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Tytuł pozycji:

A Novel 29-Messenger RNA Host-Response Assay From Whole Blood Accurately Identifies Bacterial and Viral Infections in Patients Presenting to the Emergency Department With Suspected Infections: A Prospective Observational Study.

Tytuł:
A Novel 29-Messenger RNA Host-Response Assay From Whole Blood Accurately Identifies Bacterial and Viral Infections in Patients Presenting to the Emergency Department With Suspected Infections: A Prospective Observational Study.
Autorzy:
Bauer W; Department of Emergency Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany.
Kappert K; Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Berlin, Germany.
Galtung N; Department of Emergency Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany.
Lehmann D; Department of Emergency Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany.
Wacker J; Inflammatix, Burlingame, CA.
Cheng HK; Inflammatix, Burlingame, CA.
Liesenfeld O; Inflammatix, Burlingame, CA.
Buturovic L; Inflammatix, Burlingame, CA.
Luethy R; Inflammatix, Burlingame, CA.
Sweeney TE; Inflammatix, Burlingame, CA.
Tauber R; Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Berlin, Germany.
Somasundaram R; Department of Emergency Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany.
Źródło:
Critical care medicine [Crit Care Med] 2021 Oct 01; Vol. 49 (10), pp. 1664-1673.
Typ publikacji:
Journal Article; Observational Study
Język:
English
Imprint Name(s):
Publication: Philadelphia, PA : Lippincott Williams & Wilkins
Original Publication: New York, Kolen.
MeSH Terms:
Bacterial Infections/*diagnosis
RNA, Messenger/*analysis
Virus Diseases/*diagnosis
Aged ; Aged, 80 and over ; Area Under Curve ; Bacterial Infections/blood ; Bacterial Infections/physiopathology ; Berlin ; Biomarkers/analysis ; Biomarkers/blood ; Emergency Service, Hospital/organization & administration ; Emergency Service, Hospital/statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; RNA, Messenger/blood ; ROC Curve ; Virus Diseases/blood ; Virus Diseases/physiopathology
References:
Álvaro-Meca A, Jiménez-Sousa MA, Micheloud D, et al.; Group of Biomedical Research in Critical Care Medicine (BioCritic): Epidemiological trends of sepsis in the twenty-first century (2000-2013): An analysis of incidence, mortality, and associated costs in Spain. Popul Health Metr. 2018; 16:4.
Rhodes A, Evans LE, Alhazzani W, et al.: Surviving sepsis campaign: International guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017; 45:486–552.
Seymour CW, Gesten F, Prescott HC, et al.: Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017; 376:2235–2244.
Sweeney TE, Shidham A, Wong HR, et al.: A comprehensive time-course-based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set. Sci Transl Med. 2015; 7:287ra71.
Sweeney TE, Liesenfeld O, May L: Diagnosis of bacterial sepsis: Why are tests for bacteremia not sufficient? Expert Rev Mol Diagn. 2019; 19:959–962.
Sweeney TE, Wong HR, Khatri P: Robust classification of bacterial and viral infections via integrated host gene expression diagnostics. Sci Transl Med. 2016; 8:346ra91.
Sweeney TE, Perumal TM, Henao R, et al.: Mortality prediction in sepsis via gene expression analysis: A community approach. bioRxiv. 095489.
Sweeney TE, Khatri P: Benchmarking sepsis gene expression diagnostics using public data. Crit Care Med. 2017; 45:1–10.
Mayhew MB, Buturovic L, Luethy R, et al.: A generalizable 29-mRNA neural-network classifier for acute bacterial and viral infections. Nat Commun. 2020; 11:1177.
Huang DT, Yealy DM, Filbin MR, et al.; ProACT Investigators: Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N Engl J Med. 2018; 379:236–249.
Hamade B, Huang DT: Procalcitonin: Where are we now? Crit Care Clin. 2020; 36:23–40.
Goodlet KJ, Cameron EA, Nailor MD: Low sensitivity of procalcitonin for bacteremia at an academic medical center: A cautionary tale for antimicrobial stewardship. Open Forum Infect Dis. 2020; 7:ofaa096.
Schuetz P, Christ-Crain M, Thomann R, et al.; ProHOSP Study Group: Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: The ProHOSP randomized controlled trial. JAMA. 2009; 302:1059–1066.
Shapiro NI, Self WH, Rosen J, et al.: A prospective, multi-centre US clinical trial to determine accuracy of FebriDx point-of-care testing for acute upper respiratory infections with and without a confirmed fever. Ann Med. 2018; 50:420–429.
van Houten CB, de Groot JAH, Klein A, et al.: A host-protein based assay to differentiate between bacterial and viral infections in preschool children (OPPORTUNITY): A double-blind, multicentre, validation study. Lancet Infect Dis. 2017; 17:431–440.
Self WH, Rosen J, Sharp SC, et al.: Diagnostic accuracy of FebriDx: A rapid test to detect immune responses to viral and bacterial upper respiratory infections. J Clin Med. 2017; 6:E94.
Srugo I, Klein A, Stein M, et al.: Validation of a novel assay to distinguish bacterial and viral infections. Pediatrics. 2017; 140:e20163453.
Singer M, Inada-Kim M, Shankar-Hari M: Sepsis hysteria: Excess hype and unrealistic expectations. Lancet. 2019; 394:1513–1514.
Mi MY, Klompas M, Evans L: Early Administration of antibiotics for suspected sepsis. N Engl J Med. 2019; 380:593–596.
Substance Nomenclature:
0 (Biomarkers)
0 (RNA, Messenger)
Entry Date(s):
Date Created: 20210624 Date Completed: 20211004 Latest Revision: 20230812
Update Code:
20240105
PubMed Central ID:
PMC8439671
DOI:
10.1097/CCM.0000000000005119
PMID:
34166284
Czasopismo naukowe
Objectives: The rapid diagnosis of acute infections and sepsis remains a serious challenge. As a result of limitations in current diagnostics, guidelines recommend early antimicrobials for suspected sepsis patients to improve outcomes at a cost to antimicrobial stewardship. We aimed to develop and prospectively validate a new, 29-messenger RNA blood-based host-response classifier Inflammatix Bacterial Viral Non-Infected version 2 (IMX-BVN-2) to determine the likelihood of bacterial and viral infections.
Design: Prospective observational study.
Setting: Emergency Department, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany.
Patients: Three hundred twelve adult patients presenting to the emergency department with suspected acute infections or sepsis with at least one vital sign change.
Interventions: None (observational study only).
Measurements and Main Results: Gene expression levels from extracted whole blood RNA was quantified on a NanoString nCounter SPRINT (NanoString Technologies, Seattle, WA). Two predicted probability scores for the presence of bacterial and viral infection were calculated using the IMX-BVN-2 neural network classifier, which was trained on an independent development set. The IMX-BVN-2 bacterial score showed an area under the receiver operating curve for adjudicated bacterial versus ruled out bacterial infection of 0.90 (95% CI, 0.85-0.95) compared with 0.89 (95% CI, 0.84-0.94) for procalcitonin with procalcitonin being used in the adjudication. The IMX-BVN-2 viral score area under the receiver operating curve for adjudicated versus ruled out viral infection was 0.83 (95% CI, 0.77-0.89).
Conclusions: IMX-BVN-2 demonstrated accuracy for detecting both viral infections and bacterial infections. This shows the potential of host-response tests as a novel and practical approach for determining the causes of infections, which could improve patient outcomes while upholding antimicrobial stewardship.
(Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)
Comment in: Crit Care Med. 2021 Oct 1;49(10):1812-1814. (PMID: 34529611)

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