOTr) are rare. This follow-up study on a large multicenter cohort study, nested within the Swiss Transplant Cohort Study, identifies risk factors for IC during the first year posttransplant. Among 4755 and 4519 SOTr identified between 0-3 months (early) and 4-12 months (late) posttransplant, 90 (1.9%) and 48 (1.1%) had 109 and 50 episodes of IC, respectively. Posttransplant Candida colonization (HR: 3.2; 95% CI: 1.67-6.14; P < .001), and posttransplant anastomosis (HR: 3.14; 95% CI: 1.74-5.69; P < .001) and bleeding/vascular complications (HR: 3.66; 95% CI: 2.38-5.62; P < .001) were independent risk factors for early IC, while transplantation between 2015 and 2020 (HR: 0.57; 95% CI: 0.38-0.88, P = .011) and male sex (HR: 0.63; 95% CI: 0.59-0.88; P = .026) demonstrated lower risk for early IC in multivariable analysis for all transplant types. Systemic antifungal prophylaxis (HR: 30.9; 95% CI: 4.9-194; Padj = .003) was associated with increased risk of early IC in kidney/kidney-pancreas recipients in univariable analysis. Posttransplant anastomosis (HR: 4.39; 95% CI: 2.49-7.72; Padj < .001) and surgical site/surgical other complications (HR: 3.62; 95% CI: 2.03-6.46; Padj < .001) were independent risk factors for late IC in univariable analysis for all transplant types. In conclusion, this study highlights the impact of posttransplant Candida colonization and posttransplant surgical complications on the occurrence of IC. These findings can support the design of more effective prophylactic strategies and inform clinical practice in this vulnerable patient population.

Mucormycosis is a severe fungal infection with high mortality in immunocompromised patients. Although most cases occur sporadically in the community setting, there are reports of healthcare-associated outbreaks of mucormycosis. We describe the investigation and clinical features of an outbreak of mucormycosis caused by Rhizomucor pusillus in a hematopoietic stem cell transplant (HSCT) unit in Brazil. Cases were screened through the hospital records, defined according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium criteria, and classified as HSCT unit-acquired or not. Mucormycosis incidence was monitored from 2 years before the index case until 2 years after the last case. The clinical course of identified cases and potential environmental exposure data were recorded. Microbiological samples were identified with conventional methods and internal transcribed spacer sequencing; whole genome sequencing was performed for phylogenetic analysis. Potential source investigation was conducted according to the US Centers for Disease Control recommendations. Four proven cases of HSCT-unit-acquired mucormycosis were identified over a 10-month period. Rhizomucor pusillus was identified in three of the four patients. Disseminated disease, beginning with pulmonary infection, was the most common clinical presentation. Survivors (75%) received treatment with lipid complex amphotericin B, isavuconazole, and/or surgical resection. Environmental investigation was negative and phylogenetic analysis demonstrated that isolates were not clonal. Following air system maintenance, no further cases were identified. We characterize the first reported outbreak investigation of mucormycosis caused by R. pusillus in a Brazilian HSCT unit, with favorable outcomes in most cases despite aggressive clinical presentation. Despite the lack of clonality and negative environmental investigation, epidemiological evidence strongly suggests nosocomial transmission.

Candidozyma auris (Candida auris) candidemia is a serious healthcare-associated infection with substantial mortality and limited treatment options. We retrospectively evaluated adult patients with C. auris candidemia at a tertiary care center between June 2022 and December 2025 to describe clinical management, microbiological outcomes, antifungal susceptibility, and factors associated with 28-day mortality. The descriptive cohort included 108 patients; mortality status was available for 107. Most patients (92.6%) were in intensive care at candidemia onset, and among evaluable patients, 76.1% had prior C. auris colonisation detected. Twenty-eight-day mortality was 41.1% (44/107). Non-survivors were older and had higher Charlson Comorbidity Index, Pitt bacteremia, and Sequential Organ Failure Assessment (SOFA) scores. Central venous catheter removal was more frequent among survivors (72.7% vs. 45.0%; P = .012), although removal timing and time to initiation of effective antifungal therapy did not differ significantly between groups. In multivariable analysis, Charlson Comorbidity Index (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.02-1.44) and SOFA score (aOR, 1.16; 95% CI, 1.05-1.27) were independently associated with 28-day mortality. Resistance rates were 95.1% for fluconazole, 31.2% for amphotericin B, and 1.3% for both anidulafungin and micafungin; multidrug resistance rate was 28.6%, and no isolate met the definition of pandrug resistance. Mortality in C. auris candidemia was mainly associated with baseline comorbidity burden and acute organ dysfunction. Local susceptibility surveillance and early recognition of high-risk patients may support treatment and infection-control strategies.

Invasive mold disease is associated with high mortality in immunosuppressed patients. While Aspergillus spp. and the Mucorales are well known, several other molds have emerged that cause infections and even outbreaks in susceptible hosts. These include Fusarium spp., Scedosporium spp., Lomentospora prolificans, and several others. The principles of preventing nosocomial mold infections include use of high-efficiency particulate air filters, removal of any potential sources of contamination, and risk-assessment of construction sites in adjacent areas. However, there is limited information on the approaches to assessment and management of outbreaks when there is a cluster of rare mold infections. The incubation period of rare and emerging molds is unknown and ascertaining whether the origin is nosocomial or community-acquired is difficult. Surveillance may be required to determine whether cases are part of an ongoing problem. The environmental niches of the rare molds are unique; e.g., Fusarium spp. are associated with hospital water distribution systems. They also cause outbreaks of fungal keratitis. Many rare molds are seen in cases of medicinal product contamination and managing such outbreaks requires support from and coordination by national agencies. Environmental precautions around patients and construction activities should be reassessed during outbreaks. A systematic approach is required when evaluating a cluster or even an isolated nosocomial case. Surveillance systems should be strengthened. This review summarizes the information available on outbreaks of rare and emerging molds. We further discuss a set of actions that may be undertaken in the event of an outbreak.