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Fever and Sepsis Evaluation in the Neonate (0-28 days)

Pathway Background and Objective(s)

Neonates presenting with fever are at high risk of having and/or developing a serious bacterial infection. In addition, neonates can present with extensive HSV disease. Early identification and management is critical for improved outcomes. The AAP released a new clinical practice guideline in 2021 for febrile infants aged 8-60 days old that are well-appearing. These recommendations were carefully reviewed by our CT Children’s stakeholders in Infectious Disease and Immunology, Pediatric Hospital Medicine and the Emergency Department, and modified to meet the needs for our specific patient population. The management for febrile neonates who are 21 days or younger, or a neonate of any age that is ill-appearing is standardized to include blood, urine, CSF and HSV studies, with adequate empiric antimicrobials (including acyclovir). For the well-appearing neonate 22-28 days old, we have now recommended the consideration of deferring CSF studies if specific reassuring criteria are met. HSV studies and empiric acyclovir is only recommended based on HSV risk stratification in this group.

The objectives of this pathway are to:

  • Standardize initial work-up for neonates presenting with fever/sepsis
  • Decrease unnecessary variation in patient care based on current evidence
  • Provide guidelines for when to include HSV testing/treatment
  • Help guide appropriate antimicrobial therapy


Download Fever and Sepsis Evaluation in the Neonate Pathway Algorithm Updated January 20, 2023

Quality Metrics

  • % Patients with pathway order set
  • % HSV testing performed as indicated by pathway
  • % of patients with appropriate first line antibiotics received
  • % of patients with antibiotic administration within 2 hours of CSF collection time
  • % patients who receive acyclovir within 4 hours of HSV collection
  • ALOS (days)

Educational Module

Download Fever and Sepsis Evaluation in the Neonate Educational Module Updated January 20, 2023

Key References

  • Jain, et al. Management of Febrile Neonates in the US Pediatric Emergency Departments. 2014. Pediatrics. Volume 133, Issue 2.
  • American Academy of Pediatrics. Herpes Simplex. In: eds. Red Book: 2021-2024 Report of the Committee on Infectious Diseases. American Academy of Pediatrics; 2021; 407-417.
  • Pantell, R., et al. Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old. Pediatrics. August 2021, 148 (2) e2021052228; DOI:

Pathway Contacts

  • Melissa Held, MD
    • CT Children’s Infectious Diseases and Immunology
  • Grace Hong, APRN
    • CT Children’s Infectious Diseases and Immunology
  • Anand Sekaran, MD
    • CT Children’s Pediatric Hospital Medicine


The clinical pathways in the above links have been developed specifically for use at Connecticut Children’s and are made available publicly for informational and/or educational purposes only. The clinical pathways are not intended to be, nor are they, a substitute for individualized professional medical judgment, advice, diagnosis, or treatment. Although Connecticut Children’s makes all efforts to ensure the accuracy of the posted content, Connecticut Children’s makes no warranty of any kind as to the accuracy or completeness of the information or its fitness for use at any particular facility or in any individual case.

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