Abstract

Sepsis, defined as life-threatening organ dysfunction caused by infection is difficult to distinguish clinically from infection or post-operative inflammation. We hypothesized that in a heterogeneous group of critically ill children, there would be different metabolic profiles between post-operative inflammation, bacterial and viral infection and infection with or without organ dysfunction. 1D 1H nuclear magnetic resonance spectra were acquired in plasma samples from critically ill children. We included children with bacterial (n = 25) and viral infection (n = 30) and controls (n = 58) (elective cardiac surgery without infection). Principal component analysis was used for data exploration and partial least squares discriminant analysis models for the differences between groups. Area under receiver operating characteristic curve (AUC) values were used to evaluate the models. Univariate analysis demonstrated differences between controls and bacterial and viral infection. There was excellent discrimination between bacterial and control (AUC = 0.94), and viral and control (AUC = 0.83), with slightly more modest discrimination between bacterial and viral (AUC = 0.78). There was modest discrimination (AUC = 0.73) between sepsis with organ dysfunction and infection with no organ dysfunction. In critically ill children, NMR metabolomics differentiates well between those with a post-operative inflammation but no infection, and those with infection (bacterial and viral), and between sepsis and infection.

Highlights

  • Sepsis, defined as life-threatening organ dysfunction caused by infection is difficult to distinguish clinically from infection or post-operative inflammation

  • Consecutive children admitted to a large tertiary centre paediatric intensive care unit (PICU), were recruited and categorised into those with bacterial or viral infection and controls

  • Consecutive admissions were selected if there was sufficient plasma for metabolomic analysis, and if there was a clean phenotype of defined criteria

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Summary

Introduction

Sepsis, defined as life-threatening organ dysfunction caused by infection is difficult to distinguish clinically from infection or post-operative inflammation. We hypothesized that in a heterogeneous group of critically ill children, there would be different metabolic profiles between post-operative inflammation, bacterial and viral infection and infection with or without organ dysfunction. Ascertainment of bacterial aetiology is based on detection by culture, PCR or antigen in a sterile site, such as blood, cerebrospinal fluid, urine or intra-operative specimens. Viral aetiology is ascertained by viral PCR of respiratory specimens, blood, urine, CSF or other sterile site fluid. These microbiological investigations is may be augmented by laboratory tests (biochemical and haematological) and imaging studies such as chest X-ray, CT or MRI scan. Klebsiella pneumoniae (2) Methicillin Resistant Staphylococcus aureus (1) Neisseria meningitidis (11) Pseudomonas aeruginosa (2) Stenotrophomonas maltophilia (1) Streptococcus pneumoniae (4) Streptococcus pyogenes (4)

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