Related Experiment Video
Updated: Jan 5, 2026
Using the Overlay Assay to Qualitatively Measure Bacterial Production of and Sensitivity to Pneumococcal Bacteriocins
Published on: September 30, 2014
Update of a clinical prediction model for serious bacterial infections in preschool children by adding a
Chantal van Houten1, Josephine Sophia van de Maat2, Christiana Naaktgeboren3
1Paediatric infectious diseases, University Medical Centre Utrecht, Utrecht, The Netherlands.
Insights
A new combination assay improved the Feverkidstool's accuracy in identifying serious bacterial infections (SBIs) in children. This updated model helps rule out bacterial infections, reducing unnecessary antibiotic use in low-to-moderate risk cases.
Area of Science:
- Pediatric infectious diseases
- Diagnostic test development
- Biomarker research
Background:
- Accurate diagnosis of serious bacterial infections (SBIs) in febrile children is crucial.
- Existing diagnostic models like Feverkidstool require optimization for improved accuracy.
- Novel biomarkers may enhance the ability to differentiate bacterial from viral infections.
Purpose of the Study:
- To evaluate if a novel combination assay can improve the diagnostic accuracy of the Feverkidstool for identifying pneumonia and other SBIs in children.
- To assess the performance of an updated Feverkidstool model incorporating a new biomarker panel.
Main Methods:
- An observational, double-blind diagnostic study was conducted across six hospitals in Israel and the Netherlands.
- 591 children (1-60 months) with respiratory infections or fever were enrolled.
- The Feverkidstool model was recalibrated and updated by replacing C-reactive protein (CRP) with a combination assay (tumor necrosis factor-related apoptosis-inducing ligand, interferon-gamma induced protein-10, and CRP).
Main Results:
- The original Feverkidstool showed good discrimination for SBIs (c-statistic for pneumonia: 0.84, other SBIs: 0.82).
- Replacing CRP with the combination assay significantly improved diagnostic ability (c-statistic for pneumonia: 0.89, other SBIs: 0.91).
- The updated model particularly enhanced SBIs diagnosis in children with low-to-moderate risk estimates.
Conclusions:
- The updated Feverkidstool, utilizing a combination assay, demonstrates improved diagnostic accuracy for pneumonia and other SBIs in febrile children.
- This enhanced model shows significant potential for ruling out bacterial infections, thereby reducing unnecessary antibiotic prescriptions in children with lower predicted risk.
Objective:
To determine whether updating a diagnostic prediction model by adding a combination assay (tumour necrosis factor-related apoptosis-inducing ligand, interferon γ induced protein-10 and C reactive protein (CRP)) can accurately identify children with pneumonia or other serious bacterial infections (SBIs).
Design:
Observational double-blind diagnostic study.
Setting:
Two hospitals in Israel and four hospitals in the Netherlands.
Patients:
591 children, aged 1-60 months, presenting with lower respiratory tract infections or fever without source. 96 of them had SBIs. The original Feverkidstool, a polytomous logistic regression model including clinical variables and CRP, was recalibrated and thereafter updated by using the assay.
Main Outcome Measures:
Pneumonia, other SBIs or no SBI.
Results:
The recalibrated original Feverkidstool discriminated well between SBIs and viral infections, with a c-statistic for pneumonia of 0.84 (95% CI 0.77 to 0.92) and 0.82 (95% CI 0.77 to 0.86) for other SBIs. The discriminatory ability increased when CRP was replaced by the combination assay; c-statistic for pneumonia increased to 0.89 (95% CI 0.82 to 0.96) and for other SBIs to 0.91 (95% CI 0.87 to 0.94). This updated Feverkidstool improved diagnosis of SBIs mainly in children with low-moderate risk estimates of SBIs.
Conclusion:
We improved the diagnostic accuracy of the Feverkidstool by replacing CRP with a combination assay to predict pneumonia or other SBIs in febrile children. The updated Feverkidstool has the largest potential to rule out bacterial infections and thus to decrease unnecessary antibiotic prescription in children with low-to-moderate predicted risk of SBIs.
