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Updated: Nov 1, 2025
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Next-generation sequencing diagnostics of bacteremia in pediatric sepsis
Thomas Schmoch1,2, Jens H Westhoff3, Sebastian O Decker2
1Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen.
Insights
Next-generation sequencing (NGS) offers a faster, more sensitive method for diagnosing sepsis in children compared to traditional blood cultures. This study evaluates NGS
Area of Science:
- Pediatric critical care medicine
- Infectious diseases
- Molecular diagnostics
Background:
- Sepsis and septic shock disproportionately affect neonates and young children, necessitating rapid and accurate diagnosis.
- Current culture-based diagnostics are often insensitive in pediatric patients and have long turnaround times.
- Next-generation sequencing (NGS) of cell-free DNA shows promise for pathogen identification in adult sepsis but requires validation in pediatric populations.
Purpose of the Study:
- To evaluate the diagnostic performance of an NGS-based approach for identifying pathogens in pediatric patients with sepsis.
- To compare the efficacy of NGS with standard culture-based diagnostic methods.
- To assess the potential impact of NGS results on anti-infective treatment regimens in critically ill children.
Main Methods:
- A prospective, observational, multicenter study (Next GeneSiPS-Trial) involving neonates, infants, and toddlers with suspected or proven sepsis.
- Utilizing an NGS-based approach for pathogen identification from plasma samples.
- Comparing NGS results against standard culture-based microbiological diagnostics and retrospectively analyzing treatment changes.
Main Results:
- The study aims to determine the sensitivity and specificity of NGS in identifying causative pathogens in pediatric sepsis.
- It will quantify the diagnostic performance using the sepsis indicating quantifier (SIQ) score.
- The potential for NGS to guide or alter anti-infective therapy will be assessed.
Conclusions:
- There is an urgent need for faster and more sensitive diagnostic tools for pediatric sepsis.
- This study will provide crucial data on the utility of NGS in critically ill children with sepsis.
- The findings may lead to improved diagnostic and treatment strategies for pediatric sepsis.
Introduction:
Sepsis and septic shock are the most severe forms of infection affecting predominantly elderly people, preterm and term neonates, and young infants. Even in high-income countries sepsis causes about 8% of admissions to pediatric intensive care units (PICUs). Early diagnosis, rapid anti-infective treatment, and prompt hemodynamic stabilization are crucial for patient survival. In this context, it is essential to identify the causative pathogen as soon as possible to optimize antimicrobial treatment. To date, culture-based diagnostic procedures (e.g., blood cultures) represent the standard of care. However, they have 2 major problems: on the one hand, in the case of very small sample volumes (and thus usually in children), they are not sufficiently sensitive. On the other hand, with a time-to-result of 2 to 5 days, blood cultures need a relatively long time for the anti-infective therapy to be calculated. To overcome these problems, culture-independent molecular diagnostic procedures such as unbiased sequence analysis of circulating cell-free DNA (cfDNA) from plasma samples of septic patients by next-generation sequencing (NGS) have been tested successfully in adult septic patients. However, these results still need to be transferred to the pediatric setting.
Methods:
The Next GeneSiPS-Trial is a prospective, observational, non-interventional, multicenter study used to assess the diagnostic performance of an NGS-based approach for the identification of causative pathogens in (preterm and term) neonates (d1-d28, n = 50), infants (d29 to <1 yr, n = 50), and toddlers (1 yr to <5 yr, n = 50) with suspected or proven severe sepsis or septic shock (according to the pediatric sepsis definition) by the use of the quantitative sepsis indicating quantifier (SIQ) score in comparison to standard of care (culture-based) microbiological diagnostics. Potential changes in anti-infective treatment regimens based on these NGS results will be estimated retrospectively by a panel of 3 independent clinical specialists.
Discussion:
Neonates, infants, and young children are significantly affected by sepsis. Fast and more sensitive diagnostic approaches are urgently needed. This prospective, observational, non-interventional, multicenter study seeks to evaluate an NGS-based approach in critically ill children suffering from sepsis.
Trial Registration:
DRKS-ID: DRKS00015705 (registered October 24, 2018). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015705.
