Mycoses最新文献

Introduction: Candidaemia is a life-threatening infection with a persistently high mortality rate, despite significant advances in antifungal therapy and supportive care. The European Confederation of Medical Mycology developed the EQUAL Candida Score as a standardised tool to evaluate adherence to guideline-based management; however, its prognostic value has not been consistently demonstrated in different patient populations. This study aimed to evaluate the clinical impact of adhering to guidelines and determine the predictive value of the EQUAL Candida Score for mortality risk in candidaemia patients.

Methods: This retrospective cohort study included adult patients with candidaemia who were treated at a tertiary care hospital. Patients were classified as survivors or nonsurvivors based on 90-day candidaemia-related mortality. We identified independent predictors of mortality using multivariable Cox regression analysis and subsequently developed a prognostic nomogram based on the final model.

Results: A total of 189 patients with candidaemia were included in the study, of whom 88 (46.6%) died within 90 days. The median EQUAL Candida Score was significantly lower among nonsurvivors compared with survivors (8 vs. 13, p < 0.001). This prognostic association remained consistent in subgroup analyses, both in patients with (10 vs. 13, p < 0.001) and without (10 vs. 13, p = 0.022) central venous catheters. An optimal cut-off score of 12 was identified across all groups, yielding a sensitivity of 70%-80% and a specificity of 79%. Kaplan-Meier survival analysis further confirmed that patients with an EQUAL Score ≥ 12 had significantly higher survival rates in all subgroups. In multivariable Cox regression, immunosuppressive treatment (HR 1.728), septic shock (HR 2.035), lack of source control (HR 2.013) and an EQUAL Score < 12 (HR 3.503) were identified as independent predictors of candidaemia-related mortality. Based on these variables, a nomogram was developed to estimate individualised survival probabilities at 1, 3 and 6 months. External validation in an independent cohort (n = 64) confirmed the model's prognostic performance, with a Harrell's C-index of 0.704 (95% CI: 0.587-0.821), despite the limited sample size.

Conclusion: The EQUAL Candida Score serves as a reliable prognostic marker for candidaemia. When combined with clinical parameters, it enhances the accuracy of mortality risk estimation. Our novel nomogram provides a practical framework for early risk stratification and may optimise management strategies for high-risk patients.

Background: Tinea pedis is a type of dermatophytosis that affects the superficial layers of the skin on feet. Limited data are available on the skin microbiome composition in affected patients and its changes following topical antifungal therapy.

Objectives: To evaluate the clinical and microbiological effects of topical ketoconazole 2% cream (KTZ) and miconazole nitrate 2% cream (MCZ) using standardised clinical scoring and amplicon sequencing.

Methods: A total of 42 patients with tinea pedis and 28 healthy controls were enrolled. Skin swabs were collected from lesional sites (interdigital or heel) at baseline, after 4 weeks of treatment, and 2 weeks post-treatment. DNA was extracted from the samples, and the bacterial 16S rRNA (V3-V4 region) and fungal ITS1-5F regions were sequenced to analyse microbial community composition.

Results: Both KTZ and MCZ led to comparable clinical improvement. However, the KTZ group showed faster symptom resolution and a higher sustained improvement rate during follow-up. Treatment with either antifungal effectively reduced the abundance of pathogenic Trichophyton species to levels similar to those in healthy controls, thereby contributing to partial recovery of the overall fungal community structure. In parallel, the bacterial profile became more dispersed, with notable shifts observed in bacterial genera such as Staphylococcus and Corynebacterium following treatment.

Conclusion: Topical antifungal therapy with KTZ or MCZ effectively improved the symptoms of tinea pedis, diminished the pathogenic fungal load and altered both fungal and bacterial community compositions. However, only partial restoration of the mycobiome was achieved, and the bacterial profile, especially in the interdigital region, showed a lack of bacterial normalisation. These findings highlight the need for further studies to assess long-term outcomes and to explore microbiome-targeted strategies addressing both bacterial and fungal components.

Background: Rezafungin, a novel echinocandin with once-weekly intravenous dosing, offers potential advantages for outpatient parenteral antifungal therapy (OPAT) in invasive candidiasis (IC). While clinical trial data support its efficacy and safety, real-world experience remains limited.

Methods: A retrospective analysis of patients treated with rezafungin across Germany, Italy, Spain, and the United States between January 2024 and June 2025 was conducted. Data was collected via the FungiScope registry. Clinical characteristics, indications for rezafungin, outcomes, safety, and logistical aspects of administration were evaluated.

Results: Fifteen patients were included, fourteen with IC; one with chronic pulmonary aspergillosis. Regarding patients with IC, the median age was 65.5 years; 43% were female. The most frequently identified pathogens were Candida glabrata (57%) and Candida parapsilosis (21%). Primary indications for rezafungin were intravascular (36%) and osteoarticular infections (36%). Rezafungin was mainly selected to enable OPAT (86%) or due to fluconazole resistance (36%) or drug-drug interactions (14%). The median treatment duration was 9 weeks (range: 1-38 weeks). One mild adverse event occurred (cutaneous photosensitivity), but rezafungin was otherwise well tolerated. Complete clinical or mycological response was observed in 36% at day 30, and partial response in 50% of patients. Access differed substantially across centres due to administrative and reimbursement hurdles, affecting treatment transition to rezafungin in 71% of patients with IC.

Conclusions: Rezafungin was effective and well tolerated in this cohort, particularly in patients requiring long-term treatment. Administrative and logistical hurdles remain significant barriers to its widespread use. Facilitated access and enhanced awareness may improve patient outcomes by supporting early initiation and continuity of care.

Background: Mucormycosis is a rare, rapidly progressive fungal infection with a high mortality rate. However, clinical data of mucormycosis patients, especially those related to adverse outcomes in China, remain limited.

Objective: To enhance understanding of the clinical characteristics of different infection site mucormycosis and identify the factors associated with adverse outcomes.

Methods: A 14-year retrospective study was conducted at a tertiary care hospital in China. Patients were categorised based on the site of infection and clinical outcomes.

Results: From 2010 to 2024, 32 cases of mucormycosis were identified. Among these, pulmonary mucormycosis (PM) was the most common infection site, followed by disseminated mucormycosis. All patients had underlying comorbidities, predominantly chronic lung disease (37.5%) and diabetes mellitus (34.3%). All received pharmacological treatment, most commonly amphotericin B; 15.6% of patients additionally underwent surgical intervention. Chest CT findings in PM cases most frequently revealed bilateral involvement (68.8%) and cavitation (43.8%). Diagnosis was primarily based on metagenomic next-generation sequencing (mNGS, n = 14) and histopathological examination (n = 11). Adverse outcomes were observed in 46.9% of patients and were significantly associated with corticosteroid or immunosuppressant use, COVID-19 co-infection, disseminated disease, thrombocytopenia, hypoalbuminemia, elevated aspartate aminotransferase (AST), increased incidence of complications, and ICU admission (all p < 0.05).

Conclusion: Pulmonary mucormycosis was the predominant subtype in this cohort and was frequently associated with chronic lung disease and diabetes. The high incidence of adverse outcomes highlights the necessity for early diagnosis, prompt antifungal therapy, and aggressive management of complications to improve patient survival.

Background: Starting from 2018 onwards, several outbreaks of fluconazole-resistant C. parapsilosis have been reported in many countries worldwide.

Objectives: Here we report a retrospective study on C. parapsilosis blood isolates collected over 7 years (2018-2024) in two hospitals in Northern Italy.

Patients/methods: The study involved 169 C. parapsilosis isolates collected from individual hospitalised patients. We assessed the antifungal susceptibility of the isolates, evaluated the presence of mutations in the ERG11 gene and performed multilocus microsatellite typing to highlight the genetic relatedness of the strains. All isolates were also tested for their ability to produce biofilm.

Results: Among the 169 clinical isolates, 124 (73.4%) were classified as fluconazole-resistant C. parapsilosis (FRCP) and 45 (26.6%) as fluconazole-susceptible (FSCP). ERG11 sequencing highlighted that the most frequent mutation in FRCP is the Y132F (118/124, 95.2%). None of the FSCP carried the Y132F. Microsatellite genotyping showed five major clusters and 13 sub-clusters, formed by isolates sharing identical genotypes. Sub-cluster R1 included 96 FRCP carrying the Y132F substitution, isolated from 2018 to 2024 in both hospitals. Interestingly, 99.1% of the FRCP carrying the Y132F mutation were categorised as low biofilm formers, while FRCP carrying other ERG11 mutations were categorised as medium or high biofilm formers.

Conclusions: Our results confirmed that Y132F may be mainly responsible for azole resistance in C. parapsilosis and inter-hospital spread. As we found, recent clinical studies indicate that FRCP isolates responsible for severe outbreaks produce thin biofilms. Mutated and therefore resistant strains may exhibit reduced biofilm production as a protective mechanism.

Background: Chronic pulmonary aspergillosis (CPA) is most commonly caused by Aspergillus fumigatus (AF-CPA). Serum A. fumigatus-IgG, a pivotal investigation for diagnosing CPA, misses 10%-15% of CPA cases. We aimed to determine whether measuring serum IgG against non-fumigatus Aspergillus species enhances the serodiagnosis of CPA.

Methods: We prospectively enrolled consecutive, treatment-naïve adults with CPA. The diagnosis of CPA was made using the ESCMID-ERS criteria. Serum IgG against Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger and Aspergillus terreus (cut-off, 27 mgA/L) was measured by fluorescent enzyme immunoassay. Non-fumigatus-CPA (NF-CPA) was defined when non-fumigatus species-specific IgG titres exceeded A. fumigatus-IgG by ≥ 25%. The primary objective was to evaluate the incremental diagnostic yield of non-fumigatus species-specific IgG for identifying CPA cases missed by A. fumigatus-IgG. The secondary outcome was to compare clinical features and treatment outcomes of AF-CPA and NF-CPA.

Results: Among 279 patients (mean age 45.7 ± 14.8 years, 64% male), seropositivity was 95.3% for A. fumigatus, 70.6% for A. flavus, 56.6% for A. niger and 30.5% for A. terreus. The addition of non-fumigatus-IgG increased serologic yield by 61%. NF-CPA was diagnosed in 14% (39/279), with A. fumigatus-IgG alone missing 25.6% of these cases. Treatment outcomes at six (n = 228) and 12 (n = 222) months were similar between AF-CPA and NF-CPA groups, although the percentage reduction in serum A. fumigatus-IgG was significantly greater in AF-CPA.

Conclusions: Incorporating non-fumigatus Aspergillus-IgG enhances the serodiagnosis of CPA. However, treatment outcomes are similar in patients with AF-CPA and NF-CPA.

Background: In the United States, aspergillosis and mucormycosis are associated with substantial healthcare costs and mortality. Recent nationally representative data about hospitalisations for these infections are limited, though several reports specifically describe increases in COVID-19-associated aspergillosis and mucormycosis, likely because of critical illness-related immune dysregulation and treatments involving systemic corticosteroids.

Objectives: To update disease burden estimates, we describe trends in aspergillosis-related and mucormycosis-related hospitalisations (A-RH and M-RH).

Methods: We used the 2016-2021 Healthcare Cost and Utilisation Project National Inpatient Sample and U.S. Census Bureau data to calculate A-RH and M-RH rates, examining annual trends, overall and stratified by demographic characteristics. We examined A-RHs and M-RHs during 2020-2021, comparing features and in-hospital mortality for those with vs. without COVID-19.

Results: During 2016-2021, an estimated 86,570 A-RHs occurred, with rates (per 1,000,000 population) stable from 2016 to 2019 (range: 42.3-44.5) and increasing from 40.1 (2020) to 51.5 (2021). An estimated 8565 M-RHs occurred, with rates increasing from 3.8 to 5.8. During 2020-2021, 6025/24,285 (24.8%) of A-RHs and 420/2920 (14.4%) of M-RHs were COVID-19-associated. A-RHs and M-RHs involving COVID-19 had mortality rates exceeding 50%, which was ≈3 to 4-fold higher than those for A-RHs and M-RHs without COVID-19.

Conclusion: Rates of A-RHs and M-RHs in the United States peaked in 2021, likely reflecting the increased burden of COVID-19 in 2021 compared with 2020. Ongoing monitoring of risk factors and clinician awareness is essential for managing and preventing these infections.

Objectives: Computed tomography (CT) plays a critical role in the early detection and diagnosis of pulmonary invasive mould infection. This study aimed to compare the CT findings of proven invasive pulmonary aspergillosis (IPA) and proven pulmonary mucormycosis (PM) and develop a clinical scoring system based on CT features to differentiate PM from IPA.

Methods: The medical records of the pathology database among adult patients (aged ≥ 18 years) diagnosed with proven IPA or PM between January 2003 and June 2024 were retrospectively reviewed, according to the 2020 European Organisation for Research and Treatment of Cancer criteria. CT scans were reviewed by an experienced radiologist. The primary outcome was CT findings in PM and IPA. We investigated and compared the thoracic CT findings between PM and IPA to identify the predictors of PM compared to IPA prior to invasive diagnostic procedures.

Results: A total of 94 patients were included (60 with IPA and 34 with PM). The most common underlying conditions were malignancy (53.2%) and transplantation (47.9%). In univariable analysis, CT features significantly associated with PM, compared to IPA (p < 0.05), included representative lesion size ≥ 4 cm (odds ratio [OR] 3.61, 95% CI 1.48-8.79), consolidation (OR 5.56, 95% CI 1.52-20.38), halo sign (OR 3.33, 95% CI 1.39-8.02), reverse halo sign (RHS) (OR 6.73, 95% CI 2.39-18.98) and airway-invasive lesion (OR 0.32, 95% CI 0.13-0.78). In multivariate analysis, representative lesion size ≥ 4 cm, RHS, and airway-invasive lesion were identified as independent predictors of PM, compared to IPA. These three factors were incorporated into a point-based scoring system (representative lesion size ≥ 4 cm = 11 points; RHS = score 17 points; airway-invasive lesion = -12 points). A total score of > 8 differentiated PM from IPA with 70.6% sensitivity and 78.3% specificity.

Conclusions: CT findings of large consolidative lesions, the presence of a reverse halo sign, and the absence of airway invasion may aid in the early differentiation of PM from IPA.

Background: Although several fungal infections have been linked to asthma development, the relationship between histoplasmosis and asthma development has not been fully described.

Objectives: To assess the incidence of new asthma diagnosis codes or short-acting β₂ agonist (SABA) prescription in the year following histoplasmosis diagnosis and identify potentially related factors.

Methods: We used a large health insurance claims database to identify patients with histoplasmosis with and without an asthma diagnosis code or a short-acting β₂ agonist prescription in the year after diagnosis.

Results: Among 1819 patients diagnosed with histoplasmosis, 252 (13.9%) received a new asthma diagnosis or SABA prescription in the subsequent year, more than double the proportion in the general population (5.8%). Pulmonary histoplasmosis and symptoms such as dyspnea and wheezing were associated with asthma diagnosis or SABA receipt.

Conclusion: These findings suggest that histoplasmosis may predispose certain patients to airway hyperreactivity, particularly those with acute pulmonary symptoms. Further research is needed to elucidate potential mechanisms underlying these findings, which could inform strategies to mitigate post-infectious airway disease in affected patients.

Background: Geophilic Nannizzia dermatophytes are increasingly implicated in stubborn skin, hair, and nail infections, yet MALDI-TOF MS evaluations and antifungal-susceptibility data have focused almost exclusively on N. gypsea. Biochemical profiles and MICs cut-offs are limited.

Objectives: To benchmark two commercial MALDI-TOF MS libraries and to determine in vitro activity of eight antifungals against a genus-wide panel of Nannizzia species.

Methods: One-hundred-and-three ITS-confirmed isolates representing 12 species were grown on potato-dextrose agar (PDA) for 7-14 days. Spectra were acquired with (i) the MSI-2 Dermatophyte Library after 4-14 days' PDA incubation (100 cultures) and (ii) the Bruker MALDI Biotyper Filamentous-Fungi Library 6.0/2023 after ≤ 3 days' growth in Sabouraud-dextrose broth (SDB) (73 cultures). BCCM/IHEM strains could not be evaluated on the Biotyper because of licence restrictions, leaving 73 non-duplicate isolates for direct MSI-2 vs MBT comparison. EUCAST E.Def 11.0 micro-broth dilution determined MICs for eight agents.

Results: MSI-2 achieved its highest accuracy with PDA day-7 cultures (45/73, 62%), whereas the liquid Biotyper protocol yielded 49/73 correct identifications (67%) within four days. Accepting low-confidence scores (≥ 1.7) from either library increased overall accuracy to 73%. MSI-2 remained superior for N. gypsea (73%) and uniquely detected N. nana (50%), which is absent from the current Biotyper release. Conversely, the Biotyper outperformed MSI-2 for N. incurvata, N. fulva, and N. praecox. Six very rare species (N. lorica, N. aenigmatica, N. corniculata, N. duboisii, N. perplicata, N. polymorpha) were not recognised by either database. Terbinafine displayed the lowest geometric mean MIC (0.009 mg/L); fluconazole and griseofulvin showed the highest values, and one US N. fulva isolate exhibited elevated itraconazole/voriconazole MICs (1 mg/L).

Conclusions: Diagnostic coverage of Nannizzia remains incomplete. Expanding commercial MALDI-ToF MS libraries with spectra from rare species and performing routine susceptibility testing are essential to optimise patient management.