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Reference: Burstein B, et al. Prediction of Bacteremia and Bacterial Meningitis Among Febrile Infants Aged 28 Days or Younger. JAMA. Published online December 08, 2025.

Date: April 3, 2026

Dr. Margarita Ramos

Guest Skeptic: Dr. Margarita Ramos is a pediatric hospitalist at Children’s National Hospital in Washington, D.C., and Assistant Professor of Pediatrics at the George Washington University School of Medicine and Health Sciences where completed the Master Teacher Leadership Development Program in 2024. Her scholarly interests include equity in medical education and health services research.

Case: A 12-day-old boy is brought to the emergency department (ED) by his parents for fever. At home, he felt a little warm, so they took his temperature and found it was 38.3°C. The family called the boy’s pediatrician, who told them to bring him to the ED immediately. The baby has been feeding well. He has had a normal number of wet diapers and stools. He has no other medical history and was born full-term. On your exam, the baby looks good. There is no obvious source for his fever.

His parents say to you: “Our pediatrician told us that fevers at this age are worrisome, and our baby may need a lot of testing, including something called a lumbar puncture. We looked it up, and it sounds really scary. Do we have to do all that?”

Background:

We’re back on the topic of well-appearing febrile infants, and things have changed! Specifically, the “limbo” bar of age for which of the infants requiring a lumbar puncture (LP) has dropped quite a bit. Some may recall practicing at a time when any febrile babies ≤3-months-old were getting an LP. Later, that bar had dropped down to febrile babies ≤28 days getting an LP.

Along the way, we’ve had various tools to help guide us in identifying babies at low risk for what was once termed a serious bacterial infection (SBI), including urinary tract infection, bacteremia, and bacterial meningitis. These included tools like the Philadelphia, Rochester, and Boston criteria that risk-stratified based on pre-determined thresholds for temperature, lab tests, urine studies and more.

In 2019, the Pediatric Emergency Care Applied Research Network (PECARN) derived and validated a clinical decision rule for identifying low-risk febrile infants based on urine, absolute neutrophil count (ANC) and procalcitonin. We covered this study in SGEM#296.

The rounded PECARN Rule is:

  1. Negative urinalysis
  2. Absolute Neutrophil Count (ANC) ≤4,000/µL
  3. Serum procalcitonin ≤0.5 ng/ml

In 2021, we saw the limbo bar drop again with new guidance from the American Academy of Pediatrics (AAP) covered on SGEM#341. The age for LP moved down to 22 days. Based on this guideline, the decision to perform LP on infants from 22 to 28 days could be guided by inflammatory markers.

There was also another shift. Instead of focusing on SBIs, which included UTIs, one of the most common sources of infection, researchers started to focus on bacteremia and bacterial meningitis, termed invasive bacterial infections (IBIs), which have very bad consequences if missed.

Right now, the bar sits around 21–22 days because that’s where the data feels comfortable. And to be fair, newborns are different from older infants. Their immune systems are immature, their symptoms are subtle, and the consequences of missing meningitis are enormous. So naturally, we are cautious.

Clinical Question: How accurately can the PECARN rule identify febrile infants 28 days or younger at low risk for invasive bacterial infections?

Dr. Brett Burstein

Reference: Burstein B, et al. Prediction of Bacteremia and Bacterial Meningitis Among Febrile Infants Aged 28 Days or Younger. JAMA. Published online December 08, 2025.

  • Population: well-appearing febrile infants ≤ 28 days, temperature ≥38°C, from four prospective cohort studies across six countries within the global Pediatric Emergency Research Network (PERN) who underwent testing with PECARN rule components (procalcitonin, ANC, UA/urine dipstick).
    • Excluded: Criteria differed across the included studies. Some exclusion criteria included prematurity, pre-existing medical conditions, and being critically ill. Other studies excluded infants with viral signs.
  • Intervention: PECARN clinical decision rule
  • Comparison: None
  • Outcome: Diagnostic accuracy of the PECARN rule to identify infants with IBI (bacteremia or bacterial meningitis)
  • Type of Study: A pooled analysis of 5 published prospective cohort studies that was analyzed using meta-analytic methods to assess diagnostic accuracy

Guest Authors:

Dr. Nathan Kuppermann

Dr. Brett Burstein is a paediatric emergency medicine physician at Montreal Children’s Hospital and Associate Professor in the Department of Pediatrics at McGill University. His research focuses on the care of febrile young infants, emphasizing parental preferences, shared decision-making, and family-centered outcomes. 

Dr. Nathan Kuppermann is executive vice president, chief academic officer of Children’s National Hospital and director of the Children’s National Research Institute. He also serves as chair of the Department of Pediatrics and associate dean of Pediatric Academic Affairs at the George Washington University School of Medicine and Health Sciences. Dr. Kuppermann is a pediatric emergency medicine physician, clinical epidemiologist and leader in emergency medical services for children.

 

Authors’ Conclusions: “The updated PECARN rule had higher sensitivity but lower specificity for identifying febrile infants 28 days or younger with invasive bacterial infections, with no missed cases of bacterial meningitis. These results may support shared decision-making regarding selective vs routine use of lumbar puncture among infants classified as low risk.”

Quality Checklist for Systematic Review Diagnostic Studies

  1. The diagnostic question is clinically relevant with an established criterion standard. Yes
  2. The search for studies was detailed and exhaustive. No
  3. The methodological quality of primary studies were assessed for common forms of diagnostic research bias. Yes and No.
  4. The assessment of studies was reproducible. Yes
  5. There was low heterogeneity for estimates of sensitivity or specificity. No 
  6. The summary diagnostic accuracy is sufficiently precise to improve upon existing clinical decision-making models. Yes
  7. Funding of the Study: No industry funding was reported
  8. Conflicts of Interest: No major conflicts of interest were reported

Results: They included 1537 infants in the primary analysis, of whom 69 (4.5%) had IBI. The majority were male (~59%) and presented within 12 hours of fever onset. Not surprisingly, most (86.15%) were hospitalized. Approximately 41% of infants met PECARN low-risk criteria.

Of those infants who had invasive bacterial infections:

  • 58 with bacteremia
  • 11 with bacterial meningitis (0.7%)

The prevalence of IBI ranged from 2.5% to 7.3% between studies.

Key Results: The PECARN clinical prediction rule for identifying febrile infants ≤28 days at low risk for invasive bacterial infection has good sensitivity but low specificity. It did not miss any infants with bacterial meningitis.

The rule had a sensitivity of 94.2%, specificity of 41.6%, negative predictive value of 99.4%, and negative likelihood ratio of 0.14.

They also conducted a secondary analysis across all six cohorts (n=2531) that included the PECARN cohorts. The accuracy was quite similar.

All six cohorts together had 96 (3.8%) cases of IBI with 22 (0.9%) cases of bacterial meningitis.

The PECARN rule did misclassify 5 infants as low risk. Three infants had bacteremia with S. aureus, H. influenzae, and E. coli. The other two infants had positive urine cultures with E. coli, one of whom had concurrent E. coli bacteremia while the other had S. aureus bacteremia.

Tune into the podcast to hear Brett and Nate answer our questions!

Measurement of Temperature:

Here in the United States, we are more accustomed to measuring core temperature, especially in this very young population, rectally. It is mentioned that rectal temperature is used in three of the included cohort studies. But one study included temperatures measured by any method. There is differing evidence regarding the accuracy of temperature measurement by different methods.

How do you think the inclusion of that patient population may have affected your results?

Biases:

Some of the exclusion criteria may introduce selection bias. For example, in two of these study cohorts, patients were excluded because they had “viral signs present.” The AAP febrile infant guideline excludes infants with clinical bronchiolitis but states that infants with respiratory symptoms or positive viral test results may still be included.

What do you think about excluding babies with viral symptoms from the workup? How does the exclusion of those babies with viral signs in the two cohorts mentioned affect your results?

Here are some other examples of potential biases:

Not all infants in the pooled cohorts underwent a complete reference standard evaluation, particularly lumbar puncture for meningitis. This is appropriate given we try to limit invasive testing like LPs if possible. However, when only a subset of patients receives the gold-standard test, the accuracy of the diagnostic rule can be distorted. This is known as partial verification bias, where patients with higher clinical suspicion are more likely to undergo confirmatory testing. If infants classified as low risk were less likely to receive an LP, it is possible that some cases of meningitis could have been missed, artificially inflating the rule’s sensitivity (true positive) estimates.

The authors followed the STARD guidelines for diagnostic accuracy studies, but there was not a formal methodological quality assessment such as the QUADAS-2 of the included studies. (Note: Again, this study was not a SRMA). Structured tools such as QUADAS-2 evaluate bias across domains, including patient selection, index test application, reference standard, and patient flow. Without this systematic assessment, readers cannot easily determine whether individual studies were at high risk of bias.

Here is a paper on understanding the direction of bias in studies of diagnostic test accuracy. Kohn et al AEM 2013.

Aligning with the (AAP) Guidelines:

The AAP febrile infant guidelines, at this time still recommend LP for any febrile baby 21 days or under.

How do you advise clinicians to proceed at this time, given the discordance?

Are we ready to stop performing LPs on babies 0-28 days who are low risk? Is this ready for implementation or should we wait for more data?

Procalcitonin vs. No-calcitonin?

Lack of access to procalcitonin testing or a timely procalcitonin result is still a big limitation to the the application of this rule at many practice locations.

At this time, is there a substitute for procalcitonin that can be used with this rule, such as CRP, to avoid LP in these babies?

Disposition:

Those infants 0-28 days who do NOT meet low-risk criteria, nothing has changed: perform the full workup, including LP.

What about those who meet low risk by the PECARN criteria? Are they being sent home, admitted? Do they need empiric antibiotics?

Bonus Question: Impact of Vaccination:

All the cohort studies included in this meta-analysis were conducted between 2008 and 2024, during which there was widespread group B strep prophylaxis for pregnant women and Hib and pneumococcal conjugate vaccinations. In this age, we are seeing increasing vaccine hesitancy and the re-emergence of some vaccine-preventable illnesses.

Should this trend continue, how do you think this will impact the accuracy and use of the clinical decision rule?

 Comment on the Authors’ Conclusion Compared to the SGEM Conclusion: We agree with the authors’ conclusion.

SGEM Bottom Line: The PECARN rule appears highly sensitive for identifying invasive bacterial infection in well-appearing febrile neonates, given the modest specificity and methodological limitations of the pooled evidence, clinicians should use it as a decision support tool to inform shared decision-making rather than as a “rule” to eliminate clinical judgment.

Case Resolution: You tell the parents that at this age, it is often difficult to determine the exact source of the fever. You explain that the fever could be due to a virus, bacteria in the blood, bacteria in the urine, or bacteria in the spinal fluid. You start with urine and blood testing. The child meets PECARN low-risk criteria. You engage in shared-decision making around performing an LP and admit the baby to the hospital for observation.

Clinical Application:

We could lower the limbo bar and do fewer LPs  if we consider the risk tolerance of families and clinicians, rather than strict age cutoffs, to drive decisions.

Try to make the decisions with the family. We imagine most would be rather relieved that a fever in their newborn does not automatically equal getting an LP.

HSV still makes us nervous, particularly in this age group. The PECARN rule and similar tools are fantastic at identifying babies at low risk for bacterial meningitis. But HSV meningitis doesn’t necessarily present with the same findings (or fever alone).

Tune in to hear how Brett and Nate talk about challenges around implementation.

What Do I Tell My Patient/Family?

I’m sorry you and your baby are here. I can appreciate why you are worried. It is often difficult at this age to determine the exact source of the fever. The fever could be caused by a virus, but it could also be due to bacteria in the urine or blood. The last place we sometimes look is the spinal fluid, which coats the brain. This can cause something called meningitis. We can start by testing your baby’s urine and blood. Based on those results, we can discuss whether we should proceed with a lumbar puncture.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

Resources:

Canadian Paediatric Society Position Statement Management of Well-Appearing Febrile Young Infants

Intermountain Health Care Process For Assessment and Management of Febrile Infants 3-60 Days

SGEM Episodes

  • SGEM #171: Step-by-Step Approach to the Febrile Infant
  • SGEM#296: She’s Got the Fever but Does She Need an LP, Antibiotics or an Admission?
  • SGEM#341: Are the AAP Guidelines for the Evaluation and Management of the Well-Appearing Febrile Infant
  • SGEM#387: Lumbar Punctures in Febrile Infants with Positive Urinalysis
  • SGEM #474: Help! Which Clinical Decision Aid Should I Use to Risk Stratify Febrile Infants?
  • SGEM #501: Here It Goes Again- Another Clinical Decision Rule for Febrile Infants 61-90 Days