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采用靶向二代测序检测法对疑似感染的成人血液系统恶性肿瘤患者进行病原体检测。

Pathogen detection by targeted next-generation sequencing test in adult hematological malignancies patients with suspected infections.

作者信息

Xu Jin-Hui, Cui Ya-Bin, Wang Li-Jie, Nan Hui-Jie, Yang Pei-Yao, Bai Yan-Liang, Shi Ming-Yue

机构信息

Department of Hematology, Zhengzhou University People's Hospital and Henan Provincial People's Hospital, Zhengzhou, China.

Department of Hematology, Henan University People's Hospital and Henan Provincial People's Hospital, Zhengzhou, China.

出版信息

Front Med (Lausanne). 2024 Sep 24;11:1443596. doi: 10.3389/fmed.2024.1443596. eCollection 2024.

DOI:10.3389/fmed.2024.1443596
PMID:39380735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11458473/
Abstract

BACKGROUND

Infections in patients with hematological malignancies (HM) are a significant cause of morbidity and mortality. Timely and effective empirical anti-infective treatment can reduce the infection-related mortality rate. Targeted next-generation sequencing (tNGS) offers a rapid diagnostic approach for identifying diverse pathogens in these patients. However, relevant research is still limited to adult patients with HM.

METHODS

We conducted a retrospective analysis of adult HM patients admitted to our hospital from March 2023 to September 2023, focusing on their clinical characteristics and the results of both tNGS and conventional microbiological tests (CMTs). We evaluated the performance of tNGS and CMTs in pathogenic diagnosis and described the distribution characteristics of pathogens in adult HM patients with infections.

RESULTS

The study included 209 samples collected from 137 patients. Results showed that the overall pathogen detection rate differed significantly between tNGS and CMTs (60.3% vs. 24.4%,  < 0.001). The sensitivity (69.7% vs. 35.9%), negative predictive value (NPV) (48.2% vs. 42.4%), and accuracy (66.5% vs. 56.5%) of pathogen detection were notably superior with tNGS compared to CMTs. Among the 142 samples with clinically diagnosed infections, tNGS combined with CMTs identified a definite or probable microbial etiology in 114 samples (80.3%). Of the 36 samples with concordant positive results from both tNGS and CMTs, 72.2% (26/36) exhibited full or partial agreement. Our study further showed the highest detection rate for viral infections (57.0%), predominantly for Epstein-Barr virus (DNA-V, 18.3%). Followed by bacterial infections (46.5%), the detection rate of Gram-negative bacteria (G, 35.9%) was higher than that of Gram-positive bacteria (G, 21.8%) in this study. (G, 12.7%) had the highest detection rate among these emerging bacteria, followed by (G, 10.6%) and (G, 7.7%). Bacterial-viral coinfections were the most common type of mixed infection (35.5%).

CONCLUSION

In conclusion, tNGS outperforms CMTs in both sensitivity and pathogen spectrum. Therefore, it can serve as an adjunct to CMTs to facilitate the precise adjustment of anti-infective regimens for adult HM patients. Our findings establish a basis for formulating empirical anti-infective therapy strategies tailored to the pathogen distribution in this patient population.

摘要

背景

血液系统恶性肿瘤(HM)患者的感染是发病和死亡的重要原因。及时有效的经验性抗感染治疗可降低感染相关死亡率。靶向新一代测序(tNGS)为识别这些患者中的多种病原体提供了一种快速诊断方法。然而,相关研究仍局限于成年HM患者。

方法

我们对2023年3月至2023年9月入住我院的成年HM患者进行了回顾性分析,重点关注其临床特征以及tNGS和传统微生物检测(CMT)的结果。我们评估了tNGS和CMT在病原诊断中的性能,并描述了成年感染HM患者中病原体的分布特征。

结果

该研究纳入了从137例患者中采集的209份样本。结果显示,tNGS和CMT的总体病原体检测率存在显著差异(60.3%对24.4%,<0.001)。与CMT相比,tNGS在病原体检测的敏感性(69.7%对35.9%)、阴性预测值(NPV)(48.2%对42.4%)和准确性(66.5%对56.5%)方面明显更优。在142例临床诊断为感染的样本中,tNGS与CMT联合在114例样本(80.3%)中确定了明确或可能的微生物病因。在tNGS和CMT结果均为阳性的36例样本中,72.2%(26/36)表现出完全或部分一致。我们的研究进一步显示病毒感染的检出率最高(57.0%),主要是EB病毒(DNA-V,18.3%)。其次是细菌感染(46.5%),本研究中革兰阴性菌(G,35.9%)的检出率高于革兰阳性菌(G,21.8%)。在这些新兴细菌中,(G,12.7%)的检出率最高,其次是(G,10.6%)和(G,7.7%)。细菌-病毒混合感染是最常见的混合感染类型(35.5%)。

结论

总之,tNGS在敏感性和病原体谱方面均优于CMT。因此,它可作为CMT的辅助手段,以促进成年HM患者抗感染方案的精确调整。我们的研究结果为制定针对该患者群体病原体分布的经验性抗感染治疗策略奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbd7/11458473/368929637607/fmed-11-1443596-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbd7/11458473/976836f3f816/fmed-11-1443596-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbd7/11458473/1da070a0a42f/fmed-11-1443596-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbd7/11458473/7e6d5d5d2f51/fmed-11-1443596-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbd7/11458473/368929637607/fmed-11-1443596-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbd7/11458473/976836f3f816/fmed-11-1443596-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbd7/11458473/1da070a0a42f/fmed-11-1443596-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbd7/11458473/7e6d5d5d2f51/fmed-11-1443596-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbd7/11458473/368929637607/fmed-11-1443596-g004.jpg

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