Impact of metagenomics next-generation sequencing on etiological diagnosis and early outcomes in sepsis
Abstract Background Clinical implications of metagenomics next-generation sequencing (mNGS) in sepsis have not been fully evaluated. This study aimed to determine the diagnostic, therapeutic, and prognostic impacts of mNGS in sepsis. Methods This multicenter prospective study was conducted at 19 sit...
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2025-04-01
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| Online Access: | https://doi.org/10.1186/s12967-025-06332-6 |
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| author | Feixiang Xu Chen Chen Su Lu Mingming Xue Hailin Ding Yanli Song Yun Zhang Keyu Sun Lunxian Tang Wei Wang Meitang Wang Yan Tang Dingyu Tan Chenling Yao Dongwei Shi Enqiang Mao Mian Shao Youguo Ying Chunmei Zhou Lihong Huang Hu Peng Zhongshu Kuang Sanqiang Wang Qingbian Ma Si Sun Dongfeng Guo Tianwen Gu Bin Yang Linhao Ma Chengjin Gao Xiaoye Lu Hong Zhang Ruilan Wang Chaoyang Tong Zhenju Song |
| author_facet | Feixiang Xu Chen Chen Su Lu Mingming Xue Hailin Ding Yanli Song Yun Zhang Keyu Sun Lunxian Tang Wei Wang Meitang Wang Yan Tang Dingyu Tan Chenling Yao Dongwei Shi Enqiang Mao Mian Shao Youguo Ying Chunmei Zhou Lihong Huang Hu Peng Zhongshu Kuang Sanqiang Wang Qingbian Ma Si Sun Dongfeng Guo Tianwen Gu Bin Yang Linhao Ma Chengjin Gao Xiaoye Lu Hong Zhang Ruilan Wang Chaoyang Tong Zhenju Song |
| author_sort | Feixiang Xu |
| collection | DOAJ |
| description | Abstract Background Clinical implications of metagenomics next-generation sequencing (mNGS) in sepsis have not been fully evaluated. This study aimed to determine the diagnostic, therapeutic, and prognostic impacts of mNGS in sepsis. Methods This multicenter prospective study was conducted at 19 sites in China from 2020 to 2021, and 859 adult patients hospitalized with sepsis were enrolled. The advantages, challenges, knowledge gaps and privacy risks of mNGS were carefully introduced to all participants, and participants chose on their own to either receive conventional microbiological test (CMT) alone (conventional-test-only group, n = 394) or receive mNGS test along with CMT (combined test group, n = 465). For prognostic analysis, the primary endpoint was 28-day mortality. Secondary endpoints included 7-day mortality and average per-day hospital cost. Inverse probability of treatment weighting was used to balance covariates between groups. Concurrent CMT and mNGS results from patients in the combined test group were used for diagnostic analyses. Therapeutic impact of mNGS was evaluated based on subsequent antibiotic adjustment. Results Compared with composite reference standard, the positive percent agreement of mNGS among infected site samples was significantly higher than that of CMT (92.0% [95% CI, 88.7 to 94.5] vs. 51.1% [95% CI, 45.9 to 56.2], p < 0.001), while the negative percent agreement of mNGS was inferior to that of CMT (39.6% [95% CI, 29.5 to 50.4] vs. 69.2% [95% CI, 58.7 to 78.5], p < 0.001). The mNGS test identified causal microbes in 344 (74.0%) patients, and concomitant antibiotic changes occurred in 136 patients (29.2%). Death by day 7 occurred in 24 of 465 (5.2%) patients in the combined test group and in 34 of 394 (8.6%) patients in the conventional-test-only group (hazard ratio, 0.44 [95% CI, 0.26 to 0.77], p = 0.004). However, no significant difference in 28-day mortality was observed between two study groups (hazard ratio, 0.82 [0.56 to 1.20], p = 0.300). Conclusions The mNGS test of infected site samples exhibited 40% higher pathogen detection rate than CMT in patients with sepsis, which led to improved etiological diagnosis and tailored antibiotic therapy. Additional use of mNGS halved the risk of early death in 7 days, but did not improve 28-day survival in patients with sepsis. Trial registration chictr.org.cn Identifier: ChiCTR2000031113. Registered 22 March 2020. |
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| institution | DOAJ |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj-art-741d46aef24d4443a4a52b9717ce1af42025-08-20T03:07:44ZengBMCJournal of Translational Medicine1479-58762025-04-0123111210.1186/s12967-025-06332-6Impact of metagenomics next-generation sequencing on etiological diagnosis and early outcomes in sepsisFeixiang Xu0Chen Chen1Su Lu2Mingming Xue3Hailin Ding4Yanli Song5Yun Zhang6Keyu Sun7Lunxian Tang8Wei Wang9Meitang Wang10Yan Tang11Dingyu Tan12Chenling Yao13Dongwei Shi14Enqiang Mao15Mian Shao16Youguo Ying17Chunmei Zhou18Lihong Huang19Hu Peng20Zhongshu Kuang21Sanqiang Wang22Qingbian Ma23Si Sun24Dongfeng Guo25Tianwen Gu26Bin Yang27Linhao Ma28Chengjin Gao29Xiaoye Lu30Hong Zhang31Ruilan Wang32Chaoyang Tong33Zhenju Song34Department of Emergency, Zhongshan Hospital, Fudan UniversityDepartment of Emergency, Zhongshan Hospital, Fudan UniversityDepartment of Emergency, Zhongshan Hospital, Fudan UniversityDepartment of Emergency, Zhongshan Hospital, Fudan UniversityDepartment of Emergency, Zhongshan Hospital, Fudan UniversityDepartment of Emergency Internal Medicine, Tongji Hospital, Tongji UniversityDepartment of Emergency Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical UniversityDepartment of Emergency, Minhang Hospital, Fudan UniversityDepartment of Emergency Medicine and Critical Care, East Hospital, Tongji UniversityDepartment of Emergency, Shanghai Xuhui Central HospitalEmergency Department, Changhai Hospital, Navy Medical UniversityDepartment of Emergency, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan UniversityDepartment of Emergency, Northern Jiangsu People’s Hospital, Yangzhou UniversityDepartment of Emergency, Zhongshan Hospital, Fudan UniversityDepartment of Emergency, Zhongshan Hospital, Fudan UniversityDepartment of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Emergency, Zhongshan Hospital, Fudan UniversityEmergency Department, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Clinical Microbiology Laboratory, Zhongshan Hospital, Fudan UniversityDepartment of Biostatistics, Zhongshan Hospital, Fudan UniversityDepartment of Emergency, Shanghai Tenth People’s Hospital, Tongji UniversityDepartment of Emergency, Zhongshan Hospital, Fudan UniversityDepartment of Emergency, Zhongshan Hospital, Fudan UniversityEmergency Department, Peking University Third HospitalDepartment of Emergency, Zhongshan Hospital, Fudan UniversityDepartment of Emergency Medicine, Gongli HospitalDepartment of Emergency, Zhongshan Hospital, Fudan UniversityVision Medicals Center for Infectious DiseasesDepartment of Emergency and Critical Care Medicine, Shanghai Changzheng Hospital, Naval Medical UniversityDepartment of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Emergency, Renji Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Emergency Medicine, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Emergency and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Emergency, Zhongshan Hospital, Fudan UniversityDepartment of Emergency, Zhongshan Hospital, Fudan UniversityAbstract Background Clinical implications of metagenomics next-generation sequencing (mNGS) in sepsis have not been fully evaluated. This study aimed to determine the diagnostic, therapeutic, and prognostic impacts of mNGS in sepsis. Methods This multicenter prospective study was conducted at 19 sites in China from 2020 to 2021, and 859 adult patients hospitalized with sepsis were enrolled. The advantages, challenges, knowledge gaps and privacy risks of mNGS were carefully introduced to all participants, and participants chose on their own to either receive conventional microbiological test (CMT) alone (conventional-test-only group, n = 394) or receive mNGS test along with CMT (combined test group, n = 465). For prognostic analysis, the primary endpoint was 28-day mortality. Secondary endpoints included 7-day mortality and average per-day hospital cost. Inverse probability of treatment weighting was used to balance covariates between groups. Concurrent CMT and mNGS results from patients in the combined test group were used for diagnostic analyses. Therapeutic impact of mNGS was evaluated based on subsequent antibiotic adjustment. Results Compared with composite reference standard, the positive percent agreement of mNGS among infected site samples was significantly higher than that of CMT (92.0% [95% CI, 88.7 to 94.5] vs. 51.1% [95% CI, 45.9 to 56.2], p < 0.001), while the negative percent agreement of mNGS was inferior to that of CMT (39.6% [95% CI, 29.5 to 50.4] vs. 69.2% [95% CI, 58.7 to 78.5], p < 0.001). The mNGS test identified causal microbes in 344 (74.0%) patients, and concomitant antibiotic changes occurred in 136 patients (29.2%). Death by day 7 occurred in 24 of 465 (5.2%) patients in the combined test group and in 34 of 394 (8.6%) patients in the conventional-test-only group (hazard ratio, 0.44 [95% CI, 0.26 to 0.77], p = 0.004). However, no significant difference in 28-day mortality was observed between two study groups (hazard ratio, 0.82 [0.56 to 1.20], p = 0.300). Conclusions The mNGS test of infected site samples exhibited 40% higher pathogen detection rate than CMT in patients with sepsis, which led to improved etiological diagnosis and tailored antibiotic therapy. Additional use of mNGS halved the risk of early death in 7 days, but did not improve 28-day survival in patients with sepsis. Trial registration chictr.org.cn Identifier: ChiCTR2000031113. Registered 22 March 2020.https://doi.org/10.1186/s12967-025-06332-6SepsisMetagenomics next-generation sequencingConventional microbiological testEtiological diagnosisAntibiotics28-day mortality |
| spellingShingle | Feixiang Xu Chen Chen Su Lu Mingming Xue Hailin Ding Yanli Song Yun Zhang Keyu Sun Lunxian Tang Wei Wang Meitang Wang Yan Tang Dingyu Tan Chenling Yao Dongwei Shi Enqiang Mao Mian Shao Youguo Ying Chunmei Zhou Lihong Huang Hu Peng Zhongshu Kuang Sanqiang Wang Qingbian Ma Si Sun Dongfeng Guo Tianwen Gu Bin Yang Linhao Ma Chengjin Gao Xiaoye Lu Hong Zhang Ruilan Wang Chaoyang Tong Zhenju Song Impact of metagenomics next-generation sequencing on etiological diagnosis and early outcomes in sepsis Journal of Translational Medicine Sepsis Metagenomics next-generation sequencing Conventional microbiological test Etiological diagnosis Antibiotics 28-day mortality |
| title | Impact of metagenomics next-generation sequencing on etiological diagnosis and early outcomes in sepsis |
| title_full | Impact of metagenomics next-generation sequencing on etiological diagnosis and early outcomes in sepsis |
| title_fullStr | Impact of metagenomics next-generation sequencing on etiological diagnosis and early outcomes in sepsis |
| title_full_unstemmed | Impact of metagenomics next-generation sequencing on etiological diagnosis and early outcomes in sepsis |
| title_short | Impact of metagenomics next-generation sequencing on etiological diagnosis and early outcomes in sepsis |
| title_sort | impact of metagenomics next generation sequencing on etiological diagnosis and early outcomes in sepsis |
| topic | Sepsis Metagenomics next-generation sequencing Conventional microbiological test Etiological diagnosis Antibiotics 28-day mortality |
| url | https://doi.org/10.1186/s12967-025-06332-6 |
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