Systemic Mycosis
Conditions
Brief summary
Invasive fungal infections (IFI) in immunocompromised patients pose a major challenge for diagnostics designed to permit timely onset of appropriate treatment. The aim of the current clinical-diagnostic studies, one in in pediatric and one in adult patients at high risk of IFI, is to test newly developed diagnostic approaches to invasive fungal infections in relation to established procedures. The studies will be performed in a prospective, blinded fashion, and represent a work package within the FUNGITECT grant supported by the European Commission. The studies will focus on analyses of blood-samples from patients with febrile neutropenia during treatment of acute leukaemia and other tumour entities, and patients undergoing allogeneic stem cell transplantation treated with intensive chemotherapy.
Detailed description
Samples from immunosuppressed patients with febrile neutropenia (NP - defined as fever ≥ 38.5ºC and \<500 ANC) will be taken: * at the start of neutropenic fever * after 24 hours * after 48 hours * before the start of antimycotic therapy, if pertinent * at the end of antimycotic therapy, if pertinent The results ot analyses by a panfungal PCR screening assay developed at our institution (European patent No 1960536) and methods newly developed during the FUNGITECT project will be compared with conventional methods for fungal diagnostics such as HR (High Resolution)-CT, serological testing, histology and fungal culture. Additionally, genomic approaches will be employed to investigate host- and pathogen-related factors of susceptibility, pathogenicity and antimycotic resistance.
Interventions
Peripheral blood samples will be taken at 3-5 defined timepoints during febrile neutropenia: * at the start of neutropenic fever * after 24 hours * after 48 hours * before the start of antimycotic therapy, if pertinent * at the end of antimycotic therapy, if pertinent
Sponsors
St. Anna Kinderkrebsforschung
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Months to 90 Years
Healthy volunteers
No
Inclusion criteria
Adult study: * Patients between 18-90 years of age with high risk of invasive fungal infections * signed informed consent Pediatric study: * patients between 0-18 years of age with high risk of invasive fungal infections * signed informed consent
Exclusion criteria
Adult study: * pregnancy * no consent Pediatric study: \- no consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of fungal pathogens resistant to commonly used antifungal agents | until the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia) | Progress and changes in healthcare practices provide opportunities for new and drug-resistant fungal pathogens emerging in hospital settings. |
| Frequency of individual fungal pathogens during febrile neutropenia in high risk patients | until the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia) | The frequency of invasive fungal disease in the paediatric and adult patient cohorts as well as in each individual patient will be elucidated. |
| Number of patients with fungal DNAmia (as indicator of fungal infection) detected by new methodologies described in the proposal | until the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia) | Invasive fungal diseases will be evaluated by developing improved diagnosis: technical validation of individual assays (PCR-based, NGS, and protein-based), validation of biomarkers in clinical specimens (MoAbs, proteinaceous infection markers) and optimized for time and parallel processing of samples by establishing a robust protocol to generate reproducible results, implementation of automated or semi-automated techniques and by use of defined quality control systems. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of lethal fungal infections | until the end of antifungal treatment (up to 6 weeks after the onset of febrile neutropenia) | Evaluation of potentially life-threatening fungal infections according to EORTC criteria. |
Countries
Austria, Netherlands, Russia
Outcome results
None listed