Updates in Late-Onset Sepsis: Risk Assessment, Therapy, and Outcomes

Neoreviews. 2022 Nov 1;23(11):738-755. doi: 10.1542/neo.23-10-e738.


Neonatal late-onset sepsis (LOS) continues to threaten morbidity and mortality in the NICU and poses ongoing diagnostic and therapeutic challenges. Early recognition of clinical signs, rapid evaluation, and prompt initiation of treatment are critical to prevent life-threatening deterioration. Preterm infants-born at ever-decreasing gestational ages-are at particularly high risk for life-long morbidities and death. This changing NICU population necessitates continual reassessments of diagnostic and preventive measures and evidence-based treatment for LOS. The clinical presentation of LOS is varied and nonspecific. Despite ongoing research, reliable, specific laboratory biomarkers facilitating early diagnosis are lacking. These limitations drive an ongoing practice of liberal initiation of empiric antibiotics among infants with suspected LOS. Subsequent promotion of multidrug-resistant microorganisms threatens the future of antimicrobial therapy and puts preterm and chronically ill infants at even higher risk of nosocomial infection. Efforts to identify adjunctive therapies counteracting sepsis-driven hyperinflammation and sepsis-related functional immunosuppression are ongoing. However, most approaches have either failed to improve LOS prognosis or are not yet ready for clinical application. This article provides an overview of the epidemiology, risk factors, diagnostic tools, and treatment options of LOS in the context of increasing numbers of extremely preterm infants. It addresses the question of whether LOS could be identified earlier and more precisely to allow for earlier and more targeted therapy and discusses rational approaches to antibiotic therapy to avoid overuse. Finally, this review elucidates the necessity of long-term follow-up of infants with a history of LOS.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Neonatal Sepsis* / diagnosis
  • Neonatal Sepsis* / drug therapy
  • Neonatal Sepsis* / epidemiology
  • Risk Assessment
  • Sepsis* / diagnosis
  • Sepsis* / drug therapy


  • Anti-Bacterial Agents