eprintid: 10126777
rev_number: 18
eprint_status: archive
userid: 608
dir: disk0/10/12/67/77
datestamp: 2021-04-28 14:52:22
lastmod: 2021-12-02 23:16:23
status_changed: 2021-04-28 14:52:22
type: article
metadata_visibility: show
creators_name: Sampson, D
creators_name: Yager, TD
creators_name: Fox, B
creators_name: Shallcross, L
creators_name: McHugh, L
creators_name: Seldon, T
creators_name: Rapisarda, A
creators_name: Brandon, RB
creators_name: Navalkar, K
creators_name: Simpson, N
creators_name: Stafford, S
creators_name: Gil, E
creators_name: Venturini, C
creators_name: Tsaliki, E
creators_name: Roe, J
creators_name: Chain, B
creators_name: Noursadeghi, M
title: Blood transcriptomic discrimination of bacterial and viral infections in the emergency department: a multi-cohort observational validation study
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D15
divisions: DD4
divisions: D13
divisions: G24
divisions: B07
divisions: H17
keywords: Blood transcriptional profiling; Bacterial infection, viral infection; Emergency department
note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
abstract: Background: There is an urgent need to develop biomarkers that stratify risk of bacterial infection in order to support antimicrobial stewardship in emergency hospital admissions. / Methods: We used computational machine learning to derive a rule-out blood transcriptomic signature of bacterial infection (SeptiCyte™ TRIAGE) from eight published case-control studies. We then validated this signature by itself in independent case-control data from more than 1500 samples in total, and in combination with our previously published signature for viral infections (SeptiCyte™ VIRUS) using pooled data from a further 1088 samples. Finally, we tested the performance of these signatures in a prospective observational cohort of emergency department (ED) patients with fever, and we used the combined SeptiCyte™ signature in a mixture modelling approach to estimate the prevalence of bacterial and viral infections in febrile ED patients without microbiological diagnoses. / Results: 
The combination of SeptiCyte™ TRIAGE with our published signature for viral infections (SeptiCyte™ VIRUS) discriminated bacterial and viral infections in febrile ED patients, with a receiver operating characteristic area under the curve of 0.95 (95% confidence interval 0.90–1), compared to 0.79 (0.68–0.91) for WCC and 0.73 (0.61–0.86) for CRP. At pre-test probabilities 0.35 and 0.72, the combined SeptiCyte™ score achieved a negative predictive value for bacterial infection of 0.97 (0.90–0.99) and 0.86 (0.64–0.96), compared to 0.90 (0.80–0.94) and 0.66 (0.48–0.79) for WCC and 0.88 (0.69–0.95) and 0.60 (0.31–0.72) for CRP. In a mixture modelling approach, the combined SeptiCyte™ score estimated that 24% of febrile ED cases receiving antibacterials without a microbiological diagnosis were due to viral infections. Our analysis also suggested that a proportion of patients with bacterial infection recovered without antibacterials. / Conclusions: Blood transcriptional biomarkers offer exciting opportunities to support precision antibacterial prescribing in ED and improve diagnostic classification of patients without microbiologically confirmed infections.
date: 2020-07-21
date_type: published
publisher: BMC
official_url: https://doi.org/10.1186/s12916-020-01653-3
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1800471
doi: 10.1186/s12916-020-01653-3
lyricists_name: Chain, Benjamin
lyricists_name: Noursadeghi, Mahdad
lyricists_name: Shallcross, Laura
lyricists_name: Tsaliki, Evdokia
lyricists_name: Venturini, Cristina
lyricists_id: BMCHA43
lyricists_id: MNOUR10
lyricists_id: LSHAL65
lyricists_id: ETSAL09
lyricists_id: CVENT62
actors_name: Zahnhausen-Stuber, Petra
actors_id: PMZAH20
actors_role: owner
full_text_status: public
publication: BMC Medicine
volume: 18
number: 1
pages: 12
issn: 1741-7015
citation:        Sampson, D;    Yager, TD;    Fox, B;    Shallcross, L;    McHugh, L;    Seldon, T;    Rapisarda, A;                                         ... Noursadeghi, M; + view all <#>        Sampson, D;  Yager, TD;  Fox, B;  Shallcross, L;  McHugh, L;  Seldon, T;  Rapisarda, A;  Brandon, RB;  Navalkar, K;  Simpson, N;  Stafford, S;  Gil, E;  Venturini, C;  Tsaliki, E;  Roe, J;  Chain, B;  Noursadeghi, M;   - view fewer <#>    (2020)    Blood transcriptomic discrimination of bacterial and viral infections in the emergency department: a multi-cohort observational validation study.                   BMC Medicine , 18  (1)      10.1186/s12916-020-01653-3 <https://doi.org/10.1186/s12916-020-01653-3>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10126777/1/Blood%20transcriptomic%20discrimination%20of%20bacterial%20and%20viral%20infections%20in%20the%20emergency%20department%20a%20multi-cohort%20observation.pdf