Effect of Metagenomic Next-Generation Sequencing on Clinical Outcomes of Patients With Severe Community-Acquired Pneumonia in the ICU: A Multicenter, Randomized Controlled Trial

Xiaojing Wu; Ting Sun; Hangyong He; Lihua Xing; Zhenshun Cheng; Shuang Geng; Dexiang Xu; Hong Luo; Cheng Chen; Mingyan Jiang; Guopeng Hou; Tianshu Zhai; Ying Cai; Yijie Liu; Junlu Li; Lan Ni; Xueying Li; Binbin Qu; Cheng Lei; Yang Wang; Zi Gu; Peng Zhang; Xu Huang; Min Li; Jingen Xia; Lian He; Qingyuan Zhan

doi:10.1016/j.chest.2024.07.144

Effect of Metagenomic Next-Generation Sequencing on Clinical Outcomes of Patients With Severe Community-Acquired Pneumonia in the ICU: A Multicenter, Randomized Controlled Trial

Chest. 2024 Jul 25:S0012-3692(24)04863-3. doi: 10.1016/j.chest.2024.07.144. Online ahead of print.

Authors

Xiaojing Wu¹, Ting Sun², Hangyong He³, Lihua Xing⁴, Zhenshun Cheng⁵, Shuang Geng⁶, Dexiang Xu⁷, Hong Luo⁸, Cheng Chen⁹, Mingyan Jiang¹⁰, Guopeng Hou¹¹, Tianshu Zhai³, Ying Cai³, Yijie Liu¹², Junlu Li⁴, Lan Ni⁵, Xueying Li⁶, Binbin Qu⁷, Cheng Lei⁸, Yang Wang⁹, Zi Gu¹⁰, Peng Zhang¹¹, Xu Huang³, Min Li³, Jingen Xia³, Lian He¹³, Qingyuan Zhan¹⁴

Affiliations

¹ National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing; Department of Respiratory and Critical Care Medicine, Beijing.
² The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang; Capital Medical University China-Japan Friendship School of Clinical Medicine, Beijing; Department of Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou.
³ National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing.
⁴ Binzhou Medical University Hospital, Binzhou; The Respiratory Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou.
⁵ Department of Respiratory and Critical Care Medicine, Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Zhongnan Hospital of Wuhan University.
⁶ Department of Respiratory and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.
⁷ Department of Pulmonary and Critical Care Medicine, The Affiliated Qingdao Central Hospital of Qingdao University, Qingdao.
⁸ Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha.
⁹ Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou.
¹⁰ Department of Pulmonary and Critical Care Medicine, Xiang Tan Central Hospital of Hunan Province, Xiangtan.
¹¹ Department of Pulmonary and Critical Care Medicine, The Third People's Hospital of Datong, Datong.
¹² Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing.
¹³ Department of Pulmonary and Critical Care Medicine, The Second People's Hospital of Guiyang, Guiyang, China.
¹⁴ National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing. Electronic address: drzhanqy@163.com.

PMID: 39067508
DOI: 10.1016/j.chest.2024.07.144

Abstract

Background: Metagenomic next-generation sequencing (mNGS) was previously established as a method that can increase the pathogen identification rate in patients with severe community-acquired pneumonia (SCAP).

Research question: What is the impact on clinical outcomes of mNGS of BAL fluid (BALF) in patients with SCAP in the ICU?

Study design and methods: A multicenter, randomized controlled, open-label clinical trial was conducted in 10 ICUs. Patients were randomized in a 1:1 ratio to undergo BALF assessment with conventional microbiological tests (CMTs) only (ie, the CMT group) or BALF assessment with both mNGS and CMTs (ie, the mNGS group). The primary outcome was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a six-category ordinal scale or discharge from the ICU, whichever occurred first.

Results: A total of 349 patients were randomized to treatment between January 1, 2021, and November 18, 2022; 170 were assigned to the CMT group and 179 to the mNGS group. In the intention-to-treat analysis, the time to clinical improvement was better in the mNGS group than in the CMT group (10 days vs 13 days; difference, -2.0 days; 95% CI, -3.0 to 0.0 days). Similar results were obtained in the per-protocol analysis. The proportion of patients with clinical improvement within 14 days was significantly higher in the mNGS group (62.0%) than in the CMT group (46.5%). There was no significant difference in other secondary outcomes.

Interpretation: Compared with the use of CMTs alone, mNGS combined with CMTs reduced the time to clinical improvement for patients with SCAP.

Clinical trial registration: ChiCTR2000037894.

Keywords: ICUs; clinical outcomes; metagenomic next-generation sequencing; severe community-acquired pneumonia.