Mycopathologia最新文献

Introduction: Invasive candidiasis is a serious healthcare associated infection with a high mortality rate. Emergence of the multi-drug-resistant species Candida (Candidozyma) auris over the past two decades poses further challenges. We aimed to study the epidemiology, clinical profile and outcomes of non-neutropenic adults with C. auris candidemia in comparison with candidemia due to other species.

Methods: We conducted a retrospective study of all non-neutropenic adult patients admitted to our tertiary care centre with blood culture proven candidemia between January 2019 and September 2024. We retrospectively collected their clinical data and investigation records via hospital's electronic records and document management systems.

Results: Out of a total of 372 candidemia episodes, 85 (22.8%) were caused by C. auris, which was the second most common species after C.tropicalis. The incidence of candidemia overall as well as C. auris candidemia increased during the SARS-COV2 pandemic. In comparison to other species, C. auris candidemia was associated with prolonged hospital stay, prior antifungal exposure, a lower SOFA score and was common in patients on ECMO. Candida endocarditis was associated with persistent candidemia and long, tunnelled lines. C. auris showed 100% resistance to fluconazole and very low rate of susceptibility to amphotericin B: only echinocandins were reliably effective. A negative beta-D glucan (BDG) value was seen in a quarter of patients with both C. auris as well as with other species. Overall survival at 28 days was only 40%. Advanced age and a high SOFA score were associated with higher mortality. C. auris was associated with a lower mortality overall but was not associated with higher mortality in a multi-variate analysis.

Conclusion: Multi-drug-resistant Candida (Candidozyma) auris has emerged as a major nosocomial pathogen in Indian ICUs since the SARS-COV-2 pandemic, especially later in the course of hospital stay and with prior antifungal exposure. A negative BDG result alone cannot be used for withholding or discontinuing antifungals. Echinocandins are the empiric antifungals of choice for candidemia in view of the current epidemiology and resistance profile.

Objectives: Invasive candidiasis, including candidaemia, is associated with high morbidity and mortality. Diagnosis is traditionally based on blood culture, which lacks sensitivity. Therefore, additional tools such as PCR-based diagnostic methods are increasingly used. The T2MR technology is based on polymerase chain reaction and detection of the PCR product involving magnetic resonance technology. In this study, we compare the T2Candida in a clinical routine setting to conventional blood culture in order to explore its usefulness, strengths and weaknesses in its daily application.

Methods: This retrospective analysis was performed at the Vienna University Hospital with clinical routine samples submitted between April 2021 and May 2024. Sensitivity, specificity, positive predictive value, negative predictive value and accordance were calculated with blood culture as reference method. Patients with a positive T2Candida result but a negative result in blood culture were assessed according to a clinical case definition. Based on direct detection in blood by alternative methods (e.g. blood culture, alternative PCR), 1-3-beta-D-Glucan, patient risk factors and detection of the same species in other sample materials, each result was categorised as "proven", "probable", "possible", "improbable" or "not assessable".

Results: 2105 samples from 1447 unique patients were submitted for analysis during the study period. 94 samples were positive (4.5%) in the T2Candida, with 4 samples positive for more than one target. 26 out of these 94 (27.7%) were also positive in blood culture. 339 (16.1%) samples were invalid. The most frequent species detected was Candida albicans/tropicalis with 57 detections. Overall sensitivity of the T2Candida panel in our setting was 0.62 (95% CI 0.41-0.80) and specificity was 0.96 (95% CI 0.95-0.97). Cases detected by the T2Candida panel were assessed as proven (n = 28), probable (n = 11), possible (n = 29), improbable (n = 15) and not assessable (n = 15). Median time-to-result was 3.9 h for the T2Candida compared to a median time-to-positivity of blood culture ranging from 22.7 to 42.0 h depending on the species.

Conclusions: The introduction of the T2Candida panel led to a substantial rise in patients diagnosed with invasive candidiasis. Combination of both the T2Candida panel and conventional blood culture led to the detection of more positive samples than each test alone.

Systemic candidiasis caused by Candida albicans has become a serious issue due to high morbidity and mortality. It is very important to develop novel and effective antifungal agents due to the increasing resistance to commonly used drugs such as fluconazole (FLC). In our previous research, the essential oil of Carica papaya L. seed (PSEO) was extracted and in vitro studies demonstrated that PSEO exhibited strong antifungal activity against C. albicans. It is crucial to investigate the therapeutic effect of PSEO in vivo to develop it into a viable antifungal agent. This study aimed to investigate acute toxicity of PSEO and its in vivo effects on a systemic candidiasis model in mice induced with both FLC-sensitive and -resistant C. albicans. The results showed that PSEO showed no acute toxicity up to 100 mg/kg. PSEO and FLC can improve the water intake, food intake, and mental state of systemic candidiasis model mice. The body weight of the infected mice recovered, the survival rate and splenic index increased, the fungal burden decreased, and pathological damage was alleviated to varying degrees. Moreover, the higher the dose of PSEO, the more pronounced the effect. PSEO exhibited significantly better efficacy than FLC against FLC-resistant C. albicans-induced systemic candidiasis. These findings indicate that PSEO holds great promise as a natural, novel, and effective agent for clinical treatment of C. albicans infections, especially for drug-resistant C. albicans infections. This study provides a theoretical basis for the rational development and utilization of papaya seeds.

Mannose-binding lectin (MBL) contributes to innate immunity against Aspergillus fumigatus. We assessed the role of reduced MBL levels in asthma patients with and without allergic bronchopulmonary aspergillosis (ABPA). In this prospective cross-sectional study, we enrolled 154 adults: 48 with asthma, 27 with Aspergillus-sensitized asthma (ASA, A. fumigatus-IgE ≥ 0.35 kUA/L), and 79 with ABPA. Serum MBL levels were quantified using enzyme-linked immunosorbent assay. Reduced MBL levels were defined using three thresholds (< 200, < 359, and < 500 ng/mL). The prevalence of reduced MBL levels did not differ significantly among the groups at any threshold. However, mean MBL levels were significantly lower in patients with ABPA (961 ng/mL) compared to asthma (1159 ng/mL) and ASA (1593 ng/mL; p = 0.048). Among ABPA patients, reduced MBL levels (≤ 359 ng/mL) were not associated with significant differences in clinical features, immunological markers, lung function, or radiology.

COVID-19-associated pulmonary aspergillosis (CAPA) significantly exacerbates the clinical outcomes of COVID-19 patients, contributing to heightened mortality. Aspergillus tracheobronchitis, a manifestation of invasive pulmonary aspergillosis, specifically involves the tracheobronchial tree. According to the 2020 European Confederation of Medical Mycology/International Society for Human and Animal Mycology (ECMM/ISHAM) consensus criteria, airway biopsy via bronchoscopy is the definitive method for CAPA diagnosis, underscoring its critical role in the management of COVID-19 patients. This case report describes an elderly male patient with COVID-19 who presented with extensive pseudomembranous involvement of the tracheobronchial tree, identified through bronchoscopy. The pseudomembrane, spanning from the glottis to the bronchi and characterized by its yellow-white translucency, was removed. Subsequent pathological examination and next-generation sequencing confirmed an Aspergillus infection. Despite the initiation of antifungal therapy, the patient's condition deteriorated, leading to his death.

Chronic hyperkeratotic tinea pedis is a treatment-resistant infection. We evaluated the efficacy of a 3-month course of topical 1% luliconazole in 21 hyperkeratotic tinea pedis patients. The diagnosis was confirmed through microscopy and culture. The lesion area was assessed monthly using a software program. Clinical responses were classified into five categories from "cured" to "no change." Among the isolates, one terbinafine-resistant T. rubrum strain was detected. The mean lesion area decreased significantly over 3 months, with an average improvement rate of 94.1% ± 12.7% and a cure rate of 61.9%. The mean amount of luliconazole used per foot was 27.5 ± 9.7 g monthly. The resistant case showed a partial improvement with topical luliconazole and was successfully treated with oral fosravuconazole. These findings suggest that 1% topical luliconazole is effective for treating hyperkeratotic tinea pedis.

Purpose: This study aims to investigate the clinical and molecular epidemiological characteristics of bloodstream infections caused by Candida tropicalis.

Methods: This retrospective study analyzed the clinical data of patients diagnosed with C. tropicalis bloodstream infections from January 2020 to December 2022. Antifungal susceptibility testing was performed. Multilocus sequence typing (MLST) was used to analyze strain homology, and mutation analysis of the ERG11 (azole resistance-associated) and FKS1 (echinocandin resistance-associated) genes was conducted.

Results: Among the 26 cases of C. tropicalis bloodstream infections, hematologic malignancies were the most common underlying condition, with an overall mortality rate of 38.5%. Resistance rates to voriconazole and fluconazole were 30.8%, while the isolates exhibited high susceptibility to echinocandin drugs and amphotericin B. All fluconazole-resistant strains contained mutations in the ERG11 gene, with Y132F and S154F being the most frequent mutation sites. The mortality rate in fluconazole-resistant patients (37.5%) was similar to that of susceptible or dose-dependently susceptible patients (38.8%). A total of 20 distinct sequence types (DSTs) were identified among the 26 strains, all of which were previously known, indicating significant genetic diversity. The most abundant type was DST376.

Conclusion: Hematologic malignancies are the most common underlying disease of C. tropicalis bloodstream infections. The isolated strains demonstrate significant genetic diversity and a high level resistance to fluconazole.

Cryptococcosis, a rare deep fungal infection, primarily affects immunocompromised individuals and carries a high mortality risk when hematogenously disseminated to the central nervous system (CNS). Cutaneous cryptococcosis poses diagnostic challenges due to its diverse and nonspecific dermatological manifestations. Traditional diagnostic methods, including mycological examination, culture, and histopathology, are time-consuming and require specialized expertise, often leading to misdiagnosis. Metagenomic next-generation sequencing (mNGS), an advanced molecular tool, enables rapid and unbiased pathogen identification. Here, we present the first documented case of cutaneous cryptococcosis diagnosed via mNGS, demonstrating its pivotal role in guiding timely treatment despite negative initial conventional tests.

Introduction: Since December 2019, a serious health crisis caused by severe acute respiratory syndrome-Coronavirus-2 affected all aspects of human lives. The available data about COVID-19-associated Rhino-Orbital-Cerebral Mucormycosis (CA-ROCM) survival issues are based on studies on small populations with limited follow-up durations. Therefore, this multicenter cohort of a large population with CA-ROCM is aiming to report the one-year survival rate and investigate the potential responsible risk factors affecting the mortality.

Materials and methods: This prospective, longitudinal, multicenter study included CA-ROCM patients from eight tertiary ophthalmology centers across Iran. Demographic, clinical, and therapeutic data were collected and patients were followed for a year. Survival analysis was performed using Cox proportional hazards models to identify mortality-associated risk factors. The research protocol is also available on ClinicalTrials.gov (NCT05097664).

Results: Among the 246 patients, 183 (74.4%) survived within a year and 63 (25.6%) died. Significant mortality risk factors included need for orbital exenteration (HR = 3.01 vs. other treatments, p = 0.019), advanced disease stage (HR = 2.43 stage IV vs. II, p = 0.02), age (HR = 1.05, p < 0.001), and diabetes duration (HR = 1.05, p = 0.002). Paradoxically, steroid administration for COVID management was associated with improved survival (HR = 2.72 for no steroids, p = 0.018).

Discussion: COVID-19-associated Rhino-Orbital-Cerebral Mucormycosis carries a substantial one-year survival rate of 74.4% in Iran. Age, diabetes, advanced disease stage, and need for orbital exenteration are the probable fatal risk factors. Interestingly, administration of steroids for COVID management was associated with a better survival.