Blood transcriptomic discrimination of bacterial and viral infections in the emergency department: a multi-cohort observ
- PDF / 1,476,349 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 4 Downloads / 164 Views
RESEARCH ARTICLE
Open Access
Blood transcriptomic discrimination of bacterial and viral infections in the emergency department: a multi-cohort observational validation study Dayle Sampson1, Thomas D. Yager1, Brian Fox1, Laura Shallcross2, Leo McHugh1, Therese Seldon1, Antony Rapisarda1, Richard B. Brandon1, Krupa Navalkar1, Nandi Simpson3,4, Sian Stafford3, Eliza Gil3, Cristina Venturini3, Evi Tsaliki3, Jennifer Roe3, Benjamin Chain3 and Mahdad Noursadeghi3,4*
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. (Continued on next page)
* Correspondence: [email protected] 3 Division of Infection and Immunity, University College London, London, UK 4 National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, UK Full list of author information is available at the end of the article
© The Author(s). 2020 Open Access 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,
Data Loading...