Mycoses最新文献

Objectives: This study aimed to evaluate the clinical use of pentraxin 3 serum level as a biomarker for screening episodes of invasive fusariosis among high-risk onco-haematological patients.

Methods: We analysed 63 serum samples from patients with invasive mould diseases and controls, which had been collected between 2009 and 2021 and stored at the Special Mycology Laboratory of Universidade Federal de São Paulo, Brazil. Material included samples from eight patients with invasive fusariosis, nine with invasive aspergillosis, and control groups comprising 20 healthy individuals, eight neutropenic patients with acute myeloid leukaemia, and eight allogeneic haematopoietic stem cell transplant recipients without any concomitant infection, and 10 neutropenic individuals who developed a microbiologically documented gram-negative bacteremia. PTX3 levels were quantified using an enzyme-linked immunosorbent assay (ELISA), and statistical analyses were performed using SPSS Statistics v.28.0, California USA.

Results: The optimal PTX3 detection threshold was established at 10 pg/mL, with the highest levels observed in patients with invasive aspergillosis (5532.8 pg/mL) and invasive fusariosis (3718.1 pg/mL). Healthy controls revealed PTX3 levels ranging from 109.9 to 385.7 pg/mL. Significant differences were noted among all groups (p < 0.001), with PTX3 levels exceeding 1000 pg/mL exclusively in patients with IMDs. Notably, high PTX3 serum levels were detected in four out of the eight samples that had been collected 1-5 days before the diagnosis of fusariosis by culture.

Conclusions: Our results suggest that serum PTX3 quantification holds significant potential for screening patients with suspected invasive fusariosis among onco-haematological patients, similar to its role in invasive aspergillosis.

Background: Antifungal resistance is an expanding and increasingly significant issue representing a global threat for public health. In the last few years, different cases of dermatophytosis infections due to terbinafine-resistant Trichophyton mentagrophytes have been reported worldwide. In particular, T. mentagrophytes genotype VIII, proposed as T. indotineae, represents an emerging pathogen showing increasing spread worldwide that exhibits reduced susceptibility to different antifungal agents.

Objectives: Here, we characterise the genome of a T. indotineae clinical strain (named PG11NEG-TBRES) resistant to terbinafine and fluconazole isolated in the northern part of Italy.

Methods: Whole genome sequencing was performed with the Illumina MiSeq and Oxford Nanopore MinION systems, and hybrid genome assembly was executed with Unicycler. Phylogenomic and copy number analyses were performed by core genome SNPs analysis and coverage depth of mapping reads.

Results: PG11NEG-TBRES belonged to the T. mentagrophytes genotype VIII (known as T. indotineae) and analysis of SQLE gene showed that the PG11NEG-TBRES strain harboured Leu³⁹³Ser. Phylogenomic analysis revealed that PG11NEG-TBRES was clonally related to fluconazole-resistant strains; deep genomic analysis showed the presence of different mutations within ERG4, MDR1 and MFS genes involved in ergosterol biosynthesis and the presence of five copies of tinCYP51b in comparison to susceptible isolates.

Conclusions: Our work highlights the importance of genomic characterisation to define the mechanism related to antifungal resistance and to monitor the spread of emerging dermatophytosis infections.

Background: Diagnosing invasive aspergillosis (IA) remains challenging despite the availability of various tests due to the limited sensitivity and variability in accuracy depending on the clinical context. Laboratory-based definitions consider different mycological criteria, such as culture and galactomannan (GM) positivity, equivalent in diagnostic weight. However, a more detailed analysis is essential for reliably distinguishing true infection from colonisation.

Objectives: This laboratory-based pilot study aimed to evaluate the diagnostic reliability of culture positivity by comparing it with fungal microscopy, GM testing, and Aspergillus-specific PCR in bronchoalveolar lavage fluid (BALF) samples, all of which were culture-positive for Aspergillus.

Materials and methods: Ninety-two Aspergillus fumigatus culture-positive BALF specimens were obtained from mixed patient populations, displaying various risk factors for IA. The multi-assay approach used direct microscopy, GM, and Aspergillus-specific PCR. The diagnostic value of each test was assessed utilising a composite score based on mycological findings and clinical suspicion.

Results: Among 92 culture-positive BALF samples, positivity rates for microscopy, GM, and PCR were 12.0% (n = 11), 27.2% (n = 25), and 28.3% (n = 26), respectively. Notably, in 58.7% (n = 54) of cases, culture positivity was not supported by any other mycological test. Direct microscopy showed the strongest correlation with other diagnostic methods, whereas GM and PCR showed moderate agreement.

Conclusions: Based on our data, the current practice of weighing all mycological parameters equally should be reconsidered, with greater emphasis on microscopy and multimodal diagnostics rather than on culture alone, particularly in non-neutropenic patients.

Background: Surgery is the primary treatment method for non-invasive fungal sinusitis, but challenges include prolonged postoperative inflammation recovery and high recurrence rates. Existing evidence regarding the role of antifungal therapy in enhancing postoperative recovery and reducing recurrence rates in non-invasive fungal sinusitis remains inconclusive. This meta-analysis aimed to systematically evaluate the impact of antifungal therapy on postoperative outcomes in non-invasive fungal sinusitis.

Methods: An eight-database systematic search was performed through March 1, 2025. Primary outcomes included relapse rate and total effective rate, with secondary outcomes consisting of adverse reaction incidence and average epithelialisation time. Subgroup analysis based on antifungal administration routes was also performed.

Results: The antifungal therapy group had significantly lower relapse rates (Odds Ratio [OR] = 0.27, 95% Confidence Interval [CI]: 0.18-0.40, p < 0.00001) and higher total effective rates (OR = 5.41, 95% CI: 3.17-9.23, p < 0.00001) compared to controls. Subgroup analysis showed that topical antifungal therapy (OR = 0.20, 95% CI: 0.12-0.32, p < 0.00001) had a more significant difference in relapse rates than systemic antifungal therapy (OR = 0.54, 95% CI: 0.27-1.05, p = 0.07).

Conclusions: Antifungal therapy after surgery for non-invasive fungal sinusitis, particularly topical antifungal therapy, is beneficial. However, the evidence is limited by the low quality of available studies. Future studies with larger sample sizes, multicentre designs and double-blind randomised controlled trials (RCTs) are necessary to validate these conclusions.

Background: The diagnostic cut-off values for IgG antibodies against recombinant Aspergillus fumigatus (rAsp) antigens in allergic bronchopulmonary aspergillosis (ABPA) remain unclear.

Objectives: To derive and validate diagnostic cut-offs for IgG antibodies against rAsp f 1, f 2 and f 4 in ABPA and assess their diagnostic performance in distinguishing ABPA from asthma.

Methods: In this case-control study, we prospectively enrolled consecutive subjects with asthma and ABPA. We measured serum IgG levels against rAsp f 1, rAsp f 2 and rAsp f 4 using a fluorescent enzyme immunoassay. Subjects were randomly split into derivation (50%) and validation (50%) cohorts. Cut-offs were derived using receiver operating characteristic (ROC) curves and Youden's index. Additionally, we performed Bayesian latent class analysis (BLCA) using two-component Gaussian mixture models to derive unbiased cut-offs. Diagnostic performance was assessed using sensitivity, specificity and the area under the ROC curve (AUROC).

Results: Of 375 participants, 261 had ABPA and 114 had asthma. ROC-derived AUROC values for rAsp f 1, f 2 and f 4-IgG were 0.63, 0.47 and 0.52, while the cut-off values were 10.1 mgA/L, 10.3 mgA/L and 10.5 mgA/L, respectively. Sensitivity was ≤ 42% for all antigens, while specificity exceeded 89%. BLCA yielded cut-offs of 18.6, 14.9 and 13.7 mgA/L for f 1, f 2 and f 4, respectively, with similarly poor sensitivity and high specificity.

Conclusions: IgG antibodies against rAsp f 1, f 2 and f 4 exhibit high specificity but poor sensitivity in identifying ABPA, limiting their utility as standalone diagnostic markers.

Sexually transmitted dermatophyte infections are an emerging public health concern, with increasing incidence reported across multiple countries. These infections are mainly spread through direct skin-to-skin contact during sexual activity and are more commonly found in individuals with high-risk sexual practices. The likelihood of infection is heightened by frequent pubic hair grooming or regular use of shared spaces like gyms and saunas. Clinically, presentations are often severe, widespread and atypical, which may delay diagnosis or lead to misidentification. Accurate species-level identification is critical and increasingly reliant on molecular sequencing techniques, including ITS and tef1α regions, which are also valuable for strain surveillance and contact tracing. Management strategies should emphasise systemic antifungal therapy, with consideration for adjunctive topical agents or antibiotics in cases of secondary infection. Individualised treatment plans may require extended therapy durations or combination regimens to ensure clinical resolution. In addition to pharmacologic intervention, education on hygiene practices, risk of reinfection and the importance of environmental decontamination and follow-up care is essential for preventing recurrence and curbing transmission.

Background: The differential diagnosis of invasive pulmonary aspergillosis (IPA), pulmonary mucormycosis (PM), bacterial pneumonia (BP) and pulmonary tuberculosis (PTB) are challenging due to overlapping clinical and imaging features. Manual CT lesion segmentation is time-consuming, deep-learning (DL)-based segmentation models offer a promising solution, yet disease-specific models for these infections remain underexplored.

Objectives: We aimed to develop and validate dedicated CT segmentation models for IPA, PM, BP and PTB to enhance diagnostic accuracy. Methods：Retrospective multi-centre data (115 IPA, 53 PM, 130 BP, 125 PTB) were used for training/internal validation, with 21 IPA, 8PM, 30 BP and 31 PTB cases for external validation. Expert-annotated lesions served as ground truth. An improved 3D U-Net architecture was employed for segmentation, with preprocessing steps including normalisations, cropping and data augmentation. Performance was evaluated using Dice coefficients. Results：Internal validation achieved Dice scores of 78.83% (IPA), 93.38% (PM), 80.12% (BP) and 90.47% (PTB). External validation showed slightly reduced but robust performance: 75.09% (IPA), 77.53% (PM), 67.40% (BP) and 80.07% (PTB). The PM model demonstrated exceptional generalisability, scoring 83.41% on IPA data. Cross-validation revealed mutual applicability, with IPA/PTB models achieving > 75% Dice for each other's lesions. BP segmentation showed lower but clinically acceptable performance ( ＞72%), likely due to complex radiological patterns.

Conclusions: Disease-specific DL segmentation models exhibited high accuracy, particularly for PM and PTB. While IPA and BP models require refinement, all demonstrated cross-disease utility, suggesting immediate clinical value for preliminary lesion annotation. Future efforts should enhance datasets and optimise models for intricate cases.

Introduction: Fungaemia due to non-Candida and non-Cryptococcus yeasts is uncommon but clinically significant, particularly in immunocompromised hosts. We aimed to describe the epidemiology, microbiology and outcomes of bloodstream infections (BSIs) caused by these organisms.

Methods: We identified all BSIs due to non-Candida and non-Cryptococcus yeasts over a 20-year period using statewide laboratory and administrative health databases.

Results: Seventy-five unique episodes were identified. The most frequent genera were Trichosporon (n = 31, 41.3%), Rhodotorula (n = 26 34.7%) and Saccharomyces (n = 10, 13.3%) species. Antifungal susceptibility testing performed in 33 (44%) episodes revealed high MICs (> 16 mg/L) to echinocandins for Trichosporon and Rhodotorula species. Fluconazole MICs were universally elevated ( $\ge$  32 mg/L) in Rhodotorula spp. but lower in Saccharomyces cerevisiae (2-4 mg/L). Voriconazole and posaconazole had good in vitro activity across all genera where tested. Thirty-day mortality was 22.7%, with the highest rate observed in S. cerevisiae (50.0%). Mortality was associated with malignancy (aHR 4.71, 95% CI 1.00-22.25), heart failure (aHR 11.31, 95% CI 1.66-77.14) and intensive care unit (ICU) admission (aHR 7.05, 95% CI 0.99-50.36). The presence of a central line may be protective (aHR 0.17, 95% CI 0.03-1.04). Rhodotorula infection was associated with lower mortality on univariable analysis (HR 0.11, 95% CI 0.14-0.86) compared with Trichosporon species.

Conclusion: Although rare, fungaemia due to non-Candida and non-Cryptococcus yeasts is associated with significant mortality and antifungal resistance. Species identification and susceptibility testing are crucial to guide treatment. Increased awareness is essential in high-risk patients, particularly those with malignancy, heart failure, or requiring ICU admission.

Background: Cryptococcus bloodstream infections (BSIs) or cryptococcaemia are severe opportunistic infections with high mortality, predominantly affecting immunocompromised individuals or those with end-stage organ disease. Population-based studies examining infection trends and associations between host factors, geography, antifungal resistance, and clinical outcomes are few.

Methods: Blood cultures with growth of Cryptococcus species were retrospectively identified over a 20-year period (January 1, 2000-December 31, 2019) from a state-wide database. Clinical, microbiological and outcome information was also obtained. Survival analyses were used to establish associations between clinical or microbiological characteristics and mortality.

Results: A total of 118 cryptococcaemia episodes (115 patients) were identified, with Cryptococcus neoformans complex causing 98 episodes (83.1%). HIV-associated infections represented 28 episodes (23.7%), with non-HIV episodes (n = 90) more likely to be associated with comorbidities including solid organ transplantation, malignancy, chronic kidney disease, and rheumatological conditions. Overall, 30-day all-cause mortality was 34%, with higher mortality in non-HIV-associated cases (41.7% vs. 12.5%, HR 0.29; 95% CI 0.09-0.94). Of C. neoformans complex isolates with a fluconazole MIC $\ge$ 8 mg/L, 6 (46%) were observed in the most recent 5-year period. Thirty-day (p = 0.85) and 1-year (p = 0.35) mortality increased in a stepwise fashion with increasing fluconazole MIC values in C. neoformans complex infection. Fifty-three episodes (49.1%) documented isolated cryptococcaemia. Patients with additional sites of infection, including CNS involvement, experienced longer hospital stays. Those living in a regional or remote area (HR 1.33; 95% CI 0.68-2.61) or with older age (HR 1.02; 95% CI 1.00-1.04) experienced higher rates of death, although these findings were not statistically significant.

Conclusion: Cryptococcus BSI is a highly lethal condition, particularly among non-HIV infected individuals. We highlight the prognostic importance of blood culture collection in patients with suspected cryptococcal infection. Identifying contemporary risk factors for mortality is critical to understanding what drives poor outcomes. There is a need for continued surveillance of fluconazole susceptibility among Cryptococcus species.