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Improved pathogen identification in sepsis or septic shock by clinical metagenomic sequencing

Objectives - Despite limited sensitivity and specificity, blood cultures (BCs) still represent the gold standard of diagnostic care in septic patients. We aimed to overcome current diagnostic limitations by unbiased next-generation sequencing (NGS) of circulating microbial cell-free DNA (mcfDNA) in...

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Hauptverfasser: Brenner, Thorsten (VerfasserIn) , Decker, Sebastian (VerfasserIn) , Vainshtein, Yevhen (VerfasserIn) , Grumaz, Silke (VerfasserIn) , Manoochehri, Mehdi (VerfasserIn) , Feißt, Manuel (VerfasserIn) , Seidel-Glätzer, Andrea (VerfasserIn) , Pletz, Mathias W. (VerfasserIn) , Bracht, Hendrik (VerfasserIn) , Berger, Marc M. (VerfasserIn) , Fuest, Kristina (VerfasserIn) , Blobner, Manfred (VerfasserIn) , Bach, Friedhelm (VerfasserIn) , Moerer, Onnen (VerfasserIn) , Brandenburger, Timo (VerfasserIn) , Dimski, Thomas (VerfasserIn) , Suchodolski, Klaudiusz (VerfasserIn) , Jäkel, Ulrike (VerfasserIn) , Zischkau, Jana (VerfasserIn) , Häberle, Helene (VerfasserIn) , Rosenberger, Peter (VerfasserIn) , Schürholz, Tobias (VerfasserIn) , Lindau, Simone (VerfasserIn) , Schaller, Stefan J. (VerfasserIn) , Putensen, Christian (VerfasserIn) , Dusse, Fabian (VerfasserIn) , Petros, Sirak (VerfasserIn) , Gaasch, Max (VerfasserIn) , Nußhag, Christian (VerfasserIn) , Weigand, Markus A. (VerfasserIn) , Sohn, Kai (VerfasserIn) , Glanz, Karolina (VerfasserIn) , Barth, Eberhard (VerfasserIn) , Winkler, Martin S. (VerfasserIn) , Gillmann, Hans-Jörg (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: September 2025
In: Journal of infection
Year: 2025, Jahrgang: 91, Heft: 3, Pages: 1-11
ISSN:1532-2742
DOI:10.1016/j.jinf.2025.106565
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.jinf.2025.106565
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0163445325001598
Volltext
Verfasserangaben:Thorsten Brenner, Sebastian O. Decker, Yevhen Vainshtein, Silke Grumaz, Mehdi Manoochehri, Manuel Feißt, Andrea Seidel-Glätzer, Mathias W. Pletz, Hendrik Bracht, Marc M. Berger, Kristina Fuest, Manfred Blobner, Friedhelm Bach, Onnen Moerer, Timo Brandenburger, Thomas Dimski, Klaudiusz Suchodolski, Ulrike Jäkel, Jana Zischkau, Helene Häberle, Peter Rosenberger, Tobias Schürholz, Simone Lindau, Stefan J. Schaller, Christian Putensen, Fabian Dusse, Sirak Petros, Max Gaasch, Christian Nusshag, Markus A. Weigand, Kai Sohn, Karolina Glanz, Eberhard Barth, Martin S. Winkler, Hans-Jörg Gillmann
Beschreibung
Zusammenfassung:Objectives - Despite limited sensitivity and specificity, blood cultures (BCs) still represent the gold standard of diagnostic care in septic patients. We aimed to overcome current diagnostic limitations by unbiased next-generation sequencing (NGS) of circulating microbial cell-free DNA (mcfDNA) in plasma samples. - Methods - We performed a prospective, observational, non-interventional, multicenter study (Next GeneSiS-Trial) to compare positivity rates for NGS-based identification of causative pathogens with BCs in patients suffering from sepsis or septic shock. An independent expert panel (n=3) retrospectively evaluated the plausibility of NGS-based findings and the potential for anti-infective treatment adaptations based on NGS results. - Results - The positivity rate of NGS-based diagnostics (NGS+) for 491 septic patients was 70.5% compared to positive BCs (BC+) with 19.4% within the first three days after sepsis onset. NGS+ results were evaluated as plausible in 98.6% of cases by the expert panel. Based on the experts´ recommendations, additional knowledge of NGS-based pathogen findings would have resulted in anti-infective treatment adaptations in 32.6% of all patients. Potentially inadequately treated NGS+/blood culture negative (BC-) patients showed worse outcomes. - Conclusion - The integration of NGS-based pathogen diagnostics in sepsis has the potential to improve patients´ outcomes as compared to a treatment strategy based on standard-of-care microbiological diagnostics alone.
Beschreibung:Gesehen am 11.03.2026
Beschreibung:Online Resource
ISSN:1532-2742
DOI:10.1016/j.jinf.2025.106565

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