What is the next step in managing a 25-day-old newborn with fever and fussiness?

Management of a 25-Day-Old Febrile Newborn

The correct next step for this 25-day-old newborn with fever (38.4°C) is full sepsis evaluation including blood, urine, and cerebrospinal fluid cultures, followed by hospitalization and empiric parenteral antimicrobial therapy with ampicillin and either ceftazidime or gentamicin.

Initial Assessment and Risk Stratification

• This 25-day-old infant falls into the high-risk age group (≤28 days) where fever (≥38.0°C) requires a complete sepsis workup regardless of clinical appearance 1
• Even though the infant appears well with normal vital signs (except for fever and mild tachycardia), well-appearing febrile neonates can still have serious bacterial infections (SBIs) 1, 2
• In a study of over 3,000 febrile infants, only 58% of those with bacteremia or bacterial meningitis appeared clinically ill 1
• The risk of serious bacterial infection in neonates (aged 3-28 days) is approximately 13%, which is significantly higher than older infants 1

Required Diagnostic Evaluation

• Complete blood count with differential 1
• Blood culture 1
• Urinalysis and urine culture (via catheterization) 1, 2
• Cerebrospinal fluid (CSF) analysis and culture 1
• Consider chest radiograph if respiratory symptoms develop 2

Importance of Cerebrospinal Fluid Analysis

• For infants 22-28 days old, CSF analysis is essential even with normal urinalysis and inflammatory markers 1
• Without CSF analysis, the risk of missing bacterial meningitis is significant, and hospitalization would be mandatory 1
• Bacterial meningitis in this age group has a prevalence of 0.4% to 0.6%, with potentially devastating consequences if missed 1

Treatment Approach

• Initiate empiric parenteral antimicrobial therapy immediately after cultures are obtained 1
• For a 25-day-old infant, the recommended regimen is: 1
  • Ampicillin IV or IM (150 mg/kg/day divided every 8 hours) 3 AND
  • Either ceftazidime IV or IM (150 mg/kg/day divided every 8 hours) OR
  • Gentamicin IV or IM (4 mg/kg/dose every 24 hours) 4

Hospitalization Requirements

• All febrile infants ≤28 days of age should be hospitalized for observation and parenteral antibiotics, regardless of laboratory findings or clinical appearance 1
• Hospitalization should be in a facility with nurses and staff experienced in the care of neonates/young infants 1
• Outpatient management is not appropriate for this age group, even if the infant appears well 1, 5

Duration of Treatment and Follow-up

• Continue empiric antibiotics until culture results are available (typically 24-48 hours) 1
• If cultures remain negative and the infant is clinically well or improving, antibiotics may be discontinued after 36-48 hours 1
• If a bacterial pathogen is identified, targeted antimicrobial therapy should be continued for the appropriate duration based on the specific infection 1

Common Pitfalls to Avoid

• Delaying lumbar puncture or antibiotics due to the well appearance of the infant 1, 2
• Relying solely on inflammatory markers (WBC, CRP, ESR) to rule out serious bacterial infection, as these have limited sensitivity in this age group 6
• Treating with oral antibiotics or managing as an outpatient, which is inappropriate for this age group 1
• Failing to recognize that fever in neonates is often the only sign of serious bacterial infection 7, 8
• Dismissing the significance of fever reported by parents but not documented in the clinical setting 9

Special Considerations

• The most common serious bacterial infection in this age group is urinary tract infection, followed by bacteremia and meningitis 10
• Even if a viral infection is suspected, bacterial co-infection cannot be ruled out without appropriate testing 1, 2
• The risk of serious bacterial infection is higher in neonates with documented fever (as in this case) compared to those with fever by history only 9