What is the appropriate management for fever in a neonate?

Management of Fever in Neonates

All febrile neonates (≤28 days old) require immediate hospitalization, full sepsis workup including blood culture, urinalysis with urine culture via catheterization, lumbar puncture for cerebrospinal fluid analysis, and empiric parenteral antibiotic therapy before culture results return. 1, 2, 3

Definition and Temperature Measurement

• Fever is defined as rectal temperature ≥38.0°C (100.4°F), documented either in the clinical setting or at home within the past 24 hours 1, 2
• Rectal temperature is mandatory in neonates—it is the only acceptable method as it provides the closest approximation to core body temperature and maximizes sensitivity for detecting serious bacterial infections 1, 2, 3
• Never rely on axillary, oral, tympanic, or temporal artery measurements in neonates, as these have lower reliability and the stakes of missing serious bacterial infection are too high 3
• Verify accuracy of home temperature measurements, as antipyretic use within the previous 4 hours may mask fever severity 1, 4

Risk Assessment in Neonates

• Neonates (≤28 days) carry a 13% risk of serious bacterial infection (SBI), the highest of any pediatric age group 1
• Only 58% of neonates with bacteremia or bacterial meningitis appear clinically ill, making clinical appearance alone unreliable for risk stratification 1, 2
• The most common SBI in neonates is urinary tract infection, but bacteremia and bacterial meningitis remain significant threats requiring aggressive evaluation 1, 5
• Exposure to bacterial pathogens during the perinatal period and lack of vaccine-based immunity place neonates at uniquely high risk 1

Mandatory Diagnostic Workup

Complete the following before initiating antibiotics:

• Blood culture to detect bacteremia 1, 2, 6
• Complete blood count with differential to assess for leukocytosis, neutrophilia, or bandemia 2, 6
• Urinalysis and urine culture via catheterization—never use bag specimens due to high contamination rates 1, 2
• Lumbar puncture for cerebrospinal fluid analysis including cell count, glucose, protein, Gram stain, and bacterial culture 1, 2, 6
• Consider inflammatory markers (C-reactive protein, procalcitonin) to augment risk assessment, though these should not delay antibiotic administration 1, 2

Empiric Antibiotic Therapy

• Initiate parenteral antibiotics immediately after obtaining cultures 1, 2, 6
• Standard regimen: ampicillin plus gentamicin to cover group B streptococcus, Escherichia coli, Listeria monocytogenes, and other gram-negative organisms 7, 6
• Gentamicin is indicated for bacterial neonatal sepsis and serious bacterial infections of the central nervous system, urinary tract, and other sites 7
• In neonates with suspected bacterial sepsis or staphylococcal pneumonia, a penicillin-type drug (ampicillin) is indicated as concomitant therapy with gentamicin 7
• Consider adding acyclovir if herpes simplex virus infection is suspected, particularly with altered mental status, seizures, or CSF pleocytosis without positive bacterial culture 1, 6

Hospitalization and Monitoring

• All febrile neonates require hospital admission regardless of clinical appearance 1, 2, 8, 6
• Continue parenteral antibiotics until culture results return and clinical status is reassessed 2, 6
• If cultures are negative at 48-72 hours and the neonate is clinically well, antibiotics may be discontinued and the infant observed or discharged with close follow-up 8, 6
• If any culture is positive, complete the appropriate antibiotic course based on the identified organism and site of infection 2

Critical Pitfalls to Avoid

• Never discharge a febrile neonate without full sepsis workup and hospitalization, even if the infant appears well—clinical appearance is unreliable in this age group 1, 2
• Do not delay lumbar puncture due to concerns about procedural risk; bacterial meningitis carries devastating morbidity and mortality if untreated 1, 2, 6
• Never assume a viral infection (even if documented by rapid testing) excludes coexisting bacterial infection—the presence of viral illness does not preclude SBI 1, 4
• Do not rely on home temperature measurements alone without confirming rectal temperature in the clinical setting 1, 2
• Avoid using bag-collected urine specimens, as contamination rates are unacceptably high and may lead to unnecessary antibiotic treatment 1, 2

Special Considerations

• Maternal fever during labor increases the risk of perinatal respiratory depression, neonatal seizures, and mortality in the neonate, warranting heightened vigilance 1
• Hypothermia or normal temperature does not exclude serious infection in neonates—maintain a high index of suspicion regardless of measured temperature 1
• Immunization status is not relevant in neonates, as they have not yet received protective vaccines 1