Mycoses最新文献

Introduction: Relapses occur in up to 40% of patients after prolonged courses of antifungal treatment for chronic pulmonary aspergillosis (CPA). The factors predisposing to relapse remain poorly defined.

Methods: We conducted a retrospective study of adults treated for ≥ 6 months with oral azoles for CPA. Patients who completed antifungal therapy and were deemed not to require further treatment were included. Demographic, clinical, radiological and serological data at treatment completion were collected. CPA relapse was defined as symptomatic and radiological deterioration leading to re-initiation of antifungal therapy. Cox regression and Kaplan-Meier analyses were used to identify predictors of relapse and mortality.

Results: Among 125 patients (56% male; mean age 61 years), median treatment duration was 36 months. Thirty-two (26%) developed relapse; relapse rate at 1 year was 16%. Aspergillus sensitisation (specific IgE > 0.35 IU/mL) and elevated Aspergillus-specific IgG (> 40 mg/L) at treatment completion were independently associated with relapse (p < 0.05). No patient with IgG < 40 mg/L relapsed. Underlying lung disease (COPD or prior tuberculosis), extent of radiological involvement, or treatment duration were not significantly associated with relapse or mortality.

Conclusions: Aspergillus sensitisation and persistently elevated Aspergillus-specific IgG at the end of antifungal therapy were independent predictors of CPA relapse. These parameters may reflect ongoing fungal airway burden and can help identify patients requiring extended or closer post-treatment follow-up. Underlying comorbidities were not associated with relapse risk.

Background: Candida (Candidozyma) auris is an emerging yeast that poses a significant global health threat due to its multidrug resistance and ability to cause healthcare-associated outbreaks. Genomic surveillance is essential for monitoring spread, transmission and antifungal resistance.

Objectives: To report the first identification and genomic characterisation of C. auris in the state of Minas Gerais, Southeast Brazil, and to investigate the genetic origin and diversity, resistance-associated mutations, and potential transmission dynamics during a hospital outbreak.

Methods: Eight C. auris isolates were collected during a hospital outbreak in Belo Horizonte, Minas Gerais, Brazil, including clinical samples from patients and environmental samples from surfaces in the Intensive Care Unit (ICU). Epidemiological investigation, whole-genome sequencing (WGS) and phylogenomic analyses were conducted to determine circulating clade, genetic diversity, outbreak origin and the presence of antifungal resistance mutations.

Results: All isolates were classified as clade IV and exhibited high genomic similarity to strains previously reported in northern Colombia (Caribbean coast). One isolate carried the ERG11 Y132F mutation, associated with fluconazole resistance, but this mutation was absent in another isolate from the same patient collected 1 day earlier, indicating mixed fungal populations. Environmental isolates clustered tightly with clinical strains, supporting surface-mediated transmission in the ICU.

Conclusions: This study describes the introduction and local spread of clade IV C. auris in Minas Gerais, Brazil. The findings underscore the critical role of genomic surveillance in identifying resistance mechanisms, tracing transmission pathways and guiding public health responses.

The Mycoses Study Group Education and Research Consortium (MSGERC)-a group comprising clinicians, researchers, patients, and industry partners-meets every 2 years to review the most significant challenges facing the clinical mycology community and plan research, education, and advocacy strategies to prevent fungal infections and improve outcomes. Key themes of the 2024 biennial meeting included emergence of antifungal resistance, the effects of climate change on incidence of IFI, recent healthcare-and community-associated outbreaks and their management, and the potential benefits of novel approaches, such as innovative study designs, host-directed diagnostics and therapies, and artificial intelligence in clinical and academic mycology.

Background: Invasive fungal infections (IFI) are a prominent cause of morbidity and mortality among patients with haematological malignancies (HMs). Diagnostic work-up excluding IFI is mandatory in case of persistent fever while antifungal treatment (AFT) is started.

Objectives: We aimed to describe antifungal prophylaxis (AFP) and AFT among haematological patients with IFI managed in clinical practice, focusing on microbiological and radiological characteristics, 30-day outcome and therapeutic options after AFT failure.

Patients and methods: We enrolled 461 consecutive adult and paediatric patients with HMs, in which an intravenous AFT was started from September 2019 to December 2021. After serum galactomannan (GM) and chest CT scan, they were stratified as presenting with proven, probable, and possible IFI according to 2008 EORTC-MSG criteria. Fungal isolates were detected from culture tests in 17.5% and from biopsy in 1.5% of patients. Mould active and non-active AFP was used in 42.3% and 16.5% of cases, respectively.

Results: Use of AFP significantly impact on serum GM negativity (p < 0.001 for mould active and p = 0.04 for mould non active, respectively). Use of mould non-active prophylaxis significantly correlates with radiological imaging (typical p = 0.0037, IC (0.370-0.825) and negative -p = 0.0031, IC (0.241-0.750)). Toxicity, progression, and drug interaction were responsible for therapy change in 58 (12%) patients: 18 patients with proven/probable IFI needed multiple courses of AFT. At 30 days from starting AFT, overall mortality with IFI was 23/461 (5%).

Conclusions: In this observational study, we recorded an impact of AFP on serum GM results and radiological imaging. Need of AFT should be carefully evaluated, as diagnostic work-up might be affected not only by specific disease risk but also by previous AFP.

Background: Since rifabutin has less severe drug interactions, it is preferred over rifampin when administered concomitantly with azole antifungals. However, limited data exist to evaluate this interaction.

Methods: This was a single-centre study of hospitalised patients who received concomitant isavuconazole and rifabutin prior to plasma isavuconazole therapeutic drug monitoring. Isavuconazole was administered at a standard dose of isavuconazonium sulphate 372 mg every 8 h for six doses followed by 372 mg every 24 h.

Results: Of the seven patients included, the median age (range) was 53 years (33-67), 71% (5/7) were solid organ transplant recipients and no patients had underlying cirrhosis. The median (range) corrected 24-h steady-state isavuconazole was 2.7 mg/L (0.7-3.7) and 86% (6/7) had an isavuconazole level > 1 mg/L. The median (range) area under the curve (AUC 24), half-life (T_½) and clearance (Cl) were 85 mg/L h (33-112), 13.1 h (6.8-17.8) and 4 L/h (3.1-10.7), respectively.

Conclusion: This study demonstrates that isavuconazole trough concentrations are often maintained above 1 mg/L despite patients being on concomitant rifabutin. However, therapeutic drug monitoring is mandatory in this setting. Further research is warranted to confirm these results.

Background: Typing Aspergillus species is crucial for understanding the sources of infection in hospital environments.

Objectives: This study analysed clinical and air samples as well as their relationship with the clinical forms of aspergillosis. Additionally, we examined the usefulness of the Short Tandem Repeats (STR) technique with two highly discriminatory markers for analysing the Aspergillus fumigatus (A. fumigatus) profile.

Patients/methods: Seventy-five air samples (September 2013-July 2014) and 116 clinical samples (2009-2014) were collected in a university hospital. Seventy-two samples were typed by STR with two markers, MC3 and MC5.

Results: Of the 75 air samples collected, 10 were positive in the Bone Marrow Transplant unit, a ventilated unit with HEPA filters as were 18 in the Haematology ward, a naturally ventilated unit. Of the 116 clinical samples of Aspergillus spp., 95 were identified as A. fumigatus. High diversity was found, with 42 genotypes in 67 clinical samples and four in five environmental samples. Most isolates were collected during the demolition and renovation of the Emergency unit in the Hospital from 2013 to 2014. Genotype 1 was found in several units during different years. Despite the heterogeneity, identical genotypes were observed three times at short intervals in the same or different wards. Some of these identical genotypes were confirmed as possible clones by genome sequencing while others' genotyping matches failed to be confirmed.

Conclusion: Despite the diversity of clinical and environmental samples, useful correlations can be established in invasive aspergillosis surveillance programs by using this simple STR method as a preliminary step.

Fungal infections are increasingly recognised as a global health challenge, responsible for millions of cases annually and substantial mortality, especially in immunocompromised individuals. Yet, the diagnosis of these infections remains notoriously difficult, often delayed by slow culture-based methods or hindered by the high cost and infrastructure demands of molecular diagnostics. In recent years, infrared (IR) spectroscopy has emerged as a promising alternative, offering rapid, cost-effective and reagent-free identification of human pathogenic fungi. This review provides an in-depth examination of how IR-based techniques, specifically, mid-infrared (MIR) and near-infrared (NIR) spectroscopy, are being applied in medical mycology. We explore the underlying chemical principles and highlight how recent advances in multivariate analysis and machine learning have enhanced their diagnostic accuracy. Studies have demonstrated the capacity of IR spectroscopy to accurately identify and type major fungal pathogens, while also providing insights into antifungal resistance profiles and outbreak tracking. While challenges remain, particularly regarding protocol standardisation and expansion of spectral databases, IR spectroscopy stands out as a valuable diagnostic strategy, especially in resource-limited settings. By reducing diagnostic time and cost, and expanding accessibility, IR-based methods have the potential to transform the clinical management of fungal infections, contributing to faster decision-making and improved patient outcomes.

Background: Recent literature indicates a decline in rates of candidemia in the general population.

Objectives: To analyse temporal trends in candidemia among patients with solid tumours and haematological malignancies admitted to a dedicated cancer centre.

Methods: We retrospectively reviewed all episodes of candidemia from July 2008 to June 2020 (12-year period). The incidence of candidemia was estimated as the number of new cases per 1000 patient days of hospital admission quarterly. A linear regression model was used to analyse changes in incidence rates.

Results: Over a 12-year period a total of 212 episodes of candidemia were identified with 90 (42.5%) occurring in patients with haematological malignancies and 122 (57.5%) in patients with solid tumours. The overall incidence of candidemia was 0.49 episodes per 1000 patient-days of admission per quarter. There was a significant decline in the incidence of candidemia overtime for the overall cohort (from 0.81 to 0.21 patient days per quarter, p < 0.001). This decline was statistically significant in patients with solid tumours (from 0.91 to 0.18 patient days per quarter, p < 0.001) with only a downward trend noted in patients with haematological malignancies (from 0.65 to 0.25 patient days per quarter, p = 0.052).

Conclusions: We observed a global decline in episodes of candidemia in patients with malignancies mainly driven by a decrease in patients with solid tumours. Patients with haematological malignancies continue to experience considerable rates of candidemia.

Background: Data on the epidemiology, diagnostic methods and evidence-based recommended treatment methods for children with mucormycosis who have undergone Haematopoietic stem cell transplantation (HSCT) are limited.

Objective: Summarise past recommendations and the latest literature on the treatment of HSCT in children with mucorin infection and clarify the epidemiology, diagnosis, treatment and outcomes of this invasive fungal disease.

Methods: A comprehensive search for full-text studies involving humans that were published in English between January 2000 and December 2022 was conducted in Ovid MEDLINE and Ovid Embase using various key words and MeSH terms.

Results: A total of 951 articles were identified in the initial database search, of which 28 (32 individual patients) were included in the final analysis. The majority of HSCT recipients (14/26, 54%) had a diagnosis of mucormycosis within 30 days posttransplant, with a median time from transplant to diagnosis of 19 (27 patients; IQR, 13-213) days. Pulmonary mucormycosis (9/32, 28%) and disseminated mucormycosis (9/32, 28%) were the most commonly observed manifestations in paediatric patients after HSCT. Targeted antifungal therapy was used in 27 patients. Iv AmB formulations were the most commonly administered first-line treatment (26/27, 96%). Compared with iv AmB monotherapy, initial treatment with combination antifungal therapy appeared to improve all-cause mortality [3/10 (30%) vs. 6/17 (35%)].

Conclusions: The results of the present review will help to determine the pathology, diagnosis, treatment and outcomes of this invasive fungal disease.

Invasive candidiasis is a life-threatening infection associated with high morbidity, mortality and healthcare costs in both general and critical care settings. Timely diagnosis and adequate antifungal treatment are essential to improving patient outcomes and limiting unnecessary use of healthcare resources. This review explores the relationship between early Candida clearance with antifungal therapy, clinical outcomes, resistance patterns and economic impact. It also evaluates the role of diagnostic markers in facilitating early and accurate identification of candidaemia, enabling more precise and effective clinical management. Special attention is given to the challenges of managing candidaemia in critically ill and neutropenic patients, highlighting the need for tailored and timely interventions in these vulnerable populations.