Prevalence of fungal DNAemia mediated by putatively non-pathogenic fungi in immunocompromised patients with febrile neutropenia: a prospective cohort study

Authors	LUCINI Chantal OBROVA Klara KRICKL Isabella NOGUEIRA Filomena KOCMANOVA Iva HERNDLHOFER Susanne GLEIXNER Karoline V SPERR Wolfgang R FRANK Tijana ANDRADE Nuno PETERS Christina ENGSTLER Gernot DWORZAK Michael ATTARBASCHI Andishe VAN GROTEL Martine VAN DEN HEUVEL-EIBRINK Marry M MOISEEV Ivan S ROGACHEVA Yuliya ZUBAROVSKAYA Ludmilla ZUBAROVSKAYA Natalia PICHLER Herbert LAWITSCHKA Anita KOLLER Elisabeth KEIL Felix MAYER Jiří WEINBERGEROVÁ Barbora VALENT Peter LION Thomas
Year of publication	2024
Type	Article in Periodical
Magazine / Source	JOURNAL OF HEMATOLOGY & ONCOLOGY
MU Faculty or unit	Faculty of Medicine
Citation
Web	https://jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01583-0
Doi	http://dx.doi.org/10.1186/s13045-024-01583-0
Keywords	Invasive fungal disease; panfungal-PCR; Fungal diagnostic; Antifungal therapy; Antifungal treatment
Description	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.