Should fever be treated in neonates?

Management of Fever in Neonates

Febrile neonates should be hospitalized for a full sepsis evaluation and receive empiric antimicrobial therapy while awaiting culture results, due to their high risk of serious bacterial infections and potentially devastating outcomes if treatment is delayed. 1

Risk Assessment in Neonates with Fever

Neonates (infants ≤28 days old) with fever represent a high-risk population due to:

• Immature immune system making them vulnerable to serious bacterial infections
• Higher incidence of bacteremia, meningitis, and urinary tract infections
• Limited clinical signs that may not reflect the severity of underlying infection
• Potential for rapid clinical deterioration

According to the 2021 AAP guidelines, fever in neonates requires aggressive evaluation and management due to the significant risk of serious bacterial infections (SBIs) 1. Studies have shown that in the pre-pneumococcal vaccine era, the risk of SBI in neonates was approximately 13%, with bacteremia and meningitis occurring in a significant percentage of cases 1.

Diagnostic Approach

For febrile neonates, a complete sepsis workup should include:

• Blood culture
• Urine culture (obtained by catheterization or suprapubic aspiration)
• Cerebrospinal fluid (CSF) analysis and culture
• Complete blood count with differential
• Inflammatory markers (e.g., C-reactive protein)

The 2021 AAP guidelines emphasize that CSF analysis is critical in neonates with fever, as bacterial meningitis may present with minimal clinical signs 1. In a study of over 3,000 febrile infants, only 58% of those with bacteremia or bacterial meningitis appeared clinically ill 1.

Treatment Recommendations

Initial Management:

1. Hospitalize all febrile neonates regardless of clinical appearance
2. Initiate empiric antimicrobial therapy after cultures are obtained
   • Recommended regimen: ampicillin and gentamicin 2
   • Continue until culture results are available (typically 24-36 hours)

Subsequent Management:

• If cultures remain negative after 24-36 hours and the infant is clinically well or improving:

  • Discontinue antimicrobial therapy
  • Consider discharge if there are no other reasons for hospitalization 1

• If cultures are positive or the infant's condition deteriorates:

  • Adjust antimicrobial therapy based on culture results and susceptibilities
  • Continue treatment for the appropriate duration based on the identified infection

Special Considerations

Viral Infections

Even when a viral infection is suspected, empiric antimicrobial therapy should still be initiated in neonates with fever while awaiting culture results 1. The presence of a viral infection does not exclude the possibility of a concurrent bacterial infection 1.

Herpes Simplex Virus (HSV)

Consider HSV testing and empiric acyclovir in neonates with fever, especially if there are risk factors for HSV infection or if bacterial cultures remain negative. Studies have shown that neonatal HSV can present with fever alone, similar to bacterial meningitis 3.

Common Pitfalls to Avoid

1. Deferring lumbar puncture: CSF analysis is essential in the evaluation of febrile neonates, as meningitis may present with minimal clinical signs.

2. Relying solely on clinical appearance: Even well-appearing neonates with fever can have serious bacterial infections. The AAP guidelines emphasize that clinical appearance alone is insufficient to rule out SBI in this age group 1.

3. Withholding empiric antibiotics: Delaying antimicrobial therapy in febrile neonates while awaiting culture results can lead to increased morbidity and mortality if a bacterial infection is present.

4. Treating fever without addressing the underlying cause: While antipyretics may provide symptomatic relief, they do not treat the underlying infection. The focus should be on identifying and treating the cause of fever rather than just reducing the temperature 4.

5. Early discharge without adequate observation: Neonates with fever should be hospitalized for close monitoring and completion of the diagnostic evaluation, even if initial laboratory results are reassuring.

In summary, fever in neonates requires prompt hospitalization, complete sepsis evaluation including CSF analysis, and empiric antimicrobial therapy while awaiting culture results. This aggressive approach is justified by the high risk of serious bacterial infections in this vulnerable population and the potential for rapid clinical deterioration if treatment is delayed.