It is often said that parents may miss a lot of things that are going on with their children (being a parent, I can attest to this), but they will never miss a fever. Certainly, fever catches our attention also as we know that we must remain vigilant for very treacherous things like Neutropenic Fever, Central Line Infections, and the Febrile patient with Sickle Cell Disease; however, the topic that still garners the most conversation and attention is fever in the otherwise well appearing infant. You would think that we would have a very solid grip on the topic. Alas, it still seems to be a moving target that can be challenging to even the most “seasoned” of providers. We recently discussed the Roseville Criteria for the evaluation of the youngest of children (0-60 days) and it may have seen to be a little “cutting edge” and perhaps you weren’t quite ready to embrace it. Understandable. Evolution of information and our personal and professional growth can often challenge even the most solid of doctrine. To continue with this notion of continued evolution, though, the American Academy of Pediatrics (AAP) published a new set of guidelines with respect to the Evaluation and Management of the Well-Appearing Febrile Infant [Pantell, 2021, PMID 34281996]. Let’s take a moment to digest a small portion of that guideline (let’s say, a morsel of it) and look at what is the most current recommendation for those Febrile Infants 29 to 60 days of age.

Febrile Infants 29 to 60 Days: Historic Perspective

Bacterial infections in infants are bad, but bacteriology is changing [Pantell, 2021, PMID 34281996]

• Group B Strep can lead to rapid and progressive illness, even when lab studies were unexciting.
  • GBS had been the most dominant bacterial infection in the first few weeks of life…
  • Fortunately, now prenatal GBS screening and treatment has reduced GBS’s impact.

• Listeria monocytogenes – yes, it needs to be considered, but better regulations on food safety and education has helped to reduce its impact as well and it is now rare in the US.

• Escherichia coli is now the most common organism found in infants 1 to 60 days of life.

• Decision models that were constructed based on prior infection epidemiology (Gram-positive predominance previously; Gram-negative prevalence today) can lead to errors.

Testing has evolved… [Pantell, 2021, PMID 34281996]

• The WBC count, ANC count, Band count, and Urinalysis were the prior tools of risk stratification.
  • We all now know how the WBC count performs poorly (and is the “Last Bastion of the Intellectually Destitute”).
  • These are even less useful now with E. coli being the most prevalent pathogen in this age group.
  • The original values (like WBC count of >5 and <15) were also arbitrary.

• Other Inflammatory Markers (IM) are now more useful.
  • No single IM on its own is reliable enough for risk stratification so combinations of them are advocated for.
  • ANC count is still used (although also arbitrary in its values) as it is more available than procalcitonin.
    • >4,000 (or >5,200) is abnormal (depending on the reference you are using)
    • < 1,000 is also concerning for evolving sepsis.
  • C-reactive Protein
    • Produced by the liver in response to infections (and several other conditions)
    • Widely available and even as a point-of-care test
    • >/= 20 mg/L is abnormal for this guideline.
  • Procalcitonin
    • Produced rapidly in response to infection and tissue injury.
    • Found to be more specific for bacterial infections than any other IM currently used.
    • Currently considered the most accurate IM for risk stratification … but…
    • It is not as readily available in all hospitals and may not be available at all hours.
    • >0.5 ng/mL is abnormal for this guideline.
• Pathogen Detection is also improving.
  • There are more tests available that are able to rapidly identify specific bacteria, viruses, and fungi.
  • Some are able to provide results within one hour!

In the end, the goal is to provide the appropriate care for those at risk.

• Knowing the inherent risks of meningitis, bacteremia, and UTI we clearly want to determine who is at risk for having these conditions.
• Accurate risk stratification is imperative!
  • It is how we determine who may benefit from therapies / hospitalization and, therefore, are able to offset the inherent risk associated with those therapies and hospitalizations.
  • It is also how we find those patients in whom the risk of the therapies / hospitalizations are greater than the chance of benefiting from them.

Febrile Infants 29 to 60 Days: Updated Guideline

The newly published AAP guideline [Pantell, 2021, PMID 34281996] discusses numerous important points. Here will will highlight a few… but I encourage you to actually read the detailed guideline as well.

• This guideline applies to:
  • Well appearing infants who have…
  • Rectal temperature of 100.4 F or higher at home or in the past 24 hours and who had…
  • Between 37 and 42 weeks gestation and now are…
  • Between 8 and 60 days of age

• Recommendations are broken down further for:
  • Infants 8 to 21 days of age
  • Infants 22 to 28 days of age
  • Infants 29 to 60 days of age (we will address this group here… perhaps the others later)

Some things stay the same: [Pantell, 2021, PMID 34281996]

• Get the blood culture
  • The prevalence of bacteremia is lower in this group than in the younger infants, but still warrants a blood culture.

• Get screening Inflammatory Markers (IM)
  • While a social smile may be present (and that makes me smile), we cannot rely solely on our physical exam in this age group.

• Get a Urinalysis
  • UTI is still the most commonly encountered infection in this age group.

• You may decide to get CSF…
  • This will be based on your own personal risk-tolerance… and also that of the parents (always good to involve them in the discussion also).
  • If all IMs are normal, then an LP is unlikely to be helpful… EVEN IF THE URINE IS ABNORMAL (concurrent UTI and Meningitis in this age group is low — we have known this).
  • Abnormal IMs that are exceedingly high (or low) does increase the risk of bacterial meningitis.
  • This is similar to our most recent practice as well.

• If IMs are normal and Urinalysis is normal, then no LP, no antibiotics, and no need for admission. Follow-up in 24 hrs is still appropriate.

• If IMs are normal and Urinalysis is abnormal, send the Urine Culture and treat with oral antibiotics (for presumptive UTI).

Some things have changed: [Pantell, 2021, PMID 34281996]

• You may decide to obtain Urinalysis from a Bag!
  • Ok…. I admit… this hurts my sensibilities a little… but I’m strong enough to say I will attempt to change my ways (please hold my hand someone!).
  • The rate of positive urine culture results without an abnormal urinalysis is roughly the same as the rate of asymptomatic bacteriuria.
    • Ok… this makes sense… UTI (by definition today) requires both growth of a uropathogen AND leukocytes in the urine.
    • So… you can get the Urinalysis first and if it is normal no Urine culture is required (this may take some getting used to).
  • It is acceptable to perform urinalysis off of urine obtained from a sterile specimen bag or stimulated void! This sample cannot be sent for culture though.
  • If the results are abnormal, THEN a urine sample needs to be obtained via catheterization or suprapubic aspiration.
    • So it may become a “two-step” process… but… may also lead to many less children having painful urethral catheterizations!

• The Inflammatory Markers (IM) have changed:
  • If Procalcitonin is available, then obtain either CRP or ANC.
  • If Procalcitonin is not easily available, then obtain CRP and ANC.
  • Abnormal IMs are:
    • Temperature > 38.5C (101.3F)
    • Procalcitonin > 0.5 ng/mL
    • CRP > 20 mg/L
    • ANC > 4,000 to 5,000mm^3

• Abnormal IMs does not equate to automatic LP.
  • It is reasonable to observe these (29-60 day old) well-appearing infants without performing an LP.
  • The guideline actually even notes that you may give parenteral antibiotics… here is where I may remain more conservative and either ensure I get the CSF and give antibiotics or observe without antibiotics.

Moral of the Morsel

• Times (and Bacterial Epidemiology) are a Changing! While you may feel comfortable with your strategy for evaluation and management of the febrile infant, recognize that much of what we “knew” before were estimates based on prior bacterial risks. As the strategies to avoid those risks (ex, GBS prophlyaxis) have evolved, so too will our need to evolve our practice.

• WBC Count is still the Last Bastion of the Intellectually Destitute. Always has been and seems like it will remain as such.

• Try to convince your hospital to invest in tomorrow’s technology today. Procalcitonin and better specific markers for individual pathogens will help us better treat our patients in the future.

References