Managing a febrile 61-90 day old infant: A prediction rule

Introduction

We know how to evaluate febrile infants 0-60 days thanks to prior PECARN studies [1] and the American Academy of Pediatrics (AAP) recommendations [2], which identify infants who are at low risk (<1% risk of invasive bacterial infections). But what about the 61-90 days old febrile infant!? Invasive bacterial infections (bacteremia and/or bacterial meningitis) occur in approximately 1.5% of older infants [3, 4]. The PECARN study “Prediction Rule to Identify Febrile Infants 61-90 days at Low Risk for Invasive Bacterial Infections” published in Pediatrics proposes novel ways to identify low risk 61-90 days old febrile infants [5].

Study Design

Study Question: We aimed to derive and internally validate a clinical prediction rule to identify febrile infants aged 61–90 days at low risk of invasive bacterial infections (IBIs), with and without serum procalcitonin measurements.

  • Type of study: Secondary analysis of electronic health record data collected monthly from sites in the PECARN Registry.
  • Setting: 17 emergency departments across 10 U.S. health systems
  • Timeframe: January 1, 2012 – April 30, 2024.
  • Population: Infants 61–90 days old who presented with fever (≥38°C / 100.4°F) in the ED or at home or an outpatient clinic prior to the ED visit.
  • Inclusion criteria: Infants with fevers who had both a urinalysis/urine dipstick and blood culture obtained.
  • Exclusion criteria: Infants with substantial pre-existing conditions, prematurity (<=32 weeks), skin or soft tissue infections, home antibiotic use, or who were critically ill on arrival.
  • Sample size: 4,952 visits included with both a blood culture and urine studies
  • Outcome measured: Presence of invasive bacterial infections (IBI), defined as bacteremia and/or bacterial meningitis.

Methods:

  • Used Classification and Regression Tree (CART) analysis to derive 2 different clinical prediction rules.
  • The two models:
    1. Non-blood test rule: Included urinalysis results and maximum temperature
    2. Blood test rule: Incorporated procalcitonin (PCT) and absolute neutrophil count (ANC)
  • VALIDATED the two models: Internal cross validation

Results

Prevalence of invasive bacterial infections (IBIs):

  • 2% overall had IBIs.
  • 1.9% had bacteremia (bacteria in the blood).
  • 0.1% had bacterial meningitis.

Prediction Rules Derived and Validated:

1. Non–blood test rule (no blood work needed):

  • Low risk (<1% risk of invasive bacterial illness) if:
    • Urinalysis negative
    • Max temp ≤ 38.9°C (102°F)
  • Performance:
    • Negative predictive value (NPV): ~99.5%
    • Sensitivity: 86%
    • Specificity: 59%
    • Missed 14 infants with IBIs (not perfect sensitivity), including one with bacterial meningitis

2. Blood test rule (procalcitonin + absolute neutrophil count if you are drawing them):

  • Low risk if:
    • Procalcitonin ≤ 0.24 ng/mL
    • ANC ≤ 10,710/mm³
  • Performance:
    • NPV: 100%
    • Sensitivity: 100%
    • Specificity: 65.8% – Higher specificity than the non-blood test rule
  • Authors’ insight:
    • The higher ANC cutoff compared to the younger PECARN Febrile infant rule is likely due to (1) selection bias (sicker babies tended to get blood drawn) and (2) the appearance of pneumococcal infections in the 61-90 days old age group, which can elevate the ANC.

Clinical implications:

Not everyone is drawing labs on febrile 61-90 days old infants, and this study does not suggest you must draw labs. The lead author Dr. Aronson said:

We don’t want to increase blood testing in infants who the clinician is not considering obtaining blood testing, but rather our results provide evidence when these tests are obtained. The way we frame it is that IF you are going to obtain blood testing in this age group (which we are not saying you must), based on clinical judgment, height of fever, etc, those are the cutoffs to use.

The senior author Dr. Kuppermann said:

I use this in practice now because I do not typically obtain blood from these infants. If I do obtain blood, I now use those cutoffs for ANC and PCT. But the rules really should be validated before we push it hard to clinicians out there.

The next steps are to study these rules in a prospective, multi-center study. Additionally, prior study by the authors recently published in Pediatrics found a low risk of invasive bacterial infections in respiratory viral positive infants, and future study should also assess how viral testing impacts prediction rule performance [6].

Caution

Findings are promising but need prospective validation before becoming standard practice. Stay tuned!

Take Home Message

The study shows that while invasive bacterial infections in 61-90 days-old infants are infrequent (2%), clinicians can use simple urine and temperature measurements — and, if blood is obtained, specific lab cutoffs — to better identify which infants are at low risk, potentially reducing unnecessary hospitalizations and invasive testing in the future.

Why is this important for patients and caregivers

  • Guidelines on managing infants with fevers currently only cover those up to 60 days old. This leaves a dilemma when an older infant (61-90 days old) has a fever. Should we obtain blood labs from these infants? Lumbar punctures? Should we routinely administer antibiotics or hospitalize them? This study gives clinicians new, data-driven tools to help decide which infants are at low risk for life threatening bacterial infections.
  • Researchers analyzed nearly 5,000 ED visits for febrile infants aged 61–90 days across 17 children’s hospitals in PECARN nationwide (2012–2024). That volume of data makes the findings much more reliable.
  • Only about 2% of these infants had invasive bacterial infections (that is, in their blood or brain) which is a low rate but non-negligible. Knowing exactly how uncommon these infections are supports less aggressive decision-making and reassures parents and clinicians alike.
  • One day, these rules could mean fewer painful tests (like spinal taps), less time in the hospital, and less stress—all while keeping babies safe. However, doctors remind us these rules are not yet ready for routine use until they’re tested further in future studies.

References

  1. Kuppermann N, Dayan PS, Levine DA, et al; Febrile Infant Working Group of the Pediatric Emergency Care Applied Research Network (PECARN). A clinical prediction rule to identify febrile infants 60 days and younger at low risk for serious bacterial infections. JAMA Pediatr. 2019;173(4):342–351. PubMed doi: 10.1001/jamapediatrics.2018.5501
  2. Pantell RH, Roberts KB, Adams WG, et al; Subcommittee on Febrile Infants. Evaluation and management of well-appearing febrile infants 8 to 60 days old. Pediatrics. 2021;148(2):e2021052228. PubMed doi: 10.1542/peds.2021-052228
  3. Aronson PL, Thurm C, Alpern ER, et al; Febrile Young Infant Research Collaborative. Variation in care of the febrile young infant <90 days in US pediatric emergency departments. Pediatrics. 2014;134(4):667–677. PubMed doi: 10.1542/peds.2014-138
  4. Gomez B, Mintegi S, Bressan S, Da Dalt L, Gervaix A, Lacroix L; European Group for Validation of the Step-by-Step Approach. Validation of the “step-by-step” approach in the management of young febrile infants. Pediatrics. 2016;138(2):e20154381. PubMed doi: 10.1542/peds.2015-4381
  5. Aronson PL, Mahajan P, Meeks HD, Nielsen B, Olsen CS, Casper TC, Grundmeier RW, Kuppermann N; PECARN Registry Working Group. Prediction Rule to Identify Febrile Infants 61-90 Days at Low Risk for Invasive Bacterial Infections. Pediatrics. 2025 Aug 26:e2025071666. doi: 10.1542/peds.2025-071666. Epub ahead of print. PMID: 40854562.
  6. Aronson PL, Mahajan P, Nielsen B, Olsen CS, Meeks HD, Grundmeier RW, Kuppermann N; PECARN Registry Working Group. Risk of Bacterial Infections in Febrile Infants 61 to 90 Days Old With Respiratory Viruses. Pediatrics. 2025 Jul 1;156(1):e2025070617. doi: 10.1542/peds.2025-070617. PMID: 40506050; PMCID: PMC12410455.
Julia Magaña

Julia Magaña

University of California, Davis

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