Medical mycology最新文献

This study evaluated the predictive value of Krebs von den Lungen-6 (KL-6) for the development of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) and its association with mortality in critically ill COVID-19 patients. A retrospective single-center cohort study was conducted on critically ill COVID-19 patients who required high-flow oxygen or mechanical ventilation between January 2021 and June 2023. Serial serum KL-6 levels were measured at admission and weekly thereafter. The predictive performance of initial KL-6 was assessed using ROC curve analysis, and risk factors for CAPA and 30-day mortality were analyzed using multivariable models. Among 238 patients, 25 (10.5%) developed CAPA. Initial KL-6 demonstrated good discriminative ability for CAPA prediction (AUC 0.745; 95% CI: 0.685-0.799), with an optimal cutoff of 270.9 U/mL (sensitivity: 88.0%, specificity: 55.4%). KL-6 ≥ 270.9 U/mL remained independently associated with CAPA (aHR: 9.66; 95% CI: 2.28-40.89) after multivariable analysis. Serial measurements showed a trend toward a greater increase in KL-6 levels among CAPA patients than non-CAPA patients (median difference: 259.9 vs. 73.0 U/mL, P = 0.053). Additional independent predictors of CAPA included inotropic/vasopressor support, diabetes mellitus, and tocilizumab use. CAPA patients had higher all-cause 30-day mortality (60.8% vs. 45.2%; P = 0.020), which remained significant after adjustment (aHR: 2.19; 95% CI: 1.08-4.15). Furthermore, KL-6 was independently associated with 30-day mortality (aHR: 1.03 per 100 U/mL; 95% CI: 1.00-1.07). These findings suggest that KL-6 is a promising biomarker for predicting CAPA and mortality in critically ill COVID-19 patients.

Data on the coinfection of molds are limited. Therefore, we systematically investigated mucormycosis coinfection in patients with morphologically proven aspergillosis. The medical records of adult patients with proven aspergillosis and available formalin-fixed paraffin-embedded (FFPE) tissue sections were retrospectively reviewed at a tertiary hospital between January 2019 and July 2024. The fungal culture results were reviewed and polymerase chain reaction (PCR) was performed to detect Aspergillus- and Mucorales-specific DNA using FFPE tissues. A positive Mucorales PCR test was confirmed when positive results were obtained for both the 18S and 28S targets. A total of 49 patients with proven aspergillosis were analyzed. The sterile specimen was not found to contain Mucorales. However, fungal cultures from a non-sterile site (endotracheal aspirate) revealed the presence of Aspergillus niger and Cunninghamella spp. in 1 (2%) of 49 patients (Patient A). A positive Mucorales-specific PCR result was obtained for one patient (2%) while positive Aspergillus- and Mucorales-specific PCR results were obtained for five patients, including Patient A (10%). Overall, 6 (12%) of the 49 patients with proven aspergillosis were found to be coinfected with mucormycosis. Coinfection with mucormycosis was significantly more associated with rhino-paranasal sinuses (33% vs. 2%, P = .03). In-hospital mortality was not found to significantly differ between patients with mucormycosis coinfection and those with aspergillosis alone (33% [2/6] vs. 14% [6/43], P = .24). Approximately one-tenth of patients with proven aspergillosis had molecular or microbiologic evidence of mucormycosis coinfection. Further studies are needed to highlight the clinical implications of the molecular evidence of mucormycosis coinfection in patients with proven aspergillosis.

Candida albicans is a major human fungal pathogen; however, limited antifungal agents, undesirable drug side effects, and ineffective prevention of drug-resistant strains have become serious problems. Chitosan is a nontoxic, biodegradable, and biocompatible linear polysaccharide made from the deacetylation of chitin. In this study, a ZCF31 putative transcription factor gene was selected from a previous mutant library screen, as zcf31Δ strains exhibited defective cell growth in response to chitosan. Furthermore, chitosan caused notable damage to zcf31Δ cells; however, ZCF31 expression was not significantly changed by chitosan, suggesting that zcf31Δ is sensitive to chitosan could be due to changes in the physical properties of C. albicans. Indeed, zcf31Δ cells displayed significant increases in cell wall thickness. Consistent with the previous study, zcf31Δ strains were resistant to calcofluor white but highly susceptible to SDS (sodium dodecyl sulfate). These results implied that chitosan mainly influences membrane function, as zcf31Δ strengthens the stress resistance of the fungal cell wall but lessens cell membrane function. Interestingly, this effect on the cell surface mechanics of the C. albicans zcf31Δ strains was not responsible for the virulence-associated function. RNA-seq analysis further revealed that six mannosyltransferase-related genes were upregulated in zcf31Δ. Although five mannosyltransferase-related mutant strains in the zcf31Δ background partially reduced the cell wall thickness, only zcf31Δ/mnn45Δ showed the recovery of chitosan resistance. Our findings suggest that Zcf31 mediates a delicate and complicated dynamic balance between the cell membrane and cell wall architectures through the mannosyltransferase genes in C. albicans, leading to altered chitosan susceptibility.

Vulvovaginal candidiasis (VVC) is an inflammation caused by Candida albicans with a higher recurrence rate in individuals deficient in Card9. This study aimed to elucidate the mechanisms underlying this increased susceptibility. Estrogen-treated Card9-/- mice infected with C. albicans were used to model Card9 deficiency-related VVC. Our findings indicate that Card9 deficiency leads to a reduction in Th17 cells, interleukin (IL)-17-producing γδ T cells, and IL-17A secretion, weakens epithelial tight junctions, and reduces antimicrobial peptide secretion, leading to persistent fungal invasion. This persistent invasion results in excessive neutrophil recruitment and activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) and absent in melanoma 2 inflammasomes (AIM2), causing mucosal damage. In conclusion, Card9 deficiency compromises the vaginal epithelial barrier, prolongs C. albicans infection, and increases inflammation, highlighting the critical role of Card9 in maintaining immune function of vaginal mucosa.

Access to antifungal agents for the treatment of invasive fungal infections (IFIs) varies significantly between countries. Limited access or high cost may contribute to the burden of IFIs. We aimed to investigate the availability and cost of antifungal treatment for IFIs in Vietnam. Procurement data from 2018 to 2022 was collected from the Drug Administration of Vietnam website. We calculated the cost per defined daily dose (DDD) and identified the manufacturing countries. We explored the pharmacotherapy cost of the four major IFIs if first-line agents were used in accordance with the Vietnam 2021 antifungal prescribing guideline. We also estimated the treatment expenditure in 2020 based on the estimated disease burden previously published and suggested cost-saving measures. At least 57.6 million USD was spent on 15.5 million DDD of antifungals in five years. Seven systemic antifungal agents were available in Vietnam. Caspofungin and micafungin were the least used but most expensive, whereas fluconazole and itraconazole were the most consumed but cheapest antifungals. Vietnam manufactured 70% of azole antifungals and relied on imports for the remaining antifungals consumed. We estimated the first-line pharmacological treatment for the estimated cases of four IFIs in 2020 to cost at least 209.1 million USD, which exceeded the actual spend in 2020. We discovered that antifungal agents for IFIs impose a substantial economic burden on Vietnam's healthcare system. We highlight the need for cost-effectiveness studies of expensive first-line medications. Efforts to mitigate this economic burden should include antifungal stewardship, prevention of IFIs, and sourcing from cost-effective manufacturers.

The anthropophilic dermatophyte Trichophyton interdigitale and its counterpart T. mentagrophytes are phylogenetically closely related species. In India, the most common endemic dermatophyte species belongs to the T. indotineae. The internal transcribed spacer genotype VIII within this species complex was recently renamed as T. indotineae based on its rapid emergence in India and its elevated virulence and terbinafine resistance. While humans are considered a source of T. interdigitale infection, animals are considered a source of T. mentagrophytes. For T. indotineae it is not known whether infections occur anthropophilic or zoonotic, as there is very little data on its origin and transmission. Additionally, the environmental source of T. indotineae is unknown. In the current study, we have performed the molecular typing method amplified fragment length polymorphism on 24 T. indotineae isolates to determine the genetic diversity among animal and human origin isolates and compare it to related species. Additionally, we performed antifungal susceptibility testing by standard micro broth dilution methods against common antifungals. In contrast to the T. interdigitale which showed significant genetic variability between isolates from different cities, T. indotineae isolates demonstrate minimal genetic variability, also between samples from animals and humans, highlighting the possibility of zoonotic transmission of this virulent dermatophyte. Reduced susceptibility was found for terbinafine and griseofulvin.

Histoplasmosis is a life-threatening opportunistic infection in individuals with advanced HIV disease, particularly in endemic regions such as Latin America. Early diagnosis is crucial for reducing mortality but remains underdiagnosed due to non-specific clinical presentations and limited diagnostic access. This study evaluates the impact of systematic histoplasmosis screening over 18 months (March 2021-September 2022) using the Histoplasma urinary antigen detection test in people living with HIV (PLHIV) receiving outpatient care or hospitalized at a reference center in Southern Brazil. A retrospective analysis was conducted on PLHIV screened with the Clarus® Histoplasma GM enzyme immunoassay (HGM-EIA, IMMY, USA). Inclusion criteria comprised a recent HIV diagnosis (≤ 30 days), poor adherence to or abandonment of antiretroviral therapy (>90 days), CD4 + count < 200 cells/mm³, or clinical/radiological findings suggestive of histoplasmosis. Clinical, laboratory, and treatment data were assessed, along with 90-day outcomes. Among 287 PLHIV screened, Histoplasma antigen was detected in 9.1% (26/287), including 19.6% of hospitalized patients and 6.4% of outpatients. Overall mortality was 24%, with a higher rate among inpatients (27.3%). Fever, neurological impairment, and lung opacification were more frequent in hospitalized cases. Amphotericin B deoxycholate was more commonly administered to inpatients (63.6% vs. 25%). Mortality at 90 days was significantly higher in patients with a histoplasmosis case-fatality score ≥ 5 (66.7% vs. 33.3%, P = .016). Systematic screening enhances early detection of histoplasmosis, facilitating timely treatment and reducing hospitalizations and mortality.

Amphotericin B remains an important treatment for multidrug-resistant Candida auris. Antifungal susceptibility testing of amphotericin B in C. auris can vary depending on the methodology used. Here, we compared the Etest method and the Clinical and Laboratory Standards Institute broth microdilution reference method for amphotericin B against 60 clinical C. auris isolates from the four major clades. The minimum inhibitory concentrations differed significantly by method (P-value, <.0001), and discrepancies were observed in the interpretation of resistance (categorical agreement, 88.3%; very major error, 33.3%). Broth microdilution may represent a more conservative approach for detecting amphotericin B resistance in C. auris.

Scedosporium and Lomentospora species are emerging fungal pathogens capable of causing severe infections in both immunocompetent and immunocompromised individuals. Previous environmental surveys have suggested potential associations between these fungi and various soil chemical parameters, though the relative influence of human activity versus environmental factors has not been systematically evaluated. Here, we conducted a comprehensive survey of 406 soil samples from 132 locations across Taiwan, analyzing fungal abundance alongside soil physicochemical parameters and the Human Footprint Index (HFI). We recovered 236 fungal isolates comprising 10 species, with S. boydii (32.2%), S. apiospermum (30.9%), and S. dehoogii (14.4%) being the most prevalent. The highest fungal burdens were observed in urban environments (up to 1293 CFU/g), particularly in public spaces and healthcare facilities. Statistical analysis revealed a significant positive correlation between fungal abundance and HFI (r = 0.143, P = .005), while soil chemical parameters including nitrogen, carbon, pH, electrical conductivity, and various base cations showed no significant associations despite their wide ranges. These findings indicate that anthropogenic disturbance of environments, rather than soil chemistry, is the primary driver of Scedosporium and Lomentospora distribution in Taiwan. This understanding holds important implications for predicting infection risks and developing targeted public health strategies, particularly in rapidly urbanizing regions. Future studies incorporating more specific indicators of human impact may further elucidate the mechanisms underlying these distribution patterns.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has emerged as a complication following COVID-19 infections. This study aimed to evaluate the clinical and epidemiological data of CAPA cases in a tertiary hospital. Conducted retrospectively from February 2020 to January 2024, it involved the analysis of medical records to identify CAPA cases based on the diagnostic criteria established by the European Confederation of Medical Mycology and the International Society for Human and Animal Mycology. Seven patients were identified as possible CAPA cases, of whom 71.43% had pre-existing comorbidities. All patients received corticosteroid therapy, and 42.86% required prolonged mechanical ventilation. The study revealed a high mortality rate, with 71.43% of patients succumbing to the condition. The diagnosis of CAPA is challenging due to the invasiveness of definitive tests, such as biopsies, and the lack of resources for essential diagnostics like galactomannan detection. Despite the limited sample size, the findings align with existing literature, indicating a high prevalence of comorbidities, prior corticosteroid use, and mechanical ventilation as significant risk factors. This study underscores the critical need for heightened awareness, early diagnosis, and proactive management strategies for CAPA in severely ill COVID-19 patients to reduce risks and improve patient outcomes.