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血浆微生物游离DNA测序在确定实体器官移植受者感染综合征微生物病因方面的临床应用。

Clinical utility of plasma microbial cell-free DNA sequencing in determining microbiologic etiology of infectious syndromes in solid organ transplant recipients.

作者信息

Shah Jesal R, Sohail Muhammad Rizwan, Lasco Todd, Goss John A, Mohajer Mayar Al, Khalil Sarwat

机构信息

Baylor College of Medicine, Department of Medicine, Section of Infectious Diseases, Houston, TX, USA.

Baylor College of Medicine, Department of Pathology and Immunology, Houston, TX, USA.

出版信息

Ther Adv Infect Dis. 2024 Dec 23;11:20499361241308643. doi: 10.1177/20499361241308643. eCollection 2024 Jan-Dec.

DOI:10.1177/20499361241308643
PMID:39717490
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11664510/
Abstract

BACKGROUND

Metagenomic next-generation sequencing (mNGS) is increasingly being used for microbial detection in various infectious syndromes. However, data regarding the use of mNGS in solid organ transplant recipients (SOTR) are lacking.

OBJECTIVES

To describe and analyze real-world clinical impact of mNGS using plasma microbial cell-free DNA (mcfDNA) in SOTR.Design: Retrospectively reviewed all adult SOTR who underwent mNGS testing using plasma mcfDNA at Baylor St Luke's Medical Center from March 2017 to February 2023.

METHODS

Clinical impact (positive, neutral, and negative) was assessed using standardized objective criteria. Three Infectious Diseases physicians independently performed clinical adjudication to determine the correlation of mcfDNA results with clinical diagnosis. A descriptive analysis of the patient and clinical characteristics was performed.

RESULTS

A total of 113 mcfDNA tests in liver (42%), kidney (35%), lung (20%) and heart (13%) transplant recipients were performed in the study period. The most common clinical syndromes were pneumonia (36%), fever of unknown origin (16%), and intra-abdominal infections (15%). Most (80, 71%) of the mcfDNA test results were positive for microorganisms. Twenty-seven (24%) cases were classified as positive clinical impact, 82 (73%) were neutral and 4 (3%) were negative, respectively.

CONCLUSION

In SOTR, mcfDNA sequencing can add a positive clinical impact in a quarter of the cases and identify microorganisms beyond conventional microbiological testing across clinical syndromes. The negative clinical impact was rare. However, larger prospective studies are needed to define the optimal timing and utilization of mcfDNA in the sequence of diagnostic evaluation for syndrome-specific workup in SOTR.

SUMMARY

Metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool that can identify difficult-to-detect microorganisms in SOTR. Our study demonstrates that the mNGS test resulted in a positive clinical impact in 1 out of 4 patients.

摘要

背景

宏基因组下一代测序(mNGS)越来越多地用于各种感染综合征的微生物检测。然而,关于mNGS在实体器官移植受者(SOTR)中的应用数据尚缺。

目的

描述和分析mNGS使用血浆微生物游离DNA(mcfDNA)在SOTR中的实际临床影响。

设计

回顾性分析2017年3月至2023年2月在贝勒圣卢克医疗中心接受血浆mcfDNA的mNGS检测的所有成年SOTR。

方法

使用标准化客观标准评估临床影响(阳性、中性和阴性)。三名传染病医生独立进行临床判定,以确定mcfDNA结果与临床诊断的相关性。对患者和临床特征进行描述性分析。

结果

在研究期间,对肝脏(42%)、肾脏(35%)、肺(20%)和心脏(13%)移植受者共进行了113次mcfDNA检测。最常见的临床综合征为肺炎(36%)、不明原因发热(16%)和腹腔内感染(15%)。大多数(80例,71%)mcfDNA检测结果微生物呈阳性。27例(24%)病例被分类为临床影响阳性,82例(73%)为中性,4例(3%)为阴性。

结论

在SOTR中,mcfDNA测序在四分之一的病例中可产生积极的临床影响,并能识别出传统微生物检测无法检测到的跨临床综合征的微生物。负面临床影响很少见。然而,需要更大规模的前瞻性研究来确定mcfDNA在SOTR综合征特异性检查诊断评估序列中的最佳时机和应用。

总结

宏基因组下一代测序(mNGS)是一种新型诊断工具,可识别SOTR中难以检测的微生物。我们的研究表明,mNGS检测对四分之一的患者产生了积极的临床影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd71/11664510/b02f4cfca9b6/10.1177_20499361241308643-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd71/11664510/9cdbf82669f4/10.1177_20499361241308643-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd71/11664510/b02f4cfca9b6/10.1177_20499361241308643-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd71/11664510/9cdbf82669f4/10.1177_20499361241308643-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd71/11664510/b02f4cfca9b6/10.1177_20499361241308643-fig2.jpg

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