Parkinson, Edward C;
Watkins, W John;
Edkins, Sarah;
McLaren, James E;
Clements, Michelle N;
Andrews, Robert;
Liberatore, Federico;
... NeoVanc Consortium; + view all
(2025)
A rapid time-resolved host gene expression signature predicts responses to antibiotic treatment in neonatal bacterial sepsis.
Science Translational Medicine
, 17
(826)
10.1126/scitranslmed.adt1938.
Preview |
Text
Clements_ExtractPage1.pdf Download (1MB) | Preview |
Abstract
Sepsis is a leading cause of mortality and morbidity in neonates yet remains difficult to diagnose. This leads to widespread empiric antibiotic therapy, which can facilitate the development of antimicrobial resistance. How the dysregulated host response to infection and sepsis evolves after antibiotic treatment is poorly understood. Temporal gene expression in neonates with microbiologically confirmed sepsis, treated with the antibiotic vancomycin as part of a randomized controlled trial, was profiled to reveal a treatment-responsive gene signature. The signature exhibited a rapid reversal of the septic state, observable within 24 hours of the initiation of therapy. Unexpectedly, response rates associated with the adaptive immune system were among the fastest, and these changes were reproduced in both pediatric and adult patients with sepsis, indicating conservation and reversibility of sepsis signatures across the life course. We demonstrated how these treatment-responsive genes could be translated into a prognostic clinical measure, exhibiting strong agreement with clinical assessments. Network modeling of sepsis-responsive genes identified a signature associated with treatment comprising an early transient elevation of antimicrobial defensive genes, suggesting an impaired bactericidal response in neonatal sepsis. These findings suggest that the host response is regulated in sepsis and offer insights into early prognostic approaches for reducing antibiotic overuse.
| Type: | Article |
|---|---|
| Title: | A rapid time-resolved host gene expression signature predicts responses to antibiotic treatment in neonatal bacterial sepsis |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1126/scitranslmed.adt1938 |
| Publisher version: | https://doi.org/10.1126/scitranslmed.adt1938 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Humans, Anti-Bacterial Agents, Infant, Newborn, Neonatal Sepsis, Gene Expression Profiling, Vancomycin, Adult, Male, Sepsis, Time Factors, Female, Transcriptome |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10218859 |
Archive Staff Only
 |
View Item |
