Mycopathologia最新文献

Background: Voriconazole (VRC) has been used as an alternative treatment for talaromycosis. However, there are few studies reporting the VRC plasma concentration in patients with talaromycosis. The purpose of this study was to analyze the correlations between VRC initial steady-state trough concentration and clinical outcomes.

Methods: We prospectively enrolled patients who were diagnosed with talaromycosis and received VRC as initial antifungal treatment regime. Medical information, VRC initial steady-state trough concentration, clinical outcomes and adverse events (AEs) were recorded for analysis.

Results: This study included 69 patients with talaromycosis receiving VRC treatment, including 38 HIV-positive patients and 31 HIV-negative patients. The average age of the HIV-positive patients was 42 years, and that of the HIV-negative patients was 51 years. After 12 weeks of antifungal treatment, 55 patients achieved clinical remission, 3 patients were transferred to amphotericin B treatment because of persistent clinical symptoms, and 5 patients died, 2 patients discontinued VRC treatment due to AEs. Follow up to 6 months, a total of 14 AEs were observed in 12 patients, and 3 patients discontinued VRC treatment due to AEs. The average VRC initial steady-state trough concentration was 5.26 mg/L, with a range of 0.23-16.95 mg/L, indicating high variability. No correlation was found between the VRC initial steady-state trough concentration and treatment failure (P = 0.079). A significant correlation between AEs and the VRC initial steady-state trough concentration was found (P = 0.048). The VRC initial steady-state trough concentration threshold for AEs was 5.88 mg/L according to the ROC curve analysis. In addition, there was a significant correlation between mortality and the APACHE II score (P = 0.029). The risk of death significantly increased when the APACHE II score was > 10.

Conclusion: Voriconazole is an effective antifungal drug for talaromycosis in patients with APACHE II scores < 10. VRC steady-state trough concentration may not be significantly correlated with poor prognosis. A high VRC trough concentration was significantly correlated with AEs, and it may promote the management of AEs.

Fungal keratitis, which is caused primarily by Neocosmospora and Fusarium species, is a significant global health issue that affects more than a million people annually in tropical and subtropical regions. Neocosmospora solani (formerly Fusarium solani) is a leading cause of corneal infections, along with members of the Fusarium oxysporum species complex (FOSC). This study provides new insights by reporting a series of ocular fusariosis cases caused by FOSC members and presenting molecular evidence linking specific haplotypes within FOSC to human infections. We describe three cases of Fusarium keratitis selected from a comprehensive review of clinicopathological data in our institution's archives. These cases were chosen for their distinctive clinical presentations and the involvement of less common Fusarium species. Two of these patients were diagnosed with keratitis and anterior endophthalmitis, and the third patient had a corneal ulcer previously treated with topical antivirals and antibiotics. All patients were successfully treated with topical amphotericin B. The Fusarium isolates from these patients were subjected to detailed molecular characterization, including DNA sequencing (tef1α, rpb2, CaM, tub2, and LSU), amplified fragment length polymorphism (AFLP) marker analysis, and MALDI-TOF MS analysis. Remarkably, our study reports the first case of human infection by F. veterinarium, alongside cases involving F. contaminatum and F. curvatum. Furthermore, a molecular survey using haplotypic networks based on tef1α sequences identified genotypes associated with human infections and revealed the emergence of F. veterinarium clade VII. Our findings emphasize the need for vigilance regarding emerging species within the FOSC, particularly F. veterinarium. This highlights the need for improved diagnostic tools and targeted research to combat fusarioid-related infections effectively.

Objectives: Accuracy of diagnostic tests for invasive pulmonary aspergillosis (IPA) using bronchoalveolar lavage fluid (BALF) remains suboptimal. Elevated tissue iron in lung transplant and murine models is linked to invasive Aspergillus growth. This study examines the correlation between BALF iron levels, IPA, and 12-week mortality.

Methods: We conducted a retrospective cohort study at a tertiary care center, including 100 BALF samples from patients with hematological malignancies and suspected IPA between 2014 and 2019. Data regarding iron concentrations, mycological tests, and 12-week mortality were analyzed.

Results: Higher iron levels correlated with a greater likelihood of IPA based on EORTC/MSGERC 2020 definitions (p = 0.038). The ROC area was 0.648 (95% CI 0.531-0.764), with an optimal cut-off of 0.75 µmol/L to distinguish cases (27 probable and 0 proven IPA) from controls (56 possible and 17 no IPA), with sensitivity 76.9% and specificity 47.3%. Iron levels were positively correlated with higher fungal loads (galactomannan: Spearman's ρ 0.323, p = 0.001; Aspergillus PCR Ct-values: ρ - 0.602, p = 0.002). A trend toward higher 12-week mortality was observed in patients with iron concentrations ≥ 0.90 µmol/L compared to lower levels (p = 0.086).

Conclusions: BALF iron concentrations were highest in those with probable IPA, followed by possible IPA and lowest in patients without IPA, with higher iron levels also correlating with fungal loads and potentially with 12-week mortality. However, given the various potential confounding factors, further prospective studies are essential to establish causality. These findings warrant additional investigation into BALF iron as a potential marker for 12-week survival, but validation is necessary before considering it as a supplementary marker in the current EORTC/MSGERC 2020 classification for probable or possible IPA.

Invasive fungal infections pose a significant health threat. Yarrowia lipolytica (formerly known as Candida lipolytica) is an opportunistic yeast with pathogenic potential, but its virulence and impact on the host remain poorly understood. This study aimed to investigate the infection characteristics associated with this relatively unknown pathogen by establishing reliable animal models. We developed intravenous challenge models in immunocompetent and immunosuppressed BALB/c mice by injecting fungal cells directly into the bloodstream. In immunocompetent mice, Y. lipolytica was effectively cleared even at the highest challenge dose of 1 × 10⁸ cells, resulting in minimal mortality. However, this clearance was accompanied by a significant elevation in peripheral blood cytokine levels. Three days post-infection, the fungal burden was highest in the lungs (P < 0.0001), followed by the spleen, kidneys, liver, and brain. In immunosuppressed mice, the mortality rate following Y. lipolytica infection significantly increased (P < 0.001), with the highest fungal burden consistently observed in the lungs. In the immunosuppressed model, clinical isolates exhibited a greater lung fungal burden compared to industrial isolate. In conclusion, Y. lipolytica is a low-virulence fungus that is challenging to establish as a fatal infection in immunocompetent hosts but exhibits a marked tropism for the lungs, where lung fungal burden serves as an effective indicator of virulence. This model may also provide critical insights for studying fungal pulmonary infection pathogenesis and the infection dynamics of Y. lipolytica, especially for immunocompromised patients.

This study presents the first high-quality assembled genome of Naganishia uzbekistanensis, derived from a clinical isolate CY11558 obtained from a patient with a postoperative pulmonary infection. This work provides an improved reference assembly for downstream research and diagnosis of infections caused by this species.

Background: Interdigital tinea pedis is a common type of tinea pedis that occurs between toes and is easy to recur. Recently, the skin microbiome analysis of interdigital tinea pedis showed changes in bacterial microbiome in addition to fungal infection.

Objectives: To investigate the efficacy and safety of clioquinol 3% cream in treating interdigital tinea pedis as well as characterize changes in the skin microbiome during treatment.

Methods: The clinical characteristics and skin microbiome of patients with interdigital tinea pedis were investigated in a longitudinal prospective study. In total 28 participants were rcruited to use the clioquinol 3% cream topically to the target skin lesions twice a day for 1 week. Disease severity evaluation, fungal microscopic examination, and sample collection for skin microbiome analysis were performed at baseline, after treatment, and 1 week post-treatment.

Results: Compared with baseline, the disease severity, lesion score, pruritus score, and malodor score of the patients significantly decreased after treatment and at 1 week post-treatment (P < 0.05). The fungal profiles after treatment and 1 week post-treatment revealed significantly decreased abundance of Trichophyton and significantly increased abundances of Cladosporium, Alternaria, and Aspergillus, which led to higher fungal diversity than pretreatment samples. The bacterial profiles after treatment and 1 week post-treatment revealed significantly decreased abundances of Brevibacterium, Finegoldia, and Facklamia. The abundance of Streptococcus and bacterial diversity were also significantly decreased at 1 week post-treatment. The disease severity was positively associated with the abundance of Trichophyton, Arthroderma, Finegoldia, Facklamia, Brevibacterium, Corynebacterium, and Porphyromonas.

Conclusions: The clioquinol 3% cream was efficient on treating interdigital tinea pedis by decreasing the abundance of pathogenic fungus, recovering the normal balance of the fungal and bacterial communities, and restore species diversity.