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基于宏基因组下一代测序的成人重症社区获得性肺炎病因学:一项前瞻性多中心研究

Etiology of Severe Community-Acquired Pneumonia in Adults Based on Metagenomic Next-Generation Sequencing: A Prospective Multicenter Study.

作者信息

Wu Xiaodong, Li Yuanyuan, Zhang Ming, Li Miaomiao, Zhang Rong, Lu Xin, Gao Wei, Li Qin, Xia Yang, Pan Pinhua, Li Qiang

机构信息

Department of Respiratory and Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai, China.

Department of Respiratory Medicine (Department of Respiratory and Critical Care Medicine), National Key Clinical Specialty, Xiangya Hospital, Central South University, Changsha, China.

出版信息

Infect Dis Ther. 2020 Dec;9(4):1003-1015. doi: 10.1007/s40121-020-00353-y. Epub 2020 Nov 10.

Abstract

BACKGROUND

Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) has the potential to improve the pathogen identification in severe community-acquired pneumonia (SCAP).

METHODS

In this 1.5-year, multicenter, prospective study, we investigated the usefulness of mNGS of BALF for identifying pathogens of SCAP in hospitalized adults, comparing it with other laboratory methods.

RESULTS

Of 329 SCAP adults, a microbial etiology was established in 304 cases (92.4%). The overall microbial yield was 90.3% for mNGS versus 39.5% for other methods (P < 0.05). The most frequently detected pathogens in immunocompetent patients were Streptococcus pneumoniae (14.8%), rhinovirus (9.8%), Haemophilus influenzae (9.1%), Staphylococcus aureus (8.7%), and Chlamydia psittaci (8.0%), while in immunocompromised patients they were Pneumocystis jirovecii (44.6%), Klebsiella pneumoniae (18.5%), Streptococcus pneumoniae (15.4%), Haemophilus influenzae (13.8%), and Pseudomonas aeruginosa (13.8%). Notably, novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified from two patients solely by mNGS in January 2020; uncommon pathogens including Orientia tsutsugamushi and Nocardia otitidiscaviarum were identified from one patient, respectively. Furthermore, mixed infections were detected in 56.8% of the patients.

CONCLUSIONS

A high microbial detection rate was achieved in SCAP adults using mNGS testing of BALF. The most frequently detected pathogens of SCAP differed between immunocompetent and immunocompromised patients. mNGS testing may be an powerful tool for early identification of potential pathogens for SCAP to initiate a precise antimicrobial therapy.

摘要

背景

支气管肺泡灌洗液(BALF)的宏基因组下一代测序(mNGS)有潜力改善重症社区获得性肺炎(SCAP)的病原体鉴定。

方法

在这项为期1.5年的多中心前瞻性研究中,我们调查了BALF的mNGS在识别住院成人SCAP病原体方面的效用,并将其与其他实验室方法进行比较。

结果

在329例SCAP成人患者中,304例(92.4%)确定了微生物病因。mNGS的总体微生物检出率为90.3%,而其他方法为39.5%(P<0.05)。免疫功能正常患者中最常检测到的病原体是肺炎链球菌(14.8%)、鼻病毒(9.8%)、流感嗜血杆菌(9.1%)、金黄色葡萄球菌(8.7%)和鹦鹉热衣原体(8.0%),而在免疫功能低下患者中则是耶氏肺孢子菌(44.6%)、肺炎克雷伯菌(18.5%)、肺炎链球菌(15.4%)、流感嗜血杆菌(13.8%)和铜绿假单胞菌(13.8%)。值得注意的是,2020年1月仅通过mNGS从两名患者中鉴定出新型严重急性呼吸综合征冠状病毒2(SARS-CoV-2);分别从一名患者中鉴定出包括恙虫病东方体和鱼子酱诺卡菌在内的罕见病原体。此外,56.8%的患者检测到混合感染。

结论

使用BALF的mNGS检测在SCAP成人患者中实现了高微生物检出率。免疫功能正常和免疫功能低下患者中SCAP最常检测到的病原体有所不同。mNGS检测可能是早期识别SCAP潜在病原体以启动精确抗菌治疗的有力工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c8/7680495/b85de4cdda4e/40121_2020_353_Fig1_HTML.jpg

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