Mycopathologia最新文献

Background and aims: Invasive cutaneous fungal infections (ICFIs) are life-threatening complications in pediatric cancer patients. This study aimed to investigate the prevalence, clinical characteristics, and outcomes of ICFIs among pediatric cancer patients hospitalized at a referral oncology teaching Hospital in Shiraz, Iran.

Methods: This cross-sectional study included pediatric patients with malignancies and suspected ICFIs who were admitted to the Amir Oncology Teaching Hospital between 2015 and 2022. Diagnosis was based on the EORTC/MSG criteria and confirmed using clinical, microbiological, and histopathological methods. Data were analyzed using descriptive statistics, Kaplan-Meier survival analysis, and comparative tests, with a significance threshold of p < 0.05.

Results: Among the 24 patients, 58.3% were boys, and 45.8% were aged 1-5 years. Acute lymphoblastic leukemia was the most common malignancy (27.3%). Mucoralean fungi (36.4%) and Aspergillus (59.1%) were the most common. The overall survival rate was 54.2%. Proven ICFIs had the poorest outcomes, with a survival probability declining to zero by month 26. Patients with lower CRP levels and febrile neutropenia had better outcomes (p < 0.001 and p = 0.041, respectively), but survival rates did not vary significantly according to sex, age, or treatment approach (monotherapy versus combination therapy).

Conclusion: In pediatric oncology patients, ICFIs are associated with high mortality, particularly in cases of mucormycosis or proven infections. Improving survival depends on early diagnosis, risk stratification, and rapid management, particularly in patients with neutropenia and fever.

The whole-genome sequencing of two Candida auris isolates from the skin lesions of a Korean head and neck atopic dermatitis patient classified them within clade II. The isolates were susceptible to common antifungals. This study provides valuable genomic data for understanding the epidemiology and antifungal response of this emerging pathogen.

Background: Candidemia is a severe systemic infection with a high mortality risk. While β-D-glucan (BDG) serves as a diagnostic biomarker, its prognostic value in candidemia, particularly in association with Candida bundle compliance, remains unclear.

Methods: In this retrospective multicenter cohort study, we evaluated 96 patients with candidemia across nine Japanese hospitals between 2016 and 2023. Candida bundle compliance was assessed using five key components: central venous catheter removal within 24 h of diagnosis, appropriate initial antifungal therapy, ophthalmologic examination, follow-up blood cultures until clearance, and antifungal therapy for at least two weeks post-clearance. Analyses stratified patients by serum BDG status (positive/negative) and compliance with the Candida bundle (high: 4-5 points; low: 0-3 points). The primary outcome was 30-day mortality, and the secondary outcome was defined as endophthalmitis incidence.

Results: Of 96 eligible patients with candidemia, 70 (72.9%) were BDG-positive and 26 (27.1%) were BDG-negative. The overall 30-day mortality was 17.7%. Among BDG-positive patients, 15 (21.4%) died, while 2 (7.7%) died in BDG-negative cohorts (p = 0.09). Serum BDG positivity demonstrated a statistically significant association with decreased survival rates in the low bundle adherence group (p = 0.02), whereas this correlation was not observed among patients in the high-compliance cohort (p = 0.66). Endophthalmitis occurred in 25.0% of patients, without significant correlation to serum BDG status. C. albicans was associated with a significantly higher incidence of endophthalmitis compared with non-albicans species (45.7% vs. 8.9%).

Conclusions: Serum BDG positivity potentially correlates with worse survival in candidemia, particularly in patients with low bundle compliance. This emphasizes the importance of adherence to standardized Candida management protocols for optimizing patient outcomes.

Background: The utility of polymerase chain reaction (PCR) for diagnosing mucormycosis is uncertain. We conducted a diagnostic test accuracy meta-analysis to determine the performance of Mucorales PCR.

Methods: We systematically reviewed PubMed, Embase, and Cochrane Central databases to identify studies reporting Mucorales PCR (blood or bronchoalveolar lavage fluid [BALF] samples) in at least 10 suspected mucormycosis cases. We pooled sensitivity and specificity using Bayesian (weak and two informative priors) and frequentist methods. Subgroup analyses included middle vs. high-income countries, risk factors (hematological diseases vs. others), study design, assay type (commercial vs. in-house), and testing protocol (serial testing vs. single-time PCR). We assessed the effect of the number of blood tests performed per participant on sensitivity using multivariable meta-regression.

Results: We identified 1524 citations, of which 36 studies (41 datasets, n = 6627 participants; 16,613 samples) were included. The pooled sensitivity and specificity (with 95% credible interval) by Bayesian weak priors (primary analysis) were 51% (34-67%) and 97% (95-98%) for blood; 64% (50-76%) and 97% (95-98%) for BALF samples. We found wide variation in sensitivity, with a 14% increment for every additional blood sample tested per patient. Studies from middle-income countries reported a significantly lower pooled sensitivity (31 vs. 68%) in blood samples and lower specificity in BALF (72 vs. 98%) than high-income countries. No other subgroups showed significant differences.

Conclusion: Mucorales PCR was highly specific but poorly sensitive in blood, and moderately sensitive with high specificity in BALF. Before routine implementation, further well-designed studies from diverse settings and underrepresented regions are needed.

Background: Mucormycosis is a rare, destructive, and life-threatening angio-invasive fungal infection caused by fungi of the order Mucorales. This study highlights the urgent need for more extensive research in this regard. We aimed to assess the epidemiology of mucormycosis at eight tertiary-care centers in Iran over ten years (2010-2020).

Methods: In the current retrospective study, eligible patients were included based on positive histopathology and direct microscopy by potassium hydroxide (KOH). Data collection started on July 26, 2021, and included data from February 15, 2010, to May 16, 2020.

Results: Diabetes mellitus was the chief underlying condition related to mucormycosis. Rhino-cerebral, rhino-sino, and rhino-sino-orbital infections were observed in 53.2%, 23.8%, and 23% of these patients. Among the 108 cases with a culture, Rhizopus species were the most prevalent, followed by Mucor species. Over half of the patients received surgery/antifungal treatment, with an overall antifungal prescribing rate of 66.7% of patients within the study period. However, surgery was associated with better clinical outcomes than surgery/antifungal treatment. The antifungals prescribed were mainly amphotericin B, posaconazole, and amphotericin-posaconazole. Most patients with mucormycosis infection were admitted in the summer. Overall mortality in the identified cases was 30.6%, with the highest mortality rate in patients diagnosed with pulmonary infection.

Conclusion: The current study is the largest single-country retrospective study on the topic, with 601 mucormycosis cases. It may uncover gaps in knowledge, develop recommendations for future studies, and clarify the clinical and epidemiological aspects of mucormycosis. However, future studies and clarification of mucormycosis's clinical and epidemiological aspects are highly recommended.

Introduction: Aspergillus fumigatus poses significant clinical challenges due to its increasing azole resistance. This study investigates the sdh1 gene's role in regulating azole susceptibility, mitochondrial function, and virulence.

Materials and methods: Fungal strains were co-cultured with varying concentrations of succinate dehydrogenase inhibitors (SDHIs). Post-treatment azole minimum inhibitory concentrations (MICs) were determined using broth microdilution method, while succinate dehydrogenase subunit (SDH) expression changes were analyzed via RT-qPCR. Using A. fumigatus MFIG001 as the parental strain, sdh1 knockout mutant (Δsdh1) and complemented strain (Δsdh1::sdh1⁺) were constructed through homologous recombination. Detect the hyphal growth rate of Δsdh1, MICs and the changes in virulence within the Galleria mellonella infection model. Mitochondrial function was evaluated by measuring SDH activity, ATP content, and reactive oxygen species (ROS) levels. Transcriptomic changes were analyzed using RNA-seq and RT-qPCR, with efflux pump activity validated through Rhodamine 6G accumulation assays.

Results: Exposure to subinhibitory concentrations of SDHIs induced azole resistance in A. fumigatus, with 4.12% of strains exhibiting reduced susceptibility to voriconazole, itraconazole, and posaconazole. RT-qPCR analysis revealed significant downregulation of sdh1 in resistant strains, implicating its role in resistance development. Deletion of sdh1 resulted in an 8- to 16-fold increase in triazole MICs, confirming its role as a negative regulator of azole susceptibility. Phenotypically, the Δsdh1 strain exhibited impaired growth, reduced sporulation, and diminished efficacy of azole treatment in the G. mellonella infection model. Furthermore, Δsdh1 exhibited severe mitochondrial dysfunction, including reduced SDH activity, decreased ATP levels, elevated ROS, and impaired antioxidant defenses. RNA-seq analysis revealed that the deletion of sdh1 upregulated the expression of efflux pump genes (e.g., cdr1B, abcB, mdr4), while Rhodamine 6G efflux assays demonstrated significantly enhanced efflux activity.

Discussion: These results identify sdh1 as a critical determinant of azole susceptibility through dual mechanisms: mitochondrial function maintenance and efflux pump regulation. The observed SDHI-induced cross-resistance suggests agricultural fungicides may drive environmental selection of azole-resistant strains. While sdh1 deletion increased drug tolerance through efflux activation, the concurrent mitochondrial damage reduced pathogenic fitness, revealing compensatory evolutionary constraints. This work highlights the need to monitor non-target effects of agricultural SDHIs on clinical antifungal resistance.

Candida is a common and harmless component of the vaginal microbiota, present in approximately 50% of women of reproductive age. In specific conditions like pregnancy, Candida may cause chronic or recurrent infections which significantly impair quality of life. Additionally, due to the possibility of vertical transmission, it may lead to life-threatening infections in newborns. Timely screening, suspicion and identification of the causative agent are critical determinants of patient outcomes. Candida albicans (CA) remains the most prevalent species, but other non-albicans Candida (NAC) species and other non-Candida yeast (NCY) also play an important role in vulvovaginal infections. Due to the lack of precise local epidemiological data, this study aimed to determine the 10-year prevalence of CA, NAC and NCY species (spp.) in symptomatic pregnant women in Serbia using identification Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) for species identification. The total of 2,142 cases were examined (2013-2023) and the laboratory positivity was 48.3% (n = 1,035). The prevalence of CA, NAC and NCY were 74%, 23% and 3%, respectively. Biochemical and proteomic identification methods showed 100% concordance for CA, C. krusei (Pichia kudriavzevii), C. kefyr (Kluyveromyces marxianus), C. lusitaniae (Clavispora lusitaniae), and C. zeylanoides (Pichia norvengensis). Biochemical misidentification was observed for C. tropicalis (Lodderomyces sp.), C. glabrata (Nakaseomyces glabrata), and Saccharomyces cerevisiae. A global trend highlights the importance of renamed and reclassified yeast species in vaginal infections, supporting the reconsideration of the current disease name VVC in favor of the term vulvovaginal yeast infection (VYI). The prevalence of emerging NAC and NCY species is increasing but remains underestimated. There is a need for new laboratory diagnostic guidelines to enable timely and accurate identification, as this is crucial for guiding appropriate treatment and improving outcomes.

This report describes two cases of Curvularia geniculata keratitis, a rare form of fungal keratitis successfully managed with natamycin-based therapy. Both patients presented with characteristic feathery corneal infiltrates following ocular trauma. In vivo confocal microscopy and direct microscopy revealed septate filamentous fungi, and the isolates were definitively identified as C. geniculata through sequence analysis of the translation elongation factor 1-alpha (tef1-α) gene. Antifungal susceptibility testing showed sensitivity to natamycin at 2 μg/mL for both isolates, with variable sensitivity to other antifungal agents. Patient 1 was treated with a combination of topical natamycin and voriconazole, while Patient 2 received natamycin monotherapy. Both patients achieved complete healing and excellent visual outcomes. These cases underscore the importance of accurate molecular identification for species differentiation within the Curvularia genus and demonstrate the efficacy of natamycin-based therapy for C. geniculata keratitis. The choice between monotherapy and combination therapy may be guided by clinical severity and antifungal susceptibility testing. This report contributes to the understanding of the clinical features, diagnosis, and management of this rare condition and highlights the potential value of susceptibility testing in guiding treatment decisions.

Introduction: Fungal keratitis (FK), a severe ocular infection caused primarily by Fusarium spp. and Aspergillus spp., remains a major cause of blindness worldwide. Current treatment relies on antifungal agents, though emerging azole resistance in Aspergillus fumigatus complicates therapeutic outcomes.

Materials and methods: We isolated a clinical FK strain and assessed its antifungal susceptibility using broth microdilution and E-test methods, followed by sequencing of the cyp51A gene's promoter region and coding sequence (CDS) to identify resistance-associated mutations.

Results: The isolate, confirmed as A. fumigatus (Aftr46-001) via ITS and β-tubulin sequencing, exhibited elevated minimum inhibitory concentrations (MICs) 16 µg/mL for itraconazole (ITC), 32 µg/mL for isavuconazole (ISA), 32 µg/mL for voriconazole (VRC), and 1 µg/mL for posaconazole (POS) by broth microdilution. E-test results revealed an ITR MIC of 12 µg/mL, ISA MIC 32 µg/mL, VRC MIC 32 µg/mL, and POS MIC of 2 µg/mL. The isolate exhibited MICs values at or above the CLSI and EUCAST epidemiological cutoff values (ECVs): 1 µg/mL for ITC, ISA, and VRC according to CLSI (with insufficient data to establish a POS ECV), and 1 µg/mL for ITC and VRC, 2 µg/mL for ISA, and 0.25 µg/mL POS per EUCAST criteria. Genotypic analysis identified a 46-nucleotide tandem repeat in the cyp51A promoter and two nonsynonymous mutations (Y46F, F70L).

Discussion: This represents the first report of a cyp51A TR46/Y46F/F70L-harboring A. fumigatus strain isolated from FK, with potential agricultural environmental origins, suggesting that this mutation may have become a potential driver of azole-resistant FK in areas with high agricultural exposure, urgently needing to be included in local treatment guidelines and active surveillance systems. The isolate's resistance to all tested azoles underscores the clinical challenge posed by this genotype. Following this combined intervention, the patient's left eye vision improved from counting fingers at 1 m upon admission to a final visual acuity of 0.3, indicating that combined surgery and local high-dose drug delivery can serve as an effective strategy for drug-resistant FK. These findings highlight the importance of monitoring azole-resistant A. fumigatus strains to guide clinical treatment. The global increase in azole drug resistance further highlights the urgency and importance of rapid and accurate pathogen identification and drug resistance testing in the current environment.