{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:31:24Z","timestamp":1787027484669,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009879","name":"Regione Emilia-Romagna","doi-asserted-by":"crossref","award":["E43C22000530002"],"award-info":[{"award-number":["E43C22000530002"]}],"id":[{"id":"10.13039\/501100009879","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: some consensus guidelines include C-reactive protein (CRP) in the diagnostic workup of early-onset neonatal sepsis (EOS), but its routine use remains debated due to variable diagnostic performance. The experiences and data from individual centers can help clarify its clinical utility and inform local practice. Methods: Retrospective analysis at a level III center assessing the impact of discontinuing routine C-reactive protein (CRP) testing for suspected early-onset sepsis (EOS). Laboratory use, antibiotic therapy, and outcomes in neonates of all gestational ages were compared before (2021\u20132022) and after (2024\u20132025) the policy change. Results: A total of 638 neonates were included (period 1, n = 348; period 2, n = 290). CRP testing decreased markedly (218\/348 in period 1 vs. 40\/290 in period 2; p &lt; 0.001), alongside a significant reduction in the number of complete blood counts performed (285\/348 vs. 214\/290; p = 0.02). Concurrently, both the proportion of short antibiotic courses (\u226448 h) initiated within the first 3 days of life (98\/181 vs. 88\/133) and the median duration of antibiotic therapy (48.0 h vs. 40.0 h; p &lt; 0.001) decreased without worsening outcomes. The duration of antibiotic therapy was even shorter in infants born before 34 weeks\u2019 gestation (48.0 h vs. 37.5 h; p &lt; 0.001). Conclusions: Restricting the use of CRP in the evaluation of EOS was associated with a reduction in unnecessary antibiotic exposure. This strategy may be considered a core component of neonatal antibiotic stewardship programs.<\/jats:p>","DOI":"10.3390\/antibiotics15030308","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:11:12Z","timestamp":1773828672000},"page":"308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Restricting C-Reactive Protein Use in Early-Onset Neonatal Sepsis Reduces Unnecessary Antibiotic Exposure"],"prefix":"10.3390","volume":"15","author":[{"given":"Valeria","family":"Capone","sequence":"first","affiliation":[{"name":"Pediatric Post-Graduate School, University of Modena e Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Venturelli","sequence":"additional","affiliation":[{"name":"Pediatric Post-Graduate School, University of Modena e Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Cresta","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health, School of Pediatrics Residency, Policlinico Umberto I, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5991-8949","authenticated-orcid":false,"given":"Francesca","family":"Miselli","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Maternal and Child Health, University Hospital of Modena, 41124 Modena, Italy"},{"name":"PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Via Universit\u00e0, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Buttera","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Maternal and Child Health, University Hospital of Modena, 41124 Modena, Italy"},{"name":"PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Via Universit\u00e0, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2149-0083","authenticated-orcid":false,"given":"Licia","family":"Lugli","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Maternal and Child Health, University Hospital of Modena, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Spaggiari","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Maternal and Child Health, University Hospital of Modena, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3534-7499","authenticated-orcid":false,"given":"Alberto","family":"Berardi","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Maternal and Child Health, University Hospital of Modena, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"De Rose, D.U., Ronchetti, M.P., Martini, L., Rechichi, J., Iannetta, M., Dotta, A., and Auriti, C. (2024). Diagnosis and Management of Neonatal Bacterial Sepsis: Current Challenges and Future Perspectives. Trop. Med. Infect. Dis., 9.","DOI":"10.3390\/tropicalmed9090199"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.clp.2021.05.003","article-title":"The Term Newborn: Early-Onset Sepsis","volume":"48","author":"Puopolo","year":"2021","journal-title":"Clin. Perinatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.clp.2024.10.002","article-title":"Neonatal Early-Onset Sepsis: Epidemiology, Microbiology, and Controversies in Practice","volume":"52","author":"Flannery","year":"2025","journal-title":"Clin. Perinatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0140-6736(24)00495-1","article-title":"Neonatal bacterial sepsis","volume":"404","author":"Strunk","year":"2024","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e2243691","DOI":"10.1001\/jamanetworkopen.2022.43691","article-title":"Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia","volume":"5","author":"Giannoni","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1038\/s41467-023-38156-7","article-title":"Less is more: Antibiotics at the beginning of life","volume":"14","author":"Stocker","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.idc.2014.01.005","article-title":"Antimicrobial stewardship in the NICU","volume":"28","author":"Cantey","year":"2014","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/ni.2847","article-title":"Life at the beginning: Perturbation of the microbiota by antibiotics in early life and its role in health and disease","volume":"15","author":"Zeissig","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101217","DOI":"10.1016\/j.siny.2021.101217","article-title":"Can we back off using antibiotics in the NICU?","volume":"26","author":"Fleiss","year":"2021","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/s41577-023-00874-w","article-title":"Early-life interactions between the microbiota and immune system: Impact on immune system development and atopic disease","volume":"23","author":"Donald","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.clp.2021.03.012","article-title":"Biomarkers for the Diagnosis of Neonatal Sepsis","volume":"48","author":"Cantey","year":"2021","journal-title":"Clin. Perinatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1373\/clinchem.2012.182576","article-title":"Beyond diagnostic accuracy: The clinical utility of diagnostic tests","volume":"58","author":"Bossuyt","year":"2012","journal-title":"Clin. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"114153","DOI":"10.1016\/j.jpeds.2024.114153","article-title":"Trends in C-Reactive Protein Use in Early-onset Sepsis Evaluations and Associated Antibiotic Use","volume":"273","author":"Barboza","year":"2024","journal-title":"J. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"114248","DOI":"10.1016\/j.jpeds.2024.114248","article-title":"The Emperor Has No Clothes: C-Reactive Protein for Early-Onset Sepsis","volume":"275","author":"Cantey","year":"2024","journal-title":"J. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"357","DOI":"10.2353\/jmoldx.2006.050138","article-title":"Evaluating the near-term infant for early onset sepsis: Progress and challenges to consider with 16S rDNA polymerase chain reaction testing","volume":"8","author":"Jordan","year":"2006","journal-title":"J. Mol. Diagn."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1159\/000336629","article-title":"An update on the use of C-reactive protein in early-onset neonatal sepsis: Current insights and new tasks","volume":"102","author":"Hofer","year":"2012","journal-title":"Neonatology"},{"key":"ref_17","unstructured":"National Institute for Health and Care Excellence (2024). Neonatal Infection: Antibiotics for Prevention and Treatment, National Institute for Health and Care Excellence (NICE)."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E41","DOI":"10.1542\/peds.102.4.e41","article-title":"Serial serum C-reactive protein levels in the diagnosis of neonatal infection","volume":"102","author":"Benitz","year":"1998","journal-title":"Pediatrics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/s41390-021-01861-4","article-title":"Noninfectious influencers of early-onset sepsis biomarkers","volume":"91","author":"Tiozzo","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/S0022-3476(82)80080-2","article-title":"Serum C-reactive protein and problems of newborn infants","volume":"101","author":"Ainbender","year":"1982","journal-title":"J. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2279","DOI":"10.1055\/a-2109-4109","article-title":"Exposure to Prolonged Rupture of Membranes at Term Increases the Risk for Ventilatory Support in Uninfected Neonates","volume":"41","author":"Tramontano","year":"2024","journal-title":"Am. J. Perinatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cmi.2023.02.021","article-title":"Game changer or gimmick: Inflammatory markers to guide antibiotic treatment decisions in neonatal early-onset sepsis","volume":"30","author":"Stocker","year":"2024","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5517","DOI":"10.1007\/s00431-024-05811-0","article-title":"Management of neonates at risk of early onset sepsis: A probability-based approach and recent literature appraisal: Update of the Swiss national guideline of the Swiss Society of Neonatology and the Pediatric Infectious Disease Group Switzerland","volume":"183","author":"Stocker","year":"2024","journal-title":"Eur. J. Pediatr."},{"key":"ref_24","unstructured":"Soci\u00e9t\u00e9 Fran\u00e7aise de N\u00e9onatalogie, and Soci\u00e9t\u00e9 Fran\u00e7aise de P\u00e9diatrie (2017). Prise en Charge du Nouveau-n\u00e9 \u00e0 Risque D\u2019infection N\u00e9onatale Bact\u00e9rienne Pr\u00e9coce (\u226534 SA): Recommandation de Bonne Pratique, Haute Autorit\u00e9 de Sant\u00e9 (Label M\u00e9thodologique HAS)."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e20182894","DOI":"10.1542\/peds.2018-2894","article-title":"Management of Neonates Born at \u226535 0\/7 Weeks\u2019 Gestation With Suspected or Proven Early-Onset Bacterial Sepsis","volume":"142","author":"Puopolo","year":"2018","journal-title":"Pediatrics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e20191881","DOI":"10.1542\/peds.2019-1881","article-title":"Management of Infants at Risk for Group B Streptococcal Disease","volume":"144","author":"Puopolo","year":"2019","journal-title":"Pediatrics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1038\/s41372-021-01110-w","article-title":"Antibiotic stewardship in NICU: De-implementing routine CRP to reduce antibiotic usage in neonates at risk for early-onset sepsis","volume":"41","author":"Singh","year":"2021","journal-title":"J. Perinatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jpeds.2022.12.007","article-title":"Diagnostic Performance and Patient Outcomes With C-Reactive Protein Use in Early-Onset Sepsis Evaluations","volume":"256","author":"Dhudasia","year":"2023","journal-title":"J. Pediatr."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Boscarino, G., Migliorino, R., Carbone, G., Davino, G., Dell\u2019Orto, V.G., Perrone, S., Principi, N., and Esposito, S. (2023). Biomarkers of Neonatal Sepsis: Where We Are and Where We Are Going. Antibiotics, 12.","DOI":"10.3390\/antibiotics12081233"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.1080\/14767058.2020.1856068","article-title":"C-reactive protein in early-onset neonatal sepsis\u2014A cutoff point for CRP value as a predictor of early-onset neonatal sepsis in term and late preterm infants early after birth?","volume":"35","author":"Yochpaz","year":"2022","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Berardi, A., Zinani, I., Bedetti, L., Vaccina, E., Toschi, A., Toni, G., Lecis, M., Leone, F., Monari, F., and Cozzolino, M. (2022). Should we give antibiotics to neonates with mild non-progressive symptoms? A comparison of serial clinical observation and the neonatal sepsis risk calculator. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.882416"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Berardi, A., Zinani, I., Rossi, C., Spaggiari, E., D\u2019Amico, V., Toni, G., Bedetti, L., Lucaccioni, L., Iughetti, L., and Lugli, L. (2021). Antibiotic Use in Very Low Birth Weight Neonates After an Antimicrobial Stewardship Program. Antibiotics, 10.","DOI":"10.3390\/antibiotics10040411"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e20162013","DOI":"10.1542\/peds.2016-2013","article-title":"Epidemiology of Invasive Early-Onset Neonatal Sepsis, 2005 to 2014","volume":"138","author":"Schrag","year":"2016","journal-title":"Pediatrics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1542\/peds.2010-2217","article-title":"Early onset neonatal sepsis: The burden of group B Streptococcal and E. coli disease continues","volume":"127","author":"Stoll","year":"2011","journal-title":"Pediatrics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.3109\/14767058.2015.1114093","article-title":"The burden of early-onset sepsis in Emilia-Romagna (Italy): A 4-year, population-based study","volume":"29","author":"Berardi","year":"2016","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"F248","DOI":"10.1136\/archdischild-2014-306349","article-title":"NICE neonatal early onset sepsis guidance: Greater consistency, but more investigations, and greater length of stay","volume":"100","author":"Mukherjee","year":"2015","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_37","unstructured":"National Institute for Health and Care Excellence (2017). Surveillance Report 2017\u2014Neonatal Infection Early Onset (2012) NICE Guideline CG149, National Institute for Health and Care Excellence (NICE)."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1080\/14767058.2018.1506760","article-title":"Changes of intestinal microbiota in early life","volume":"33","author":"Ficara","year":"2020","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/S1473-3099(16)30205-5","article-title":"Reducing unnecessary antibiotic use in the neonatal intensive care unit (SCOUT): A prospective interrupted time-series study","volume":"16","author":"Cantey","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zini, T., Miselli, F., D\u2019Esposito, C., Fidanza, L., Cuoghi Costantini, R., Corso, L., Mazzotti, S., Rossi, C., Spaggiari, E., and Rossi, K. (2024). Sustaining the Continued Effectiveness of an Antimicrobial Stewardship Program in Preterm Infants. Trop. Med. Infect. Dis., 9.","DOI":"10.3390\/tropicalmed9030059"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.3109\/14767058.2014.946499","article-title":"Safety of physical examination alone for managing well-appearing neonates \u226535 weeks\u2019 gestation at risk for early-onset sepsis","volume":"28","author":"Berardi","year":"2015","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1053\/siny.2001.0045","article-title":"Neonatal bacterial meningitis","volume":"6","author":"Polin","year":"2001","journal-title":"Semin. Neonatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1038\/s41390-024-03532-6","article-title":"Antibiotic exposure for culture-negative early-onset sepsis in late-preterm and term newborns: An international study","volume":"97","author":"Dimopoulou","year":"2025","journal-title":"Pediatr. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jpeds.2022.01.006","article-title":"A Proposed Framework for the Clinical Management of Neonatal \u201cCulture-Negative\u201d Sepsis","volume":"244","author":"Cantey","year":"2022","journal-title":"J. Pediatr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jpeds.2018.05.048","article-title":"Neonatal Sepsis of Early Onset, and Hospital-Acquired and Community-Acquired Late Onset: A Prospective Population-Based Cohort Study","volume":"201","author":"Giannoni","year":"2018","journal-title":"J. Pediatr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.siny.2017.03.002","article-title":"Pneumonia","volume":"22","author":"Hooven","year":"2017","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0031-3955(16)34975-6","article-title":"Necrotizing enterocolitis: Treatment based on staging criteria","volume":"33","author":"Walsh","year":"1986","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"151329","DOI":"10.1016\/j.semperi.2020.151329","article-title":"Metrics of neonatal antibiotic use","volume":"44","author":"Flannery","year":"2020","journal-title":"Semin. Perinatol."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/3\/308\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T05:22:12Z","timestamp":1773984132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/3\/308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":49,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["antibiotics15030308"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15030308","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]}}}