Febrile infants!


There is A LOT of literature out there about febrile infants. Here’s a great JAMA Peds review to get your temperature up and running. 

The incidence of serious bacterial infection (SBI) in kids <3 months-old is 9-14%!

  • SBI includes UTI, pneumonia, bacteremia, osteomyelitis, meningitis, etc.

Neonates <28 days old are at higher risk of SBI than infants aged 28-90 days.

  • Neonatal sepsis refers to sepsis in kids <28 days old
  • Early-onset neonatal sepsis in kids <7 days-old
  • Late-onset neonatal sepsis in 7-28 day-old kids


  • You can thank 1800s psychiatrist Dr. Carl Reinhold August Wunderlich for defining fever as a temperature above 100.4º
  • Before universal vaccination for Hib and S.pneumoniae, 3-15% of older infants and toddlers presenting with fever had bacteremia. 
  • Universal vaccination has caused a shift in SBI over time. Before 2000, there was a higher proportion of bacteremia and meningitis, while UTI accounted for 30-55% of SBI. Today UTI accounts for 75-84% of SBI, making E.coli the most common cause of SBI in infants. 


  • The rate of neonatal sepsis increases with decreasing gestational age and decreasing birth weight, so it’s important to reclassify preterm kids with their corrected age. For instance, a febrile 7-wk-old ex-35-wk baby has a similar risk as a febrile 2-wk-old ex-40-wk baby. 
  • Neonates may be at higher risk of SBI due to immature T-cells, which express less CD40, creating a relative immunodeficiency!
  • In the presence of pathogenic bacteria, 91% of blood cultures are positive by 24 hours, 96% by 36 hours, and 99% by 48 hours. Hence, the old “48 hour rule out” may be a “Thing We Do For No Reason
  • Multiple criteria exist to stratify febrile infants at low risk for SBI, but vary in terms of age, history, and labs: Rochester, Philadelphia, PECARN, Step-by-Step etc.
    • The Rochester criteria is often used because it includes neonates ≤28 days-old, does not require an LP, and has a negative predictive value above 98%; however the general recommendation is that all febrile neonates ≤28 days-old undergo a full sepsis evaluation including LP because these infants are considered NOT low risk based on age alone
    • PECARN and Step-by-step require procalcitonin


Typically presents in the first 4 weeks of life, but may present up to 7 weeks of age.

3 disease manifestations: SEM (45%), CNS disease (30%), and disseminated disease (25%).

  • If untreated, SEM has a high risk of progressing to CNS or disseminated disease

Red Book pearl: “History of maternal genital HSV infection is not helpful in diagnosing neonatal HSV disease because more than three quarters of infants who contract HSV infection are born to women with no history or clinical findings suggestive of genital HSV infection during or preceding pregnancy and who, therefore, are unaware of their infection.” 

3 essential screening tests for HSV: 1) plasma PCR, 2) surface PCR, and 3) CSF PCR

  • Surface PCR includes swab of eyes, nares, mouth, and anus
  • If vesicles are present, then also get PCR/DFA of unroofed lesion


  • What are the risk factors for neonatal sepsis?
  • Besides fever, what other symptoms should prompt a work-up for neonatal sepsis?
  • What work-up should we do in febrile infants? Does it vary by age or vaccine status?
  • Should we ever attribute a fever to swaddling or bundling?
  • What are some non-infectious causes of fever in infants?
    • malignancy (leukemia, lymphoma, neuroblastoma), Kawasaki/vasculitis, hyperthyroidism, Rx (salicylate/iron overdose, sympathomimetics, serotonin sn, NMS, MH)
  • What’s the risk of SBI in kids with an apparent viral syndrome? Should we routinely LP neonates with clinical bronchiolitis?
  • What are the most common bacterial causes of SBI in infants <3mo? 
  • Why do we always use ampicillin and gentamicin? 
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