{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T18:18:51Z","timestamp":1774549131431,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"foundation of medical research of the OLVG"},{"name":"Amsterdam Reproduction &amp; Development research institute"},{"name":"Stichting Zeldzame Ziektefonds (ZZF)"},{"name":"De For Wis(h)dom Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Delay in the time-to-positivity of a peripheral blood culture (PBC), the gold standard for early onset neonatal sepsis (EOS) diagnosis, has resulted in excessive use of antibiotics. In this study, we evaluate the potential of the rapid Molecular Culture (MC) assay for quick EOS diagnosis. In the first part of this study, known positive and spiked blood samples were used to assess the performance of MC. In the in vivo clinical study, the second part of this study, all infants receiving antibiotics for suspicion of EOS were included. At initial EOS suspicion, a blood sample was collected for PBC and MC. MC was able to detect bacteria present in the spiked samples even when the bacterial load was low. In the clinical study, MC was positive in one infant with clinical EOS (Enterococcus faecalis) that was not detected by PBC. Additionally, MC was positive in two infants without clinical sepsis (Streptococcus mitis and multiple species), referred to as contamination. The other 37 samples were negative both by MC and PBC. MC seems to be able to detect bacteria even when the bacterial load is low. The majority of MC and PBC results were comparable and the risk for contamination and false positive MC results seems to be limited. Since MC can generate results within 4 h following sampling compared with 36\u201372 h in PBC, MC may have the potential to replace conventional PBC in EOS diagnostics in order to guide clinicians on when to discontinue antibiotic therapy several hours after birth.<\/jats:p>","DOI":"10.3390\/microorganisms11040960","type":"journal-article","created":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T04:08:03Z","timestamp":1680840483000},"page":"960","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Potential of Molecular Culture in Early Onset Neonatal Sepsis Diagnosis: A Proof of Principle Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0790-0987","authenticated-orcid":false,"given":"Thomas","family":"Dierikx","sequence":"first","affiliation":[{"name":"Department of Pediatric Gastroenterology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Neonatology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction & Development, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5128-5411","authenticated-orcid":false,"given":"Andries","family":"Budding","sequence":"additional","affiliation":[{"name":"Inbiome, 1098 XG Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martine","family":"Bos","sequence":"additional","affiliation":[{"name":"Inbiome, 1098 XG Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henri\u00ebtte","family":"van Laerhoven","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neonatology, OLVG, 1061 AE Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"van der Schoor","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neonatology, OLVG, 1061 AE Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0844-7208","authenticated-orcid":false,"given":"Hendrik","family":"Niemarkt","sequence":"additional","affiliation":[{"name":"Department of Neonatology, M\u00e1xima Medisch Centrum, 5504 DB Veldhoven, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Benninga","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"van Kaam","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction & Development, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douwe","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction & Development, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"de Meij","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.pcl.2012.12.003","article-title":"Neonatal Infectious Diseases: Evaluation of neonatal sepsis","volume":"60","author":"Spearman","year":"2013","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1016\/S0140-6736(17)31002-4","article-title":"Neonatal sepsis","volume":"390","author":"Shane","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/tropej\/fmu079","article-title":"Challenges in the diagnosis and management of neonatal sepsis","volume":"61","author":"Ochoa","year":"2015","journal-title":"J. Trop. Pediatr."},{"key":"ref_4","unstructured":"National Institute for Health and Clinical Excellence (2020, December 10). Neonatal Infection (Early Onset): Antibiotics for Prevention and Treatment (NICE Guideline 149). Available online: https:\/\/www.nice.org.uk\/guidance\/CG149."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s00431-018-3113-2","article-title":"Sepsis calculator implementation reduces empiric antibiotics for suspected early-onset sepsis","volume":"177","author":"Achten","year":"2018","journal-title":"Eur. J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3715","DOI":"10.1007\/s00431-022-04579-5","article-title":"Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: A multicenter cohort study","volume":"181","author":"Dierikx","year":"2022","journal-title":"Eur. J. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S1473-3099(14)70919-3","article-title":"Incidence of invasive group B streptococcal disease and pathogen genotype distribution in newborn babies in the Netherlands over 25 years: A nationwide surveillance study","volume":"14","author":"Bekker","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1159\/000226604","article-title":"Long-Term Trends in the Epidemiology of Neonatal Sepsis and Antibiotic Susceptibility of Causative Agents","volume":"97","author":"Gerards","year":"2010","journal-title":"Neonatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S2213-2600(18)30063-8","article-title":"The global burden of paediatric and neonatal sepsis: A systematic review","volume":"6","author":"Goldfarb","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/MOP.0000000000000338","article-title":"Adverse consequences of neonatal antibiotic exposure","volume":"28","author":"Cotten","year":"2016","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_11","first-page":"CD011926","article-title":"Molecular assays for the diagnosis of sepsis in neonates","volume":"2017","author":"Pammi","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1128\/CMR.17.4.840-862.2004","article-title":"Impact of 16S rRNA Gene Sequence Analysis for Identification of Bacteria on Clinical Microbiology and Infectious Diseases","volume":"17","author":"Clarridge","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4556","DOI":"10.1096\/fj.10-156190","article-title":"IS-pro: High-throughput molecular fingerprinting of the intestinal microbiota","volume":"24","author":"Budding","year":"2010","journal-title":"FASEB J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1128\/JCM.02886-15","article-title":"Automated Broad-Range Molecular Detection of Bacteria in Clinical Samples","volume":"54","author":"Budding","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3389\/fped.2018.00285","article-title":"Culture-Negative Early-Onset Neonatal Sepsis\u2014At the Crossroad Between Efficient Sepsis Care and Antimicrobial Stewardship","volume":"6","author":"Klingenberg","year":"2018","journal-title":"Front. Pediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1007\/s10096-019-03616-w","article-title":"Moderate positive predictive value of a multiplex real-time PCR on whole blood for pathogen detection in critically ill patients with sepsis","volume":"38","author":"Bos","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Loonen, A.J.M., Bos, M.P., Van Meerbergen, B., Neerken, S., Catsburg, A., Dobbelaer, I., Penterman, R., Maertens, G., Van De Wiel, P., and Savelkoul, P. (2013). Comparison of Pathogen DNA Isolation Methods from Large Volumes of Whole Blood to Improve Molecular Diagnosis of Bloodstream Infections. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072349"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1080\/14767058.2019.1670800","article-title":"Iatrogenic blood loss in extreme preterm infants due to frequent laboratory tests and procedures","volume":"34","author":"Counsilman","year":"2019","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"794710","DOI":"10.3389\/fped.2021.794710","article-title":"Eliminating Contamination in Umbilical Cord Blood Culture Sampling for Early-Onset Neonatal Sepsis","volume":"9","author":"Lowery","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1556\/EuJMI.4.2014.1.1","article-title":"Molecular diagnosis of sepsis: New aspects and recent developments","volume":"4","author":"Liesenfeld","year":"2014","journal-title":"Eur. J. Microbiol. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.fm.2011.02.008","article-title":"Recent advances in quantitative PCR (qPCR) applications in food microbiology","volume":"28","author":"Postollec","year":"2011","journal-title":"Food Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1590\/S0036-46652014000100012","article-title":"Enterococcus faecium AND Enterococcus faecalis in blood of newborns with suspected nosocomial infection","volume":"56","author":"Furtado","year":"2014","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Oeser, C., Pond, M., Butcher, P., Russell, A.B., Henneke, P., Laing, K., Planche, T., Heath, P.T., and Harris, K. (2020). PCR for the detection of pathogens in neonatal early onset sepsis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0226817"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1542\/peds.2006-0440","article-title":"How Reliable Is a Negative Blood Culture Result? Volume of Blood Submitted for Culture in Routine Practice in a Children\u2019s Hospital","volume":"119","author":"Connell","year":"2007","journal-title":"Pediatrics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1136\/bmj.332.7549.1089","article-title":"Comparative accuracy: Assessing new tests against existing diagnostic pathways","volume":"332","author":"Bossuyt","year":"2006","journal-title":"BMJ"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1128\/CMR.00031-13","article-title":"Early-Onset Neonatal Sepsis","volume":"27","author":"Simonsen","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"170","DOI":"10.4161\/viru.26906","article-title":"Neonatal sepsis: An old problem with new insights","volume":"5","author":"Shah","year":"2013","journal-title":"Virulence"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e526","DOI":"10.1542\/neo.9-11-e526","article-title":"Treatment and Prevention of Neonatal Anemia","volume":"9","author":"Widness","year":"2008","journal-title":"Neoreviews"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41390-021-01792-0","article-title":"Umbilical cord blood culture in neonatal early-onset sepsis: A systematic review and meta-analysis","volume":"92","author":"Dierikx","year":"2021","journal-title":"Pediatr. Res."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/4\/960\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:11:44Z","timestamp":1760123504000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/4\/960"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,7]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["microorganisms11040960"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms11040960","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,7]]}}}