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.

中文翻译：

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免疫功能低下发热性中性粒细胞减少症患者由推定的非致病性真菌介导的真菌 DNA 血症患病率：一项前瞻性队列研究


侵袭性真菌病 （invasive fungal disease， IFD） 在免疫功能低下患者中表现为危及生命的疾病，因此在没有足够真菌学证据的情况下，通常会促使经验性给予抗真菌治疗。在过去几年中，抗真菌预防的广泛使用导致 IFD 的发生率降低，但有助于真菌病原体谱的变化，揭示了以前罕见的真菌属的发生导致突破性感染。不断扩大的临床相关真菌病原体需要实施筛查方法，允许广泛而不是靶向真菌检测，以支持及时开始先发制人的抗真菌治疗。为了在前瞻性环境中解决这一诊断上重要的方面，我们分析了来自 195 名 IFD 高危儿童和成人患者的 935 份系列外周血 （PB） 样本，涉及在血液系统恶性肿瘤治疗期间或同种异体造血干细胞移植后表现出发热性中性粒细胞减少症的个体。采用两种不同的泛真菌 PCR 筛选方法，随后通过 Sanger 测序进行真菌属鉴定。在绝大多数显示真菌性 DNA 血症的 PB 标本中，研究结果是短暂的，即使在免疫功能高度低下的患者环境中，也揭示了通常被认为是非致病性或很少致病性的真菌。因此，为了充分利用泛真菌 PCR 方法检测 IFD 的诊断潜力，特别是由迄今为止很少观察到的真菌病原体引起，有必要通过重复测试来确认结果，并通过随后的分析来识别存在的真菌属。 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性抗真菌治疗策略。