Pathogen-specific host response in critically ill patients with blood stream infections: a nested case–control study
1
Issued Date
2025-07-01
Resource Type
eISSN
23523964
Scopus ID
2-s2.0-105007851880
Journal Title
Ebiomedicine
Volume
117
Rights Holder(s)
SCOPUS
Bibliographic Citation
Ebiomedicine Vol.117 (2025)
Suggested Citation
Butler J.M., Peters-Sengers H., Reijnders T.D.Y., van Engelen T.S.R., Uhel F., van Vught L.A., Schultz M.J., Laterre P.F., François B., Sánchez-García M., Lombardo E., Sweeney T.E., Bonten M.J., Wiersinga W.J., Sampson D., Bolero L.C., Yager T., Cremer O.L., Scicluna B.P., van der Poll T. Pathogen-specific host response in critically ill patients with blood stream infections: a nested case–control study. Ebiomedicine Vol.117 (2025). doi:10.1016/j.ebiom.2025.105799 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/110770
Title
Pathogen-specific host response in critically ill patients with blood stream infections: a nested case–control study
Author's Affiliation
Cliniques Universitaires Saint-Luc
Mahidol Oxford Tropical Medicine Research Unit
Cell Therapy Technology Center
Inflammatix Inc.
Hospital Clínico San Carlos
Al Biostats
Elysium Health
L-Università ta' Malta
Amsterdam UMC - University of Amsterdam
Amsterdam institute for Infection and Immunity
University Medical Center Utrecht
CHU de Limoges
Nuffield Department of Medicine
Mahidol Oxford Tropical Medicine Research Unit
Cell Therapy Technology Center
Inflammatix Inc.
Hospital Clínico San Carlos
Al Biostats
Elysium Health
L-Università ta' Malta
Amsterdam UMC - University of Amsterdam
Amsterdam institute for Infection and Immunity
University Medical Center Utrecht
CHU de Limoges
Nuffield Department of Medicine
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Knowledge of the contribution of the pathogen to the heterogeneity of the host response to infection is limited. We aimed to compare the host response in critically ill patients with a bloodstream infection (BSI). Methods: RNA profiles were determined in blood obtained between one day before and after a positive blood culture. Differential expression and pathway analyses were performed on independent patients’ samples by RNA sequencing (discovery) or microarray (validation). Additional patients were included for the discovery and validation of transcriptome classifiers of pathogen-specific BSIs. Twenty biomarkers reflecting key host response pathways were measured in blood. Findings: We included 341 patients, among which 255 with BSI, 25 with viral infection and 61 non-infectious controls. The cultured pathogen explained 41·8% of the blood transcriptomic variance in patients with BSI. Gene set enrichment analysis showed a global resemblance between monomicrobial BSIs caused by Streptococcus, Staphylococcus aureus and Escherichia coli, which were clearly different from BSI caused by coagulase-negative staphylococci or Enterococcus. BSI by Streptococcus was associated with the highest number of differentially expressed genes, indicating strong innate and adaptive immune activation. An eight-gene streptococcal classifier performed well across different Streptococcus species, and was validated in external cohorts. Plasma biomarker profiling showed that E. coli BSI was associated with the strongest response in the cytokine and systemic inflammation domain, and S. aureus BSI with the strongest endothelial cell activation. Interpretation: The causative pathogen explains a substantial part of the heterogeneity of the host response in critically ill patients with BSI. Funding: Center for Translational Molecular Medicine and the European Commission.