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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.

Background: Although several drugs have been linked to candidiasis, the risk profiles of this condition remain unclear for most therapeutic agents.

Objectives: Aiming to provide critical references for developing clinically actionable risk stratification frameworks, this study investigated risk factors associated with the occurrence and mortality of drug-related candidiasis using real-world data.

Methods: Reporting odds ratios (ROR) were calculated to evaluate the signal strength of candidiasis across drugs reported in the FDA Adverse Event Reporting System (FAERS; Q1 2004 to Q3 2024). Multidimensional regression analyses were conducted to identify key risk factors for drug-related candidiasis.

Results: This pharmacovigilance study identified 259 drugs associated with candidiasis through disproportionality analysis. After exclusion through univariate regression and LASSO regression, the final multivariable logistic regression analysis included 1526 candidiasis cases and 200,173 non-cases (control), revealing that female gender, older age (≥ 65 years) and 32 specific drugs were independent risk factors for drug-related candidiasis. These drugs primarily included monoclonal antibodies (6/32), antibiotics (4/32), glucocorticoids (4/32) and chemotherapy agents (4/32). Affected patients exhibited distinct clinical outcomes, with mortality-related regression analysis further revealing a significant association for these drug classes. Notably, five drugs, cytarabine, etoposide, prednisone, prednisolone and dexamethasone, exhibited dual associations as both independent susceptibility factors and mortality risk factors in drug-candidiasis progression. Our temporal analysis suggested enhanced clinical vigilance during the first month following the administration of these drugs to facilitate early infection detection.

Conclusion: The findings offer critical references for developing risk stratification frameworks in clinical practice, and establish priority targets for future research into the pathogenesis and mortality mechanisms of this infection.

The incidence of invasive fungal diseases has witnessed a significant increase in recent years, presenting a major threat to global public health. Nevertheless, research on fungi lags behind that on bacteria, and the understanding of how fungi cause infections in humans remains limited. Fungi are highly diverse and play a crucial role in natural ecosystems. In this review, we analysed the causes of the increase in human invasive fungal diseases from the perspectives of environmental changes, plant factors, animal factors, soil alterations, human activities and fungal resistance from the viewpoint of One Health, aiming to better understand fungi, adapt to nature and collaborate in multiple fields to reduce human invasive fungal diseases.

Background: Until 2020, azole resistance in Aspergillus fumigatus complex isolates in New Zealand was due to cyp51A hot spot mutations. This report details the appearance of environment-linked tandem repeat (TR)-related azole resistance genotypes since 2021.

Methods: Isolates were tested by broth micro-dilution. Clinical Laboratory Standards Institute criteria were used to define wild type (WT) and non-wild type (non-WT) isolates, which were identified by ß-tubulin gene sequencing and had their cyp51A genotype for azole resistance determined. Whole genome sequencing (WGS) was applied to two patient pairs of sequential WT and non-WT isolates.

Results: From January 2021 to June 2024, 15 of 147 (10.2%) A. fumigatus complex isolates were resistant or non-WT for one or more azole agents. Genotyping detected hot spot mutations in four and TR-associated resistance in nine. No mutations were detected in two isolates. Four of the five TR₄₆ mutations were TR₄₆/Y121F/T289A. Three of the four TR₃₄ mutations were different. WGS of the paired isolates showed that the non-WT isolates were distinct. Azole-containing fungicides are available for home use from garden centres. Patients with TR-associated resistance did not have any obvious exposure to azole-containing fungicides. There was no evidence for healthcare-acquired transmission.

Conclusions: A. fumigatus sensu stricto isolates with TR-mutations linked to environmental resistance are now present in New Zealand. Those at risk of invasive A. fumigatus infection should receive advice to avoid high-risk exposures. Reintroducing monitoring of azole-containing fungicides is recommended.

Background and objective: Trichophyton indotineae is a globally emerging, frequently antifungal-resistant fungus causing severe dermatophytosis. To inform prevention efforts, we analysed the genomic epidemiology and resistance to terbinafine (first-line oral antifungal) from a collection of multinational T. indotineae isolates collected from patients with clinically suspected dermatophytosis during 2016-2023.

Methods: We performed whole genome sequencing and phylogenetic tree analysis based on single-nucleotide polymorphisms (SNPs). T. indotineae phylogenetic results were correlated with patient demographic characteristics and isolate terbinafine susceptibility profiles that were determined by antifungal susceptibility testing and squalene epoxidase gene sequencing. Trichophyton mentagrophytes and Trichophyton interdigitale isolates from the USA, and Trichophyton rubrum isolates from three countries were added for contextual analysis.

Results: Among 347 T. indotineae isolates, 227 (65%) were in vitro resistant to terbinafine. Countries represented were India (43%); Germany (21%); Bangladesh (8%); United States (8%); United Arab Emirates (7%); Iraq (5%); Finland (3%); Poland (2%); Austria, Canada, Cambodia, Estonia, Singapore, and Switzerland (each < 1%). Median SNP difference between isolates was 106 SNPs (range: 0-392). Clustering by age, sex, or country was not observed. One subcluster was composed of terbinafine-resistant isolates with a specific squalene epoxidase gene mutation (F397L) and was widely dispersed among 10 countries. Intra-species genomic diversity was greater among 19 T. rubrum isolates (260 SNPs [range: 73-1038]), or among 10 T. mentagrophytes/T. interdigitale isolates from the USA compared with the intra-species diversity of the T. indotineae isolates.

Conclusions: Our findings corroborate T. indotineae's recent emergence and ongoing international transmission and suggest the rapid spread of a subset of terbinafine-resistant isolates. Continued efforts are necessary to mitigate this pathogen's spread.