Management of Neonatal Fever
The recommended first-line treatment for neonatal fever is ampicillin plus gentamicin, which should be initiated immediately after appropriate cultures are obtained. 1, 2
Initial Assessment and Workup
For a febrile neonate (defined as temperature ≥38°C or 100.4°F), the following workup is essential:
- Complete blood count with differential
- Blood culture
- Urinalysis and urine culture
- Cerebrospinal fluid (CSF) analysis and culture
- Chest X-ray if respiratory symptoms are present
Age-Based Empiric Antibiotic Therapy
Neonates 0-7 days old (≤34 weeks gestational age)
Neonates 0-7 days old (>34 weeks gestational age)
Neonates 8-28 days old (≤34 weeks gestational age)
Neonates 8-28 days old (>34 weeks gestational age)
Neonates 29-60 days old
- Ceftriaxone: 50 mg/kg/dose every 24 hours 1
Treatment Based on Suspected Source of Infection
No Focus Identified (Possible Bacteremia)
- 0-28 days: Ampicillin + gentamicin as dosed above
- 29-60 days: Ceftriaxone 50 mg/kg/dose every 24 hours 1
Urinary Tract Infection
- 0-28 days: Ampicillin + gentamicin as dosed above
- >28 days: Ceftriaxone 50 mg/kg/dose every 24 hours or oral cephalexin (50-100 mg/kg/day in 4 doses) for well-appearing infants 1
Bacterial Meningitis
- 0-28 days: Ampicillin (300 mg/kg/day divided every 6 hours) + ceftazidime (150 mg/kg/day divided every 8 hours)
- 29-60 days: Ceftriaxone (100 mg/kg/day once daily or divided every 12 hours) 1
Duration of Treatment
- Culture-negative sepsis: 7-10 days
- Culture-positive sepsis: 10-14 days
- Bacterial meningitis: 14-21 days
- Urinary tract infection: 10-14 days
Monitoring During Treatment
- Daily clinical assessment for signs of improvement or deterioration
- Monitor gentamicin levels (peak and trough) after the third dose
- Target peak: 5-10 μg/mL
- Target trough: <2 μg/mL 5
- Monitor renal function with serum creatinine
- Consider once-daily gentamicin dosing (4 mg/kg/day) which has shown equivalent efficacy with potentially less toxicity 6, 5
Important Considerations
Do not delay antibiotics while waiting for cultures in a febrile neonate. Cultures should be obtained first when possible, but treatment should not be delayed more than 1 hour 2.
Avoid empiric use of ampicillin + cefotaxime as this combination has been associated with increased risk of neonatal death compared to ampicillin + gentamicin 7.
Antimicrobial resistance concerns: In low and middle-income countries, there is increasing resistance to ampicillin and gentamicin among Gram-negative bacteria. Local antibiograms should guide therapy in these settings 1.
De-escalation: Once culture results are available, narrow antibiotic coverage based on identified pathogens and susceptibilities 2.
Hospitalization: All febrile neonates should be hospitalized for parenteral antibiotics and close monitoring, even those who appear well 1.
Special populations: For neonates with immune compromise or at high risk for multidrug-resistant pathogens, broader empiric coverage may be necessary 2.
The combination of ampicillin and gentamicin remains the most appropriate empiric therapy for neonatal fever in most settings, providing adequate coverage against the most common pathogens while minimizing the risk of antimicrobial resistance and adverse effects 8.