Next Generation Sequencing of Free Microbial DNA for Rapid Identification of Pathogens in Critically Ill Children with Systemic Inflammatory Response Syndrome (SIRS)

Background: Infections, major surgeries, and hyperinflammatory syndromes are known to trigger Systemic Inflammatory Response Syndrome (SIRS). Discrimination between infectious and noninfectious inflammation often poses a challenge in chronically ill patients with multiple comorbidities. These patien...

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Main Authors: Sarah C. Goretzki, Miriam Schäfer, Burcin Dogan, Nora Bruns, Eva Tschiedel, Peter-Michael Rath, Sebastian Voigt, Silke Grumaz, Petra Horvatek, Stefan Schönberger, Florian Stehling, Thorsten Brenner, Christian Dohna-Schwake
Format: Article
Language:English
Published: IMR Press 2022-11-01
Series:Frontiers in Bioscience-Landmark
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Online Access:https://www.imrpress.com/journal/FBL/27/11/10.31083/j.fbl2711302
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author Sarah C. Goretzki
Miriam Schäfer
Burcin Dogan
Nora Bruns
Eva Tschiedel
Peter-Michael Rath
Sebastian Voigt
Silke Grumaz
Petra Horvatek
Stefan Schönberger
Florian Stehling
Thorsten Brenner
Christian Dohna-Schwake
author_facet Sarah C. Goretzki
Miriam Schäfer
Burcin Dogan
Nora Bruns
Eva Tschiedel
Peter-Michael Rath
Sebastian Voigt
Silke Grumaz
Petra Horvatek
Stefan Schönberger
Florian Stehling
Thorsten Brenner
Christian Dohna-Schwake
author_sort Sarah C. Goretzki
collection DOAJ
description Background: Infections, major surgeries, and hyperinflammatory syndromes are known to trigger Systemic Inflammatory Response Syndrome (SIRS). Discrimination between infectious and noninfectious inflammation often poses a challenge in chronically ill patients with multiple comorbidities. These patients are routinely treated with a variety of anti-infective medications before a pathogen is identified. With the goal of improving pathogen detection rates and interventions, we evaluated Next Generation Sequencing (NGS) as a highly sensitive and fast means of detecting free microbial DNA in a small amount of serum samples from children with ongoing SIRS. Methods: We describe seven complex pediatric patients of SIRS or prolonged fever (>38.5 °C) >72 hours in which serum samples analyzed by NGS had a major impact on therapy. One patient was analyzed twice. Results: In eight NGS there were six positive results (two bacterial, three viral, one fungal) which were subsequently confirmed by microbiological culture or polymerase chain reaction (PCR) in five of the six NGS. In five of the eight performed NGS, results led to a change of therapy: antibiotic therapy was discontinued in two, escalated in one, an initiated in another; in one an antiviral was administered. Conclusions: NGS may become a valuable addition to infectious disease diagnostics in cases of pediatric SIRS. However, NGS has not yet been validated as a diagnostic method in pediatric as a diagnostic method in pediatric patients and results should therefore be interpreted with caution. Multi-center NGS evaluation studies are currently being planned.
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spelling doaj.art-30bb5a0381bd42fb90108990bd23aeb62022-12-22T02:49:13ZengIMR PressFrontiers in Bioscience-Landmark2768-67012022-11-01271130210.31083/j.fbl2711302S2768-6701(22)00658-XNext Generation Sequencing of Free Microbial DNA for Rapid Identification of Pathogens in Critically Ill Children with Systemic Inflammatory Response Syndrome (SIRS)Sarah C. Goretzki0Miriam Schäfer1Burcin Dogan2Nora Bruns3Eva Tschiedel4Peter-Michael Rath5Sebastian Voigt6Silke Grumaz7Petra Horvatek8Stefan Schönberger9Florian Stehling10Thorsten Brenner11Christian Dohna-Schwake12Department of Pediatrics I, Neonatology, Pediatric Intensive Care, Pediatric Neurology, Pediatric Infectious Diseases, Essen University Hospital, 45147 Essen, GermanyDepartment of Pediatrics I, Neonatology, Pediatric Intensive Care, Pediatric Neurology, Pediatric Infectious Diseases, Essen University Hospital, 45147 Essen, GermanyDepartment of Pediatrics I, Neonatology, Pediatric Intensive Care, Pediatric Neurology, Pediatric Infectious Diseases, Essen University Hospital, 45147 Essen, GermanyDepartment of Pediatrics I, Neonatology, Pediatric Intensive Care, Pediatric Neurology, Pediatric Infectious Diseases, Essen University Hospital, 45147 Essen, GermanyDepartment of Pediatrics I, Neonatology, Pediatric Intensive Care, Pediatric Neurology, Pediatric Infectious Diseases, Essen University Hospital, 45147 Essen, GermanyInstitute of Medical Microbiology, University Medicine Essen, University Duisburg-Essen, 45147 Essen, GermanyInstitute of Virology, University Medicine Essen, University Duisburg-Essen, 45147 Essen, GermanyNoscendo GmbH, Duisburg, 47198 Duisburg, GermanyNoscendo GmbH, Duisburg, 47198 Duisburg, GermanyDepartment of Pediatrics III, Pediatric Hematology and Oncology, Cardiology, Pulmonology, University Hospital Essen, 45147 Essen, GermanyDepartment of Pediatrics III, Pediatric Hematology and Oncology, Cardiology, Pulmonology, University Hospital Essen, 45147 Essen, GermanyDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, GermanyDepartment of Pediatrics I, Neonatology, Pediatric Intensive Care, Pediatric Neurology, Pediatric Infectious Diseases, Essen University Hospital, 45147 Essen, GermanyBackground: Infections, major surgeries, and hyperinflammatory syndromes are known to trigger Systemic Inflammatory Response Syndrome (SIRS). Discrimination between infectious and noninfectious inflammation often poses a challenge in chronically ill patients with multiple comorbidities. These patients are routinely treated with a variety of anti-infective medications before a pathogen is identified. With the goal of improving pathogen detection rates and interventions, we evaluated Next Generation Sequencing (NGS) as a highly sensitive and fast means of detecting free microbial DNA in a small amount of serum samples from children with ongoing SIRS. Methods: We describe seven complex pediatric patients of SIRS or prolonged fever (>38.5 °C) >72 hours in which serum samples analyzed by NGS had a major impact on therapy. One patient was analyzed twice. Results: In eight NGS there were six positive results (two bacterial, three viral, one fungal) which were subsequently confirmed by microbiological culture or polymerase chain reaction (PCR) in five of the six NGS. In five of the eight performed NGS, results led to a change of therapy: antibiotic therapy was discontinued in two, escalated in one, an initiated in another; in one an antiviral was administered. Conclusions: NGS may become a valuable addition to infectious disease diagnostics in cases of pediatric SIRS. However, NGS has not yet been validated as a diagnostic method in pediatric as a diagnostic method in pediatric patients and results should therefore be interpreted with caution. Multi-center NGS evaluation studies are currently being planned.https://www.imrpress.com/journal/FBL/27/11/10.31083/j.fbl2711302sirschildrennext generation sequencing
spellingShingle Sarah C. Goretzki
Miriam Schäfer
Burcin Dogan
Nora Bruns
Eva Tschiedel
Peter-Michael Rath
Sebastian Voigt
Silke Grumaz
Petra Horvatek
Stefan Schönberger
Florian Stehling
Thorsten Brenner
Christian Dohna-Schwake
Next Generation Sequencing of Free Microbial DNA for Rapid Identification of Pathogens in Critically Ill Children with Systemic Inflammatory Response Syndrome (SIRS)
Frontiers in Bioscience-Landmark
sirs
children
next generation sequencing
title Next Generation Sequencing of Free Microbial DNA for Rapid Identification of Pathogens in Critically Ill Children with Systemic Inflammatory Response Syndrome (SIRS)
title_full Next Generation Sequencing of Free Microbial DNA for Rapid Identification of Pathogens in Critically Ill Children with Systemic Inflammatory Response Syndrome (SIRS)
title_fullStr Next Generation Sequencing of Free Microbial DNA for Rapid Identification of Pathogens in Critically Ill Children with Systemic Inflammatory Response Syndrome (SIRS)
title_full_unstemmed Next Generation Sequencing of Free Microbial DNA for Rapid Identification of Pathogens in Critically Ill Children with Systemic Inflammatory Response Syndrome (SIRS)
title_short Next Generation Sequencing of Free Microbial DNA for Rapid Identification of Pathogens in Critically Ill Children with Systemic Inflammatory Response Syndrome (SIRS)
title_sort next generation sequencing of free microbial dna for rapid identification of pathogens in critically ill children with systemic inflammatory response syndrome sirs
topic sirs
children
next generation sequencing
url https://www.imrpress.com/journal/FBL/27/11/10.31083/j.fbl2711302
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