{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T20:26:14Z","timestamp":1788639974296,"version":"build-2803163510"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017590","name":"Universit\u00e4tsklinikum Essen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017590","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cell Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rapid and accurate pathogen detection is critical for optimizing outcomes in pediatric sepsis. Next-generation sequencing (NGS) of cell-free DNA (cfDNA) from blood enables culture-independent identification of microbial DNA from bacteria, viruses, fungi, and parasites. We evaluated the diagnostic yield and clinical impact of cfDNA-based NGS in critically ill and predominantly immunocompromised pediatric patients (\u2264\u200918 years) with suspected infection.<\/jats:p>\n                    <jats:p>This retrospective single-center study included pediatric patients who underwent plasma cfDNA-NGS at a tertiary care hospital in Germany. Following computational removal of human DNA, remaining sequences were aligned to curated microbial reference databases. Diagnostic performance was compared with blood cultures and viral PCR, and clinical relevance was assessed by pediatric infectious disease specialists.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>111 tests in 78 pediatric patients, mostly with systemic inflammatory response syndrome of unknown etiology, were performed. Overall, 61 tests (54.5%) were positive for pathogenic cfDNA. Compared with conventional microbiological diagnostics, NGS demonstrated a sensitivity of 64.7% and specificity of 88.2% when blood cultures and viral PCR served as the reference standard. NGS identified additional pathogens in a substantial proportion (41.1%) of cases that remained negative by standard testing. Of those pathogens only found by NGS, over 60% were deemed clinically relevant. In 14.8% of positive NGS results, a pathogen-specific therapy was started, while 40.2% of tests led to a discontinuation of therapy (51.0% of negative tests). Out of all positive NGS, 38 (62.3%) were classified as clinically relevant. NGS testing also detected rare infections with fungi and parasites in four cases each.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Detection of pathogenic cfDNA through NGS from blood shows promising results as an additional diagnostic tool in critically ill pediatric patients with suspected infections. Clinical utility is currently still limited by its high cost, undetermined diagnostic validity and limitations in testing for resistances and restricted availability of raw sequencing data due to data-protection constraints.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40348-026-00226-3","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T11:50:30Z","timestamp":1775649030000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Next-generation sequencing of cell-free microbial DNA in blood samples of critically ill children: a single-center experience"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4446-8257","authenticated-orcid":false,"given":"Jonas E.","family":"Adolph","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Pentek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bauch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Held","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4570-877X","authenticated-orcid":false,"given":"Thorsten","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7765-8893","authenticated-orcid":false,"given":"Ursula","family":"Felderhoff-M\u00fcser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7912-7806","authenticated-orcid":false,"given":"Silke","family":"Grumaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Horvatek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2724-5297","authenticated-orcid":false,"given":"Mathis","family":"Steindor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Asar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1544-9903","authenticated-orcid":false,"given":"Sebastian","family":"Voigt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Dziobaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-5406","authenticated-orcid":false,"given":"Christian","family":"Dohna-Schwake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5218-070X","authenticated-orcid":false,"given":"Sarah C.","family":"Goretzki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"226_CR1","doi-asserted-by":"publisher","first-page":"2409","DOI":"10.1097\/CCM.0000000000000509","volume":"42","author":"SL Weiss","year":"2014","unstructured":"Weiss SL, Fitzgerald JC, Balamuth F, Alpern ER, Lavelle J, Chilutti M et al (2014) Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. 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The requirement for written informed consent was waived due to the retrospective design and anonymised data analysis. All procedures followed the ethical standards of the institutional research committee and the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable. The manuscript does not contain any individual person\u2019s identifiable data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Silke Grumaz is a co-founder, employee and shareholder of Noscendo GmbH.Petra Horvatek is a former employee of Noscendo GmbH.Thorsten Brenner has received a lecture honorarium from Noscendo GmbH.All other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12"}}