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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Clinical Microbiology
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1504262
This article is part of the Research Topic Application and Reliability Assessment of Next Generation Sequencing (NGS) and targeted NGS (tNGS) in the Diagnosis of Infectious Diseases-Volume III View all 37 articles

Retrospective analysis of 300 microbial cell-free DNA sequencing results in routine blood stream infection diagnostics

Provisionally accepted
Claudio Neidhöfer Claudio Neidhöfer 1,2*Niklas Klein Niklas Klein 3Aylin Yürüktümen Aylin Yürüktümen 4Tessa Hattenhauer Tessa Hattenhauer 5Rebekka Mispelbaum Rebekka Mispelbaum 5Christian Bode Christian Bode 6Tobias Holderried Tobias Holderried 5Achim Hörauf Achim Hörauf 2Marijo Parčina Marijo Parčina 2
  • 1 Institute for Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Bonn, North Rhine-Westphalia, Germany
  • 2 Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, North Rhine-Westphalia, Germany
  • 3 Bundeswehr Central Hospital in Koblenz, Koblenz, Rhineland-Palatinate, Germany
  • 4 Department of Internal Medicine II, University Hospital Bonn, Bonn, North Rhine-Westphalia, Germany
  • 5 Department of Oncology and Hematology, Center of Integrated Oncology, University Hospital Bonn, Bonn, North Rhine-Westphalia, Germany
  • 6 Department of Anaesthesiology and Operative Intensive Care Medicine, University Hospital Bonn, Bonn, North Rhine-Westphalia, Germany

The final, formatted version of the article will be published soon.

    Bloodstream infections are a critical challenge worldwide due to the slow turnaround time of conventional microbiological tests for detecting bacteremia in septic patients. Noscendo GmbH (Duisburg, Germany) has developed the CE/IVD pipeline DISQVER for clinical metagenomics testing based on cell-free DNA (cfDNA) from blood samples to address this issue. We conducted a retrospective study to evaluate the diagnostic utility of this methodological setup in improving treatment decisions since it was introduced into our clinical setting.Between January 2021 and June 2022, the first 300 cases in which DISQVER was applied at our university hospital were collected and analyzed. The results were compared with routine microbiology test results, clinical picture, associated treatment decisions, and clinical course.Our findings demonstrate that DISQVER results where no pathogen was reported effectively ruled out bacterial bloodstream infections, whereas positive results varied in their usefulness.While the metagenomic approach proved highly valuable for detecting non-culturable and rare pathogens, its utility was limited in cases where detected microorganisms were commonly associated with the microbiota.Performing on-site analysis might mitigate delays resulting from logistical challenges and might help optimizing antibiotic stewardship. Once prompt results can be obtained, the relevance of incorporating molecular resistograms will become more pronounced. Further, the specific patient subgroups that most benefit from this analysis must be worked out. Guiding clinicians in identifying the infection focus based on the detected bacteria would significantly improve patient care. Lastly, evidence of filamentous fungi must be diligently followed up.

    Keywords: Sepsis, Bacteremia, Blood culture, Molecular Diagnostic Techniques, next generation sequencing, clinical metagenomics, cfDNA, Microbial cfDNA

    Received: 30 Sep 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Neidhöfer, Klein, Yürüktümen, Hattenhauer, Mispelbaum, Bode, Holderried, Hörauf and Parčina. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Claudio Neidhöfer, Institute for Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Bonn, 53127, North Rhine-Westphalia, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.