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宏基因组下一代测序在异基因造血干细胞移植患者口咽定植筛查中的临床价值:一项前瞻性观察研究。

Clinical value of metagenomic next-generation sequencing in screening oropharyngeal colonization in patients undergoing allogeneic hematopoietic stem cell transplantation: a prospective observational study.

作者信息

Zhang Yuqi, Ge Jianrong, Wang Yuhang, Tang Zaixiang, Ma Xiao, Liu JIsheng, Wu Depei, Wu Xiaojin

机构信息

First Affiliated Hospital of Soochow University, Suzhou, China.

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Suzhou, Jiangsu, China.

出版信息

Microbiol Spectr. 2025 Jul;13(7):e0002825. doi: 10.1128/spectrum.00028-25. Epub 2025 May 27.

DOI:10.1128/spectrum.00028-25
PMID:40422860
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12210989/
Abstract

UNLABELLED

Screening for colonization is an essential procedure in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although metagenomic next-generation sequencing (mNGS) has played an important role in the diagnosis of complex and challenging infections, its effectiveness in screening oropharyngeal colonization is not yet fully assessed. We performed a prospective analysis (ChiCTR2300069450) involving 128 allo-HSCT patients between June 2022 and June 2023. Before the conditioning regimen, all patients underwent oropharyngeal and anal swab tests to detect colonizing pathogens. In addition to culture-based methods, we also analyzed oropharyngeal swab samples using mNGS. Among the allo-HSCT patients, the overall colonization rate from cultures was 15.6%, while mNGS identified an oropharyngeal colonization rate of 49.2%. Patients with oropharyngeal Enterobacteriaceae colonization had a higher incidence of post-transplant bloodstream infection (BSI) (39.1% vs 19.0%, = 0.034) and thrombotic microangiopathy (17.4% vs 8.5%, = 0.04). Multivariate analysis confirmed oropharyngeal Enterobacteriaceae colonization as an independent risk factor for non-relapse mortality (NRM), overall survival (OS), and progression-free survival (PFS) ( = 0.024, 0.030, and 0.021, respectively). The individuals with carbapenem-resistant Enterobacteriaceae (CRE) colonization experienced delayed platelet engraftment ( = 0.018). Moreover, they had significantly worse OS ( = 0.002), higher NRM ( = 0.00015), and poorer PFS ( = 0.00095). Screening for oropharyngeal colonization using mNGS provides critical clinical value in predicting transplant prognosis. Clinicians should closely monitor patients with oropharyngeal Enterobacteriaceae or CRE colonization.

IMPORTANCE

Screening for colonization is essential for predicting infection risk in allo-HSCT patients. Traditional microbiological testing methods, however, are time-consuming and have low sensitivity. In this paper, we examine the impact of oropharyngeal colonization on outcomes following allo-HSCT while also evaluating the utility of mNGS for detecting colonization. Our investigation reveals that screening for oropharyngeal colonization using mNGS provides critical clinical value in predicting transplant outcomes and prognosis. Additionally, not all colonization has clinical relevance, but oropharyngeal Enterobacteriaceae colonization has negative impacts on transplant prognosis. Colonization by CRE had particularly severe consequences, which warrants serious attention.

CLINICAL TRIALS

This study is registered as a single-center clinical trial (Registration No. ChiCTR2300069450).

摘要

未标注

在异基因造血干细胞移植(allo-HSCT)中,筛查定植是一项必不可少的程序。尽管宏基因组下一代测序(mNGS)在复杂且具有挑战性的感染诊断中发挥了重要作用,但其在筛查口咽定植方面的有效性尚未得到充分评估。我们进行了一项前瞻性分析(ChiCTR2300069450),纳入了2022年6月至2023年6月期间的128例allo-HSCT患者。在预处理方案前,所有患者均接受口咽和肛门拭子检测以检测定植病原体。除了基于培养的方法外,我们还使用mNGS分析口咽拭子样本。在allo-HSCT患者中,培养法检测到的总体定植率为15.6%,而mNGS检测到的口咽定植率为49.2%。口咽肠杆菌科定植的患者移植后血流感染(BSI)的发生率更高(39.1%对19.0%,P = 0.034),血栓性微血管病的发生率也更高(17.4%对8.5%,P = 0.04)。多因素分析证实口咽肠杆菌科定植是影响非复发死亡率(NRM)、总生存期(OS)和无进展生存期(PFS)的独立危险因素(分别为P = 0.024、0.030和0.021)。耐碳青霉烯类肠杆菌科(CRE)定植的个体血小板植入延迟(P = 0.018)。此外,他们的OS明显更差(P = 0.002),NRM更高(P = 0.00015),PFS更差(P = 0.00095)。使用mNGS筛查口咽定植对预测移植预后具有重要临床价值。临床医生应密切监测口咽肠杆菌科或CRE定植的患者。

重要性

筛查定植对于预测allo-HSCT患者的感染风险至关重要。然而,传统的微生物检测方法耗时且灵敏度低。在本文中,我们研究了口咽定植对allo-HSCT后结局的影响,同时评估了mNGS检测定植的效用。我们的研究表明,使用mNGS筛查口咽定植对预测移植结局和预后具有重要临床价值。此外,并非所有定植都具有临床相关性,但口咽肠杆菌科定植对移植预后有负面影响。CRE定植的后果尤为严重,值得高度关注。

临床试验

本研究注册为单中心临床试验(注册号:ChiCTR2300069450)。

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