Management of Fever in Neonates (0-28 Days)
All febrile neonates (≤28 days old) with temperature ≥38.0°C require immediate hospitalization, complete sepsis workup including lumbar puncture, and empirical intravenous antibiotics before culture results return. 1, 2, 3
Immediate Diagnostic Workup
Complete sepsis evaluation is mandatory for all neonates and includes:
- Blood culture (obtained before antibiotics) 1, 2
- Urinalysis and urine culture via catheterization or suprapubic aspiration (never bag collection) 1, 2, 4
- Lumbar puncture for CSF analysis and culture - this is non-negotiable in neonates regardless of appearance 1, 2, 5
- Complete blood count with differential 2, 6
- Inflammatory markers (CRP and/or procalcitonin) 2
- Chest radiograph only if respiratory symptoms present (cough, tachypnea, hypoxia, rales) 2, 4
The rationale is clear: neonates under 28 days are at highest risk for invasive bacterial infections (13% incidence of serious bacterial infection), with delayed diagnosis associated with increased morbidity and mortality. 2, 7 Physical examination alone cannot reliably exclude serious bacterial infection in this age group. 2
Empirical Antibiotic Therapy
Initiate antibiotics immediately after obtaining cultures:
- Ampicillin PLUS Gentamicin is the standard empirical regimen for neonatal sepsis 8, 5, 6
- Ampicillin dosing for neonates ≤28 days with bacterial meningitis/septicemia: 8
- Gestational age ≤34 weeks AND postnatal age ≤7 days: 100 mg/kg/day divided every 12 hours
- Gestational age ≤34 weeks AND postnatal age 8-28 days: 150 mg/kg/day divided every 12 hours
- Gestational age >34 weeks AND postnatal age ≤28 days: 150 mg/kg/day divided every 8 hours
- Consider adding acyclovir if any concern for herpes simplex virus (maternal history, vesicular lesions, CSF pleocytosis with negative Gram stain, seizures) 3, 6
The combination of ampicillin and gentamicin provides coverage for the most common neonatal pathogens: E. coli (60% of bacteremia, 87.4% of UTI, 43.7% of meningitis), Group B Streptococcus, and Listeria monocytogenes. 1, 5
Hospitalization Requirements
All neonates must be hospitalized in a facility with:
- Nurses and staff experienced in neonatal care 1
- Capability for continuous monitoring 1
- Immediate access to pediatric specialists 1
Duration of Antibiotics and Discharge Criteria
Discontinue antibiotics and discharge after 24-36 hours if ALL of the following are met:
- Infant is clinically well or improving (afebrile, feeding well) 1
- All cultures (blood, urine, CSF) remain negative at 24-36 hours 1
- No other infection requiring treatment 1
Note that bacterial pathogens may not be detected by 24 hours in 15-18% of cases and longer than 36 hours in 5-7% of cases, which is why the 24-36 hour observation period is critical. 1
If cultures are positive, treat with targeted antimicrobial therapy for duration appropriate to the organism and site of infection (typically 7-10 days for bacteremia, 14-21 days for meningitis). 1
Common Pitfalls to Avoid
- Never rely on clinical appearance alone - even well-appearing neonates can have serious bacterial infection 2, 3
- Never skip lumbar puncture in neonates, even if other tests are normal 1, 2
- Never use bag-collected urine specimens - contamination rates are unacceptably high; only catheterization or suprapubic aspiration are acceptable 2, 4
- Never delay antibiotics while waiting for culture results in neonates 3, 6
- Never administer antibiotics before obtaining cultures as this may obscure diagnosis 2, 6
Key Epidemiologic Changes
The epidemiology has shifted significantly with widespread vaccination against S. pneumoniae and H. influenzae type b. 1, 6 Urinary tract infections now represent the most common serious bacterial infection (5-7% overall prevalence, up to 20% in uncircumcised male infants), with E. coli as the predominant pathogen. 1, 2 Multiple sites of infection occur in 9% of patients, with 52% of bacteremia associated with urinary tract infections. 1