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.
Journal
Critical care medicine
ISSN: 1530-0293
Titre abrégé: Crit Care Med
Pays: United States
ID NLM: 0355501
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
pubmed:
25
6
2021
medline:
5
10
2021
entrez:
24
6
2021
Statut:
ppublish
Résumé
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. Prospective observational study. Emergency Department, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany. Three hundred twelve adult patients presenting to the emergency department with suspected acute infections or sepsis with at least one vital sign change. None (observational study only). 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). 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.
Identifiants
pubmed: 34166284
doi: 10.1097/CCM.0000000000005119
pii: 00003246-202110000-00006
pmc: PMC8439671
doi:
Substances chimiques
Biomarkers
0
RNA, Messenger
0
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1664-1673Commentaires et corrections
Type : CommentIn
Informations de copyright
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.
Références
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