{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:01:26Z","timestamp":1790636486241,"version":"4.1.0"},"reference-count":86,"publisher":"Georg Thieme Verlag KG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Late-onset neonatal sepsis (LOS) remains a major challenge in modern neonatal intensive care units (NICUs), disproportionately affecting very low birth weight (VLBW) and extremely preterm infants. Despite advances in perinatal care, LOS continues to contribute to high mortality, prolonged hospitalization, and long-term neurodevelopmental impairment. Emerging trends\u2014including evolving pathogen profiles, increased antimicrobial resistance (AMR), and widespread microbiome disruption\u2014highlight persistent clinical and public health concerns. This review synthesizes current evidence on the epidemiology, pathophysiology, diagnosis, and management of LOS, with emphasis on evolving diagnostics, antimicrobial stewardship, prevention strategies, and emerging precision approaches. Key gaps and research priorities are highlighted to inform future clinical practice and neonatal health policy.<\/jats:p>\n                  <jats:p>This narrative review synthesizes contemporary literature, including multicenter cohort studies, national registries, and emerging diagnostic and predictive technologies.<\/jats:p>\n                  <jats:p>LOS arises from the complex interplay between neonatal immune immaturity, invasive NICU interventions, and microbial exposure. Gram-positive organisms predominate in high-income settings, whereas multidrug-resistant Gram-negative pathogens are increasingly reported in low- and middle-income countries, contributing to higher morbidity and mortality. Early-life antibiotic exposure and dysbiosis compromise the gut microbiome, further increasing susceptibility. Clinical recognition remains challenging due to nonspecific signs, often leading to delayed or excessive empiric antibiotic therapy. Rapid molecular diagnostics, emerging predictive tools, including early-warning models, and serial biomarker monitoring offer opportunities for pathogen-directed therapy, individualized pharmacokinetic optimization, and safe antimicrobial stewardship. Prevention through central-line bundles, human milk feeding, probiotics, strict hand hygiene, and context-specific infection-control strategies remains central to reducing LOS incidence.<\/jats:p>\n                  <jats:p>LOS represents a multifactorial syndrome with profound implications for survival and neurodevelopment in preterm and VLBW infants. Effective management requires integration of precision diagnostics, individualized therapy, microbiome-preserving strategies, neuroprotective interventions, and equitable implementation of prevention and stewardship programs. Bridging mechanistic understanding with scalable, context-sensitive approaches is critical to improving survival, reducing morbidity, and optimizing long-term outcomes.<\/jats:p>","DOI":"10.1055\/a-2938-3600","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T23:14:43Z","timestamp":1786749283000},"source":"Crossref","is-referenced-by-count":0,"title":["Late-Onset Neonatal Sepsis: Contemporary Epidemiology, Diagnosis, Prevention, and Precision Therapeutics"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1133-6956","authenticated-orcid":false,"given":"Shweta","family":"Dixit","sequence":"additional","affiliation":[{"name":"MetroHealth Hospital, Ohio, United States","place":["Cleveland"],"department":["Department of Neonatology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Dixit","sequence":"additional","affiliation":[{"name":"Saint Louis University College for Public Health and Social Justice, Missouri, United States","place":["St. Louis"],"department":["Department of Epidemiology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashwant Kumar","family":"Rao","sequence":"additional","affiliation":[{"name":"Ganesh Shankar Vidyarthi Memorial Medical College, Uttar Pradesh, India","place":["Kanpur"],"department":["Department of Pediatrics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4078-049X","authenticated-orcid":false,"given":"Anirudha","family":"Das","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Children's Hospital, Ohio, United States","place":["Cleveland"],"department":["Department of Neonatology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"05","key":"ref1","doi-asserted-by":"crossref","first-page":"e2023062223","DOI":"10.1542\/peds.2023-062223","article-title":"Late-onset sepsis in very low birth weight infants","volume":"152","author":"G Klinger","year":"2023","journal-title":"Pediatrics"},{"issue":"06","key":"ref2","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1159\/000539245","article-title":"Late-onset sepsis among extremely preterm\ninfants of 24\u201328 weeks gestation: an international comparison in 10 high-income countries","volume":"121","author":"G Klinger","year":"2024","journal-title":"Neonatology"},{"issue":"02","key":"ref3","doi-asserted-by":"crossref","first-page":"e2024067675","DOI":"10.1542\/peds.2024-067675","article-title":"Late-onset sepsis among extremely preterm infants during the COVID-19 pandemic","volume":"155","author":"S Mukhopadhyay","year":"2025","journal-title":"Pediatrics"},{"issue":"19","key":"ref4","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1001\/jama.292.19.2357","article-title":"Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection","volume":"292","author":"B J Stoll","year":"2004","journal-title":"JAMA"},{"issue":"12","key":"ref5","first-page":"131","article-title":"Short- and long-term neurodevelopmental outcomes of very preterm infants with neonatal sepsis: a systematic review and meta-analysis","volume":"6","author":"S Cai","year":"2019","journal-title":"Children (Basel)"},{"issue":"04","key":"ref6","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1542\/peds.106.4.659","article-title":"The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability","volume":"106","author":"K Costeloe","year":"2000","journal-title":"Pediatrics"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s41669-020-00230-x","article-title":"Costs and extra length of stay because of neonatal bloodstream infection at a teaching hospital in Ghana","volume":"5","author":"A P Fenny","year":"2021","journal-title":"PharmacoEconom Open"},{"issue":"03","key":"ref8","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":"C Fleischmann-Struzek","year":"2018","journal-title":"Lancet Respir Med"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"S69","DOI":"10.1016\/S0378-3782(12)70019-1","article-title":"Early and late onset sepsis in very-low-birthweight infants from a large group of neonatal intensive care units","volume":"88","author":"C P Hornik","year":"2012","journal-title":"Early Hum Dev"},{"issue":"12","key":"ref10","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1097\/INF.0000000000004485","article-title":"Beyond early- and late-onset neonatal sepsis definitions: what are the current causes of neonatal sepsis globally? 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