Mycoses最新文献

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.

Background: β-D-Glucan (BDG) is a useful but nonspecific biomarker in patients with suspected invasive fungal diseases including Pneumocystis pneumonia. Little is known, however, about its utility for response monitoring in chronic disseminated candidiasis (CDC).

Patients and methods: We describe the utility and pitfalls of serum BDG in paediatric cancer patients with suspected CDC. BDG in serum was measured serially (i.e., 5 to 10 times of a time period of 200 to 400 days) by a commercially available assay (Fungitell; Associates of Cape Cod, MA, USA) and values were correlated to patient- and disease-related variables.

Results: Five paediatric patients (4f/1 m; 4-18 years) with acute lymphoblastic leukaemia (n = 4) and Ewing sarcoma (n = 1) followed between 2013 and 2024 were included. CDC was located in the spleen (n = 5), liver (n = 4), lungs (n = 3), CNS (n = 2), kidney (n = 1), and skin (n = 1); and diagnosed based on imaging, a positive blood culture (n = 1), a positive BDG assay in serum (n = 5), and absence of other etiologies. Patients received IV liposomal amphotericin B and/or caspofungin, followed by fluconazole orally for 184 to > 365 days, respectively. BDG concentrations in serum (35 time points) stayed elevated for prolonged periods of time, were independent of clinical symptoms, and returned to normal with resolution of imaging findings in the four leukaemia patients. In the patient with Ewing sarcoma, liver biopsy performed 5 months after diagnosis due to lack of improvement revealed disseminated aspergillosis.

Conclusions: BDG in serum is useful for microbiological diagnosis and monitoring of probable CDC; however, it remains a non-specific fungal biomarker whose results need to be scrutinised in patients who do not respond to treatment as expected.

Introduction: Onychomycosis remains a challenging condition due to varying cure rates and the risk of recurrence. Topical 40% urea has been proposed as an adjuvant to antifungals to enhance efficacy. Many trials have been done, presenting mixed results.

Methods: Four databases (PubMed, Web of Science, Scopus, and EBSCO), two registers (Cochrane), and grey literature sources were used to identify randomised controlled trials (RCTs) and non-randomised studies (NRSs) published until February 2025. Cure rates (clinical, mycological, and total) were analysed in the meta-analysis, analysing cure rates and comparing urea as an adjuvant to antifungal therapy with antifungals alone. We independently selected eligible articles and extracted relevant data before assessing the quality of the studies. A summary of the findings table was made with GRADEpro GDT using the results of the meta-analyses.

Results: Based on six RCTs and six NRSs involving 424 participants treated with antifungals plus topical 40% urea-130 of which were compared to 129 participants who received antifungals without urea- we found that adding topical 40% urea as an adjuvant significantly improved the clinical cure rate compared to therapy using antifungals alone (OR: 2.05, 95% CI: 1.03-4.11, p < 0.05). However, there were no significant differences in mycological and total cure rates (OR: 1.71; 95% CI: 0.63-4.61; p > 0.25 and OR 1.23; 95% CI: 0.47-3.23; p > 0.5). The reported adverse effects were localised.

Conclusions: Topical 40% urea can be used to improve the clinical efficacy of antifungals for onychomycosis. However, evidence for mycological and total efficacy is lacking. Thus, more rigorous trials are needed to confirm its efficacy and safety.

Protocol registration: PROSPERO-CRD42025638277.

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.