Fever in neonates (infants ≤28 days old) is a serious clinical presentation that requires careful evaluation due to the risk of serious bacterial infection (SBI).
Approximately 4% of febrile infants, age 28 days or younger harbor invasive bacterial infections, specifically bacteria and bacterial meningitis.
In the US more than 70,000 infants are evaluated for fever within the first few months of life every year.
Fever: Rectal temperature ≥38°C (100.4°F)
Neonate: Birth to 28 days of age
Neonates have immature immune systems and often lack localizing signs of infection.
They’re at higher risk for: Bacteremia/sepsis Urinary tract infections Meningitis Pneumonia Osteomyelitis/septic arthritis
Common Pathogens Bacterial: Group B Streptococcus (GBS) Escherichia coli and other gram-negative organisms Listeria monocytogenes Streptococcus pneumoniae Staphylococcus aureus Viral-more common in older neonates Enteroviruses Herpes simplex virus (HSV) Respiratory viruses
Clinical approach to neonatal infections:
History: Birth history, maternal GBS status, feeding, urine output, exposures, sick contacts.
Thorough history and physical examination are essential, though fever is often the only sign of serious illness in young infants.
Key risk factors include age.
The epidemiology has shifted over recent decades, with decreased Group B streptococcus and Listeria infections but increased gram-negative organisms, particularly Escherichia coli.
Examination: Often nonspecific findings like lethargy, poor feeding, irritability, or respiratory distress
Risk Stratification: Rochester criteria, Philadelphia criteria, Step-by-Step approach that helps identify low-risk vs. high-risk infants
Testing:
Complete blood count with differential Blood culture Urinalysis and urine culture Lumbar puncture with CSF studies: routine lumbar punctures for all febrile infants, 28 days or younger to rule out bacterial meningitis.
Inflammatory markers enhance risk stratification.
The American Academy of Pediatrics recommends obtaining procalcitonin along with absolute neutrophil count or C-reactive protein.
Abnormal inflammatory markers are defined as: procalcitonin >0.5 ng/mL, CRP >20 mg/L, ANC >4000-5200/mm³, or temperature >38.5°C.
Sometimes: chest X-ray, stool studies, HSV testing, especially if vesicles, CSF pleocytosis, or maternal history is present.
Management:
The clinical approach to febrile neonates (infants ≤28 days old) requires a comprehensive sepsis evaluation, empiric parenteral antibiotics, and hospital admission, given the 1-4% risk of invasive bacterial infections-bacteremia and bacterial meningitis- that cannot be reliably identified by clinical examination alone.
Empiric antibiotics are typically started promptly (ampicillin + gentamicin or ampicillin + cefotaxime) while awaiting culture results, given the serious consequences of delayed treatment. Empiric intravenous antibiotics and hospitalization are indicated for all febrile neonates
Hospitalization is standard for most febrile neonates, particularly those <21-28 days.
Observation for 36-48 hours is adequate to identify nearly all infants with pathogenic organisms, as 96% of positive blood cultures become positive by 36 hours.
There is a with more conservative management for younger infants.
Viral testing (RSV, enterovirus, influenza) may inform management, particularly when positive results align with clinical presentation.
HSV evaluation should be considered with maternal history of genital HSV, vesicles, seizures, CSF pleocytosis without positive Gram stain, or elevated liver enzymes.
For infants 22-60 days old, clinical decision aids (PECARN, StepByStep, AAP guidelines) use sequential assessment incorporating age, clinical appearance, and inflammatory markers to identify low-risk infants in whom lumbar puncture and empiric antibiotics may be safely deferred.
These clinical decision approaches aim to reduce unnecessary invasive procedures while maintaining safety.
Modified criteria (Boston, Philadelphia, Rochester) exist for premature or medically complex infants presenting after 28 days of life.
A clinical prediction rule based (PECARN) on analysis of procalcitonin, an absolute neutrophil count can identify febrile young adults at low risk for bacteria, and or bacterial meningitis: using a prediction rule of laboratory test without lumbar puncture, has a high sensitivity, but more limited specificity for identifying febrile infants 28 days or younger with invasive bacterial infections.
Implementation of the PECARN clinical prediction rule to guide care in these patients can translate into tens of thousands of avoided lumbar puncture, antimicrobial courses, and hospitalizations every year.