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宏基因组下一代测序在检测下呼吸道感染病原体中的临床应用

Clinical utility of metagenomic next-generation sequencing in pathogen detection for lower respiratory tract infections.

作者信息

Lai Lan Min, Dai Qian-Bing, Cao Mei Ling, Liu Yang, Zhao Rui, Yuan Lei

机构信息

Department of Clinical laboratory, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17, YongWaiZhengStreet, Nanchang, 330006, China.

出版信息

Sci Rep. 2025 May 30;15(1):19039. doi: 10.1038/s41598-025-03564-w.

Abstract

Identifying pathogens in patients with lower respiratory tract infections (LRTIs) has always been a major challenge. Metagenomic next-generation sequencing (mNGS) technology is a new diagnostic tool that can assist clinicians in the etiological diagnosis of LRTIs. This study focuses on the clinical value of mNGS in the diagnosis of suspected LRTIs. A total of 400 patients with suspected LRTIs admitted at the First Affiliated Hospital of Nanchang University from July 2020 to February 2023 were enrolled in this retrospective study. Bronchoalveolar lavage fluid (BALF) samples were analyzed using both mNGS and culture methods. The diagnostic accuracy of two approaches was systematically compared against the final clinical diagnosis, which served as the gold-standard reference. Of the 400 enrolled cases, 82.3% (329/400) were diagnosed with LRTIs. From these cases, mNGS identified 76.8% (307/400) truepositive cases, 8.0% (32/400) falsepositive cases, 9.8% (39/400) truenegative cases, and 5.5% (22/400) falsenegative cases. mNGS demonstrated significantly higher sensitivity [93.3% (307/329) vs. 55.6(183/329)%] alongside greater negative predictive values [63.9% (39/61) vs.25.9%(51/197)], whereas culture offered higher specificity [54.9%(39/71) vs. 71.8%(51/71)]. The area under the receiver-operating curve (AUC) of mNGS[0.744(95%CI: 0.67-0.82)]was significantly higher than that of cultures[0.636(95%CI: 0.57-0.71)]. Specifically, mNGS detected more Streptococcus pneumoniae (7.0% vs. 0%), Haemophilus influenzae (6.7% vs. 0%), Aspergillus (9.4% vs. 3.5%), Pneumocystis jirovecii (11.9% vs. 0%) and other intracellular pathogens. Of the 329 patients with LRTIs, antibiotic treatment was modified based on the mNGS results in more than half of the patients(50.5%,166/329), including 20 cases of adjusted antimicrobial regimens, 70 cases de-escalated the empirical antibiotic treatment, and 76 patients escalated the treatment by increasing dosage or medication. 60.8%(101/166) of patients responded to modified antibiotic treatment. Significant benefits of mNGS have been shown in pathogen identification and antimicrobial treatment stewardship in patients with LRTIs. For those with suboptimal therapeutic responses, physicians should be alert to some emerging intracellular pathogens, including Chlamydia psittaci, Mycobacterium tuberculosis, and Pneumocystis jirovecii.

摘要

识别下呼吸道感染(LRTIs)患者的病原体一直是一项重大挑战。宏基因组下一代测序(mNGS)技术是一种新的诊断工具,可协助临床医生对LRTIs进行病因诊断。本研究聚焦于mNGS在疑似LRTIs诊断中的临床价值。本项回顾性研究纳入了2020年7月至2023年2月在南昌大学第一附属医院收治的400例疑似LRTIs患者。采用mNGS和培养方法对支气管肺泡灌洗液(BALF)样本进行分析。将两种方法的诊断准确性与作为金标准参考的最终临床诊断进行系统比较。在400例纳入病例中,82.3%(329/400)被诊断为LRTIs。在这些病例中,mNGS识别出76.8%(307/400)的真阳性病例、8.0%(32/400)的假阳性病例、9.8%(39/400)的真阴性病例和5.5%(22/400)的假阴性病例。mNGS显示出显著更高的敏感性[93.3%(307/329)对55.6%(183/329)]以及更高的阴性预测值[63.9%(39/61)对25.9%(51/197)],而培养法具有更高的特异性[54.9%(39/71)对71.8%(51/71)]。mNGS的受试者工作特征曲线(AUC)面积[0.744(95%CI:0.67 - 0.82)]显著高于培养法[0.636(95%CI:0.57 - 0.71)]。具体而言,mNGS检测到更多的肺炎链球菌(7.0%对0%)、流感嗜血杆菌(6.7%对0%)、曲霉(9.4%对3.5%)、耶氏肺孢子菌(11.9%对0%)和其他细胞内病原体。在329例LRTIs患者中,超过半数(50.5%,166/329)的患者根据mNGS结果调整了抗生素治疗,其中20例调整了抗菌方案,70例降低了经验性抗生素治疗级别,76例通过增加剂量或用药升级了治疗。60.8%(101/166)的患者对调整后的抗生素治疗有反应。mNGS在LRTIs患者的病原体识别和抗菌治疗管理方面已显示出显著益处。对于治疗反应欠佳的患者,医生应警惕一些新出现的细胞内病原体,包括鹦鹉热衣原体、结核分枝杆菌和耶氏肺孢子菌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5923/12125369/8ba23999792f/41598_2025_3564_Fig1_HTML.jpg

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