Lucini Chantal, Obrová Klára, Krickl Isabella, Nogueira Filomena, Kocmanová 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
St. Anna Children's Cancer Research Institute (CCRI), Zimmermannplatz 10, Vienna, A-1090, Austria.
Department of Clinical Microbiology and Immunology, University Hospital Brno, Brno, Czech Republic.
J Hematol Oncol. 2024 Aug 7;17(1):63. doi: 10.1186/s13045-024-01583-0.
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.
侵袭性真菌病（IFD）在免疫功能低下的患者中是一种危及生命的疾病，因此常常在没有充分真菌学证据的情况下促使进行抗真菌治疗的经验性用药。在过去几年中，抗真菌预防措施的广泛使用导致IFD的发生率降低，但也导致了真菌病原体谱的变化，揭示了以前罕见的真菌属引发突破性感染的情况。临床相关真菌病原体谱的扩大要求实施筛查方法，以允许进行广泛而非针对性的真菌检测，以支持及时开始抢先抗真菌治疗。为了在前瞻性研究中解决这一重要的诊断问题，我们分析了195例儿科和成人IFD高危患者的935份连续外周血（PB）样本，这些患者包括在血液系统恶性肿瘤治疗期间或异基因造血干细胞移植后出现发热性中性粒细胞减少的个体。采用了两种不同的泛真菌PCR筛查方法，并通过桑格测序对随后鉴定的真菌属进行了鉴定。在绝大多数显示真菌血症的PB样本中，检测结果是短暂的，所发现的真菌通常被认为是非致病性的，甚至在免疫功能高度低下的患者中也是很少致病的。因此，为了充分利用泛真菌PCR方法检测IFD的诊断潜力，特别是在由迄今罕见的真菌病原体引起的情况下，有必要通过重复检测来确认结果，并通过后续分析来鉴定存在的真菌属。如果应用得当，泛真菌PCR筛查有助于防止不必要的经验性治疗，反之，有助于及时采用有效的抢先抗真菌治疗策略。
