Invasive fungal disease (IFD) presents a life-threatening condition in immunocompromised patients, thus often prompting empirical administration of antifungal treatment, without adequate mycological evidence. Over the past years, wide use of antifungal prophylaxis resulted in decreased occurrence of IFD but has contributed to changes in the spectrum of fungal pathogens, revealing the occurrence of previously rare fungal genera causing breakthrough infections. The expanding spectrum of clinically relevant fungal pathogens required the implementation of screening approaches permitting broad rather than targeted fungus detection to support timely onset of pre-emptive antifungal treatment. To address this diagnostically important aspect in a prospective setting, we analyzed 935 serial peripheral blood (PB) samples from 195 pediatric and adult patients at high risk for IFD, involving individuals displaying febrile neutropenia during treatment of hematological malignancies or following allogeneic hematopoietic stem cell transplantation. Two different panfungal-PCR-screening methods combined with ensuing fungal genus identification by Sanger sequencing were employed. In the great majority of PB-specimens displaying fungal DNAemia, the findings were transient and revealed fungi commonly regarded as non-pathogenic or rarely pathogenic even in the highly immunocompromised patient setting. Hence, to adequately exploit the diagnostic potential of panfungal-PCR approaches for detecting IFD, particularly if caused by hitherto rarely observed fungal pathogens, it is necessary to confirm the findings by repeated testing and to identify the fungal genus present by ensuing analysis. If applied appropriately, panfungal-PCR-screening can help prevent unnecessary empirical therapy, and conversely, contribute to timely employment of effective pre-emptive antifungal treatment strategies.

3rd Medical Dept Hanusch Hospital Vienna Austria

Department of Clinical Microbiology and Immunology University Hospital Brno Brno Czech Republic

Department of Internal Medicine 1 Division of Hematology and Hemostaseology Medical University of Vienna Vienna Austria

Department of Internal Medicine Haematology and Oncology Masaryk University Brno Czech Republic

Department of Internal Medicine Haematology and Oncology University Hospital Brno Brno Czech Republic

Department of Paediatrics Medical University of Vienna Vienna Austria

Department of Pediatrics St Anna Children's Hospital Medical University of Vienna Vienna Austria

Division of Childhealth Wilhelmina Childrens Hospital University of Utrecht Utrecht the Netherlands

Ludwig Boltzmann Institute for Hematology and Oncology Medical University of Vienna Vienna Austria

Princess Máxima Centre for Paediatric Oncology Utrecht the Netherlands

RM Gorbacheva Children Research Institute Pavlov University Saint Petersburg Russian Federation

St Anna Children's Cancer Research Institute Zimmermannplatz 10 Vienna A 1090 Austria

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NCT02492594