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      Risk Factors and Outcome of Sepsis in Traumatic Patients and Pathogen Detection Using Metagenomic Next-Generation Sequencing

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          Abstract

          Objective

          Sepsis, a life-threatening clinical syndrome, is a leading cause of mortality after experiencing multiple traumas. Once diagnosed with sepsis, patients should be given an appropriate empiric antimicrobial treatment followed by the specific antibiotic therapy based on blood culture due to its rapid progression to tissue damage and organ failure. In this study, we aimed to analyze the risk factors and outcome of sepsis in traumatic patients and to investigate the performance of metagenomic next-generation sequencing (mNGS) compared with standard microbiological diagnostics in post-traumatic sepsis.

          Methods

          The study included 528 patients with multiple traumas among which there were 142 cases with post-traumatic sepsis. Patients' demographic and clinical data were recorded. The outcome measures included mortality during the emergency intensive care unit (EICU), EICU length of stay (LOS), all-cause 28-day mortality, and total ventilator days in 28 days after admission. A total of 89 blood samples from 89 septic patients underwent standard microbiological blood cultures and 89 samples of peripheral blood ( n = 21), wound secretion ( n = 41), bronchoalveolar lavage fluid (BALF) (19), ascites ( n = 5), and sputum ( n = 3) underwent mNGS. Pathogen detection was compared between standard microbiological blood cultures and mNGS.

          Results

          The sepsis group and non-sepsis group exhibited significant differences regarding shock on admission, blood transfusion, mechanical ventilation, body temperature, heart rate, WBC count, neutrophil count, hematocrit, urea nitrogen, creatinine, CRP, D-D dimer, PCT, scores of APACHE II, sequential organ failure assessment (SOFA), and Injury Severity Score (ISS) on admission to the EICU, and Multiple Organ Dysfunction Syndromes (MODS) ( P < 0.05). Multivariate logistic regression analysis showed that scores of APACHE II, SOFA, and ISS on admission, and MODS were independent risk factors for the occurrence of sepsis in patients with multiple traumas. The 28-day mortality was higher in the sepsis group than in the non-sepsis group (45.07% vs. 19.17%, P < 0.001). The mortality during the EICU was higher in the sepsis group than in the non-sepsis group ( P=0.002). The LOS in the EICU in the sepsis group was increased compared with the non-sepsis group ( P=0.004). The total ventilator days in 28 days after admission in the sepsis group was increased compared with the non-sepsis group ( P < 0.001). Multivariate logistic regression analysis showed that septic shock, APACHE II score on admission, SOFA score, and MODS were independent risk factors of death for patients with post-traumatic sepsis. The positive detection rate of mNGS was 91.01% (81/89), which was significantly higher than that of standard microbiological blood cultures (39.33% (35/89)). Standard microbiological blood cultures and mNGS methods demonstrated double positive results in 33 (37.08%) specimens and double-negative results in 8 (8.99%) specimens, while 46 (51.69%) samples and 2 (2.25%) samples had positive results only with mNGS or culture alone, respectively.

          Conclusion

          Our study identifies risk factors for the incidence and death of sepsis in traumatic patients and shows that mNGS may serve as a better diagnostic tool for the identification of pathogens in post-traumatic sepsis than standard microbiological blood cultures.

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          Most cited references46

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          The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

          Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
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            Clinical metagenomics

            Clinical metagenomic next-generation sequencing (mNGS), the comprehensive analysis of microbial and host genetic material (DNA and RNA) in samples from patients, is rapidly moving from research to clinical laboratories. This emerging approach is changing how physicians diagnose and treat infectious disease, with applications spanning a wide range of areas, including antimicrobial resistance, the microbiome, human host gene expression (transcriptomics) and oncology. Here, we focus on the challenges of implementing mNGS in the clinical laboratory and address potential solutions for maximizing its impact on patient care and public health.
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              Clinical Metagenomic Next-Generation Sequencing for Pathogen Detection

              Nearly all infectious agents contain DNA or RNA genomes, making sequencing an attractive approach for pathogen detection. The cost of high-throughput or next-generation sequencing has been reduced by several orders of magnitude since its advent in 2004, and it has emerged as an enabling technological platform for the detection and taxonomic characterization of microorganisms in clinical samples from patients. This review focuses on the application of untargeted metagenomic next-generation sequencing to the clinical diagnosis of infectious diseases, particularly in areas in which conventional diagnostic approaches have limitations. The review covers ( a) next-generation sequencing technologies and common platforms, ( b) next-generation sequencing assay workflows in the clinical microbiology laboratory, ( c) bioinformatics analysis of metagenomic next-generation sequencing data, ( d) validation and use of metagenomic next-generation sequencing for diagnosing infectious diseases, and ( e) significant case reports and studies in this area. Next-generation sequencing is a new technology that has the promise to enhance our ability to diagnose, interrogate, and track infectious diseases.
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                Author and article information

                Contributors
                Journal
                Can J Infect Dis Med Microbiol
                Can J Infect Dis Med Microbiol
                CJIDMM
                The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien des Maladies Infectieuses et de la Microbiologie Médicale
                Hindawi
                1712-9532
                1918-1493
                2022
                25 April 2022
                : 2022
                : 2549413
                Affiliations
                Department of Emergency Medicine, Shanghai Jiao Tong University, Affiliated Sixth People' Hospital, Shanghai, China
                Author notes

                Academic Editor: Mohd Adnan

                Author information
                https://orcid.org/0000-0003-3612-4008
                Article
                10.1155/2022/2549413
                9061056
                35509518
                a4a120e9-861b-4e7d-8d4a-5628c18f5b7a
                Copyright © 2022 Yiqing Tong et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 January 2022
                : 16 March 2022
                : 6 April 2022
                Funding
                Funded by: Science Research Project in Hospital
                Award ID: ynhg202107
                Funded by: Clinical Research Plan of SHDC
                Award ID: SHDC2020CR6030
                Categories
                Research Article

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