Can you trust a febrile infant?

“No” has been, and continues to be, the resounding answer over the last 40 years as researchers and clinicians work to determine the optimal evaluation and management of the well-appearing young febrile infant [1].

The goal remains to identify infants with bacterial infections in this at-risk cohort of patients while also considering the balance of cost-effectiveness on a population scale and the potential for iatrogenic harm with evaluation such as unnecessary lumbar punctures, unnecessary antibiotics, and unnecessary hospitalization. Fortunately, bacteremia and bacterial meningitis in this age group are uncommon [2]. Unfortunately, delayed or missed diagnosis can be devastating [1-3].

In the most recent 2021 Clinical Practice Guideline, the American Academy of Pediatrics (AAP) aims to provide guidance with 3 separate age-based algorithms for the evaluation and management of the well-appearing febrile infant [4]. These guidelines were made possible by the recent PECARN, Step by Step, and other studies and the invaluable information they have provided [5-7].

Who’s included?

• Well-appearing febrile infants
  • The AAP acknowledges that clinician experience is likely the best determinate of what is “well-appearing”, further admitting that there is no measure or definition of either “experience” or “well-appearing”
•  Febrile
  • Rectal temperatures of  38.0C or 100.4F at home in the past 24 hours or determined in a clinical setting
  • Subjective fevers at home are excluded
•  Gestation
  • Between 37-42 weeks
  • Premature infants excluded
• Age
  • Days 8 to 60 and have been discharged home following birth

Who is not included?

• Preterm or infants with congenital/chromosomal abnormalities
• Infants with focal bacterial infections
• Cellulitis, omphalitis, septic arthritis, osteomyelitis
•  Bronchiolitis
  • With or without a positive RSV test
•  Immunocompromised
  • Either suspected or known deficiency
• Immunizations in the previous 48 hours

It should also be noted that the AAP has named the following as high-risk inflammatory markers that will be referenced in the soon-to-be-discussed guidelines [4,5].

• Temperature >101.3F (38.5C)
• C-reactive protein (CRP) > 20 mg/L
• Procalcitonin >0.5 ng/mL
• Absolute neutrophil count (ANC) >4000 mm³  (or 5200 mm³ if your facility does not have procalcitonin available)

The Groups

Conclusion

Over the course of nearly the last half century there has been a lack of clear evidence-based guidelines in evaluating the young febrile infant [1]. Although serious bacterial infections in these young, febrile infants are uncommon, studies show that in the first month of life, bacteremia can be present in nearly 3% of febrile infants, with bacterial meningitis occurring in about 1% [2]. The absence of consensus regarding management has led to significant costs due to hospitalizations and their associated iatrogenic complications [9]. In the movement to create new recommendations, shifting epidemiology pushed changes in previous guidelines with a new focus on the use of the now widely available inflammatory markers [10].  With the advent of multiple large-scale studies and the recent improvements in lab testing, the newly updated AAP guidelines provide recommendations on how to manage this challenging population [4-7].

Take Home Points

• These management strategies can only be used in WELL-APPEARING infants – if they’re ill-appearing, do a complete workup.
• Evaluation of febrile infants 0-21 days remains the same – do everything (blood culture, UA +/- culture, LP with CSF studies), give antibiotics, and admit.
• For those infants 22-28 days, get the UA, blood culture, and inflammatory markers to guide management.
  • Not all febrile infants in the 22-28 day subset need an LP, though it should still be obtained in certain clinical circumstances, and discussed between  provider and parents in other situations
• In infants ≤28 days, a complete workup is still needed even if a viral source is present.
• Febrile infants 29-60 days old may be sent home after a negative workup with close follow-up.