{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T02:02:10Z","timestamp":1793671330007,"version":"4.5.1"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Background: There are wide variations in antibiotic use in neonatal intensive care units (NICUs). Limited data are available on antimicrobial stewardship (AS) programs and long-term maintenance of AS interventions in preterm very-low-birth-weight (VLBW) infants. Methods: We extended a single-centre observational study carried out in an Italian NICU. Three periods were compared: I. \u201cbaseline\u201d (2011\u20132012), II. \u201cintervention\u201d (2016\u20132017), and III. \u201cmaintenance\u201d (2020\u20132021). Intensive training of medical and nursing staff on AS occurred between periods I and II. AS protocols and algorithms were maintained and implemented between periods II and III. Results: There were 111, 119, and 100 VLBW infants in periods I, II, and III, respectively. In the \u201cintervention period\u201d, there was a reduction in antibiotic use, reported as days of antibiotic therapy per 1000 patient days (215 vs. 302, p &lt; 0.01). In the \u201cmaintenance period\u201d, the number of culture-proven sepsis increased. Nevertheless, antibiotic exposure of uninfected VLBW infants was lower, while no sepsis-related deaths occurred. Our restriction was mostly directed at shortening antibiotic regimens with a policy of 48 h rule-out sepsis (median days of early empiric antibiotics: 6 vs. 3 vs. 2 in periods I, II, and III, respectively, p &lt; 0.001). Moreover, antibiotics administered for so-called culture-negative sepsis were reduced (22% vs. 11% vs. 6%, p = 0.002), especially in infants with a birth weight between 1000 and 1499 g. Conclusions: AS is feasible in preterm VLBW infants, and antibiotic use can be safely reduced. AS interventions, namely, the shortening of antibiotic courses in uninfected infants, can be sustained over time with periodic clinical audits and daily discussion of antimicrobial therapies among staff members.<\/jats:p>","DOI":"10.3390\/tropicalmed9030059","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T08:59:37Z","timestamp":1709801977000},"page":"59","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sustaining the Continued Effectiveness of an Antimicrobial Stewardship Program in Preterm Infants"],"prefix":"10.3390","volume":"9","author":[{"given":"Tommaso","family":"Zini","sequence":"first","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, 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 Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"D\u2019Esposito","sequence":"additional","affiliation":[{"name":"Degree Program in Medicine and Surgery, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Fidanza","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9116-5198","authenticated-orcid":false,"given":"Riccardo","family":"Cuoghi Costantini","sequence":"additional","affiliation":[{"name":"PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2102-2674","authenticated-orcid":false,"given":"Lucia","family":"Corso","sequence":"additional","affiliation":[{"name":"Post-Graduate School of Paediatrics, Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8005-4261","authenticated-orcid":false,"given":"Sofia","family":"Mazzotti","sequence":"additional","affiliation":[{"name":"Post-Graduate School of Paediatrics, Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Rossi","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Spaggiari","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Rossi","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licia","family":"Lugli","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1302-4944","authenticated-orcid":false,"given":"Luca","family":"Bedetti","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41125 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 Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e20182896","DOI":"10.1542\/peds.2018-2896","article-title":"Management of Neonates Born at \u226434 6\/7 Weeks\u2019 Gestation with Suspected or Proven Early-Onset Bacterial Sepsis","volume":"142","author":"Puopolo","year":"2018","journal-title":"Pediatrics"},{"key":"ref_2","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_3","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_4","doi-asserted-by":"crossref","first-page":"4859","DOI":"10.1007\/s00431-023-05144-4","article-title":"Decreased incidence of late-onset sepsis during the SARS-CoV-2 pandemic in Italy: A multicentric study on a cohort of infants requiring major surgery","volume":"182","author":"Santisi","year":"2023","journal-title":"Eur. J. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13052-021-01028-1","article-title":"Early-onset sepsis risk calculator: A review of its effectiveness and comparative study with our evidence-based local guidelines","volume":"47","author":"Laccetta","year":"2021","journal-title":"Ital. J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"882416","DOI":"10.3389\/fped.2022.882416","article-title":"Should we give antibiotics to neonates with mild non-progressive symptoms? A comparison of serial clinical observation and the neonatal sepsis risk calculator","volume":"10","author":"Berardi","year":"2022","journal-title":"Front. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"621663","DOI":"10.3389\/fped.2020.621663","article-title":"Editorial: Sepsis in Neonates and Children","volume":"8","author":"Giannoni","year":"2020","journal-title":"Front. Pediatr."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1136\/archdischild-2022-325113","article-title":"Early initiation of antibiotic therapy and short-term outcomes in preterm infants: A single-centre retrospective cohort analysis","volume":"108","author":"Bubser","year":"2023","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2022059427","DOI":"10.1542\/peds.2022-059427","article-title":"Early Antibiotic Use and Neonatal Outcomes among Preterm Infants without Infections","volume":"151","author":"Yu","year":"2023","journal-title":"Pediatrics"},{"key":"ref_11","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_12","doi-asserted-by":"crossref","unstructured":"Minotti, C., Di Caprio, A., Facchini, L., Bedetti, L., Miselli, F., Rossi, C., Muttini, E.D.C., Lugli, L., Luppi, L., and Ferrari, F. (2023). Antimicrobial Resistance Pattern and Empirical Antibiotic Treatments in Neonatal Sepsis: A Retrospective, Single-Center, 12-Year Study. Antibiotics, 12.","DOI":"10.3390\/antibiotics12101488"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Berardi, A., Sforza, F., Baroni, L., Spada, C., Ambretti, S., Biasucci, G., Bolognesi, S., Capretti, M., Carretto, E., and Ciccia, M. (2019). Epidemiology and complications of late-onset sepsis: An Italian area-based study. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0225407"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/jac\/dkad358","article-title":"Variation in antibiotic consumption in very preterm infants-a 10 year population-based study","volume":"79","author":"Huncikova","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100727","DOI":"10.1016\/j.eclinm.2021.100727","article-title":"A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study","volume":"32","author":"Prusakov","year":"2021","journal-title":"eClinicalMedicine"},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.cmi.2017.08.026","article-title":"What is antimicrobial stewardship?","volume":"23","author":"Dyar","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_18","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_19","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."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41372-018-0041-y","article-title":"Reducing antibiotic utilization rate in preterm infants: A quality improvement initiative","volume":"38","author":"Bhat","year":"2018","journal-title":"J. Perinatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.jiac.2019.04.012","article-title":"A simple and feasible antimicrobial stewardship pro-gram in a neonatal intensive care unit of a Japanese community hospital","volume":"25","author":"Kitano","year":"2019","journal-title":"J. Infect. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1097\/INF.0000000000003462","article-title":"Antimicrobial Stewardship at Birth in Preterm Infants: Not Just About a Decrease!","volume":"41","author":"Stritzke","year":"2022","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1097\/INF.0000000000002039","article-title":"Reduction of Inappropriate Antimicrobial Prescriptions in a Tertiary Neonatal Intensive Care Unit after Antimicrobial Stewardship Care Bundle Implementation","volume":"38","author":"Ting","year":"2019","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1097\/CCM.0000000000003463","article-title":"Implementation of the Smart Use of Antibiotics Program to Reduce Unnecessary Antibiotic Use in a Neonatal ICU: A Prospective Interrupted Time-Series Study in a Developing Country","volume":"47","author":"Lu","year":"2019","journal-title":"Crit. Care Med."},{"key":"ref_25","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_26","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_27","doi-asserted-by":"crossref","first-page":"F327","DOI":"10.1136\/archdischild-2018-315412","article-title":"Challenges and opportunities for antibiotic stewardship among preterm infants","volume":"104","author":"Mukhopadhyay","year":"2019","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Miselli, F., Crestani, S., Maugeri, M., Passini, E., Spaggiari, V., Deonette, E., \u0106osi\u0107, B., Rossi, K., Roversi, M.F., and Bedetti, L. (2023). Late-Onset Sepsis Mortality among Preterm Infants: Beyond Time to First Antibiotics. Microorganisms., 11.","DOI":"10.3390\/microorganisms11020396"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13756-022-01057-3","article-title":"Neonatal ICU antibiotic use trends within an integrated delivery network","volume":"11","author":"Boverman","year":"2022","journal-title":"Antimicrob. Resist. Infect. Control."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1111\/apa.14337","article-title":"Antimicrobial stewardship in the neonatal unit reduces antibiotic exposure","volume":"107","author":"McCarthy","year":"2018","journal-title":"Acta Paediatr."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1093\/jpids\/piy043","article-title":"Antibiotic Stewardship in the Neonatal Intensive Care Unit: Effects of an Automatic 48-Hour Antibiotic Stop Order on Antibiotic Use","volume":"8","author":"Astorga","year":"2019","journal-title":"J. Pediatric Infect. Dis. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1055\/s-0036-1584522","article-title":"Implementation of an Automatic Stop Order and Initial Antibiotic Exposure in Very Low Birth Weight Infants","volume":"34","author":"Desai","year":"2017","journal-title":"Am. J. Perinatol."},{"key":"ref_34","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 An-timicrobial Stewardship","volume":"6","author":"Klingenberg","year":"2018","journal-title":"Front. Pediatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1159\/000511710","article-title":"Antibiotic Stewardship in Premature Infants: A Systematic Review","volume":"117","author":"Rajar","year":"2020","journal-title":"Neonatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e180164","DOI":"10.1001\/jamanetworkopen.2018.0164","article-title":"Temporal Trends and Center Variation in Early Antibiotic Use Among Premature Infants","volume":"1","author":"Flannery","year":"2018","journal-title":"JAMA Netw. Open"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.jhin.2009.09.010","article-title":"Routine antibiotic use in preterm neonates: A randomised controlled trial","volume":"74","author":"Tagare","year":"2010","journal-title":"J. Hosp. Infect."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/INF.0000000000003380","article-title":"Antimicrobial Susceptibility Profiles Among Neonatal Early-onset Sepsis Pathogens","volume":"41","author":"Flannery","year":"2022","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41372-020-00784-y","article-title":"Delivery-based criteria for empiric antibiotic administration among preterm infants","volume":"41","author":"Garber","year":"2021","journal-title":"J. Perinatol."}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/9\/3\/59\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:10:10Z","timestamp":1760105410000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/9\/3\/59"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,7]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["tropicalmed9030059"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed9030059","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,7]]}}}