This episode of EM Pulse dives into one of the most stressful scenarios in the ED: the febrile infant in the first month of life. Traditionally, a fever in this age group has meant an automatic “full septic workup,” including the dreaded lumbar puncture (LP).

But times are changing. We sit down with experts Dr. Nate Kuppermann and Dr. Brett Burstein to discuss a landmark JAMA study that suggests we might finally be able to safely skip the LP in many of our tiniest patients.

The Study: A Game Changer for Neonates

Our discussion centers on a massive international pooled study evaluating the PECARN Febrile Infant Rule specifically in infants aged 0–28 days. While previous guidelines were conservative due to a lack of data for this specific age bracket, this study provides the evidence we’ve been waiting for.

The Cohort: A large pool of infants across multiple countries.
The Findings: The PECARN rule demonstrated an exceptionally high negative predictive value for invasive bacterial infections.
The Big Win: The rule missed zero cases of bacterial meningitis.

Defining the Danger: SBI vs. IBI

The experts break down why we are shifting our terminology and our clinical focus.

Serious Bacterial Infection (SBI)

Historically, this was a “catch-all” term including Urinary Tract Infections (UTIs), bacteremia, and meningitis. However, UTIs are generally more common, easily identified via urinalysis, and typically less life-threatening than the other two.

Invasive Bacterial Infection (IBI)

This term refers specifically to bacteremia and bacterial meningitis. These are the “high-stakes” infections the PECARN rule is designed to rule out. Dr. Kuppermann notes that we should ideally view bacteremia and meningitis as distinct entities, as the clinical implications of a missed meningitis case are far more severe.

The HSV Elephant in the Room

One of the primary reasons clinicians hesitate to skip an LP in a neonate is the fear of missing Herpes Simplex Virus (HSV) infection.

Low Baseline Risk: While the overall risk of HSV in a febrile infant is low, the risk of “isolated” HSV (meningitis without other signs or symptoms) is even rarer.
Screening Tools: Most infants with HSV appear clinically ill. Clinicians can also use ALT (liver function) testing as a secondary screen – transaminase elevation is a common marker for systemic HSV.
Clinical Judgment: If the baby is well-appearing, has no maternal history of HSV, no vesicles, and no seizures, the risk of missing HSV by skipping the LP is exceptionally low.

Practical Application: Shared Decision-Making

This isn’t just about the numbers—it’s about the parents.

“Families don’t mind their babies being admitted… They do not want the lumbar puncture. It is the single most anxiety-provoking aspect of care.” — Dr. Brett Burstein

The PECARN “Low-Risk” Criteria:

(Remember, this rule applies only to infants who are not ill-appearing.)

Urinalysis: Negative
Absolute Neutrophil Count (ANC): ≤ 4,000/mm³
Procalcitonin (PCT): ≤ 0.5 ng/mL

The Bottom Line: If an infant is well-appearing and meets these criteria, physicians can have a nuanced conversation with parents about the risks and benefits of forgoing the LP, while still admitting the child for observation (often without empiric antibiotics) while cultures brew.

Key Takeaways

The “Well-Appearing” Filter: If an infant looks ill, the rule does not apply. These patients require a full workup, including an LP, regardless of lab results.
Meticulous Physical Exam: Assess for a strong suck, normal muscle tone, brisk capillary refill, and any rashes or vesicles.
History is Key: Always ask about maternal GBS/HSV status, pregnancy or birth complications, prematurity, sick contacts, and any changes in feeding, stooling or activity.
Procalcitonin: PCT is the superior inflammatory marker for this rule. If your facility only offers traditional markers like CRP, the PECARN negative predictive value cannot be strictly applied. In the words of Dr. Kuppermann: “If you don’t have it, for God’s sakes, just get it!
ALT to Screen for HSV: While not part of the official PECARN rule, our experts suggest that significantly elevated liver enzymes should raise suspicion for systemic HSV.
Observe, Don’t Discharge: Being “low risk” does not mean the infant goes home. All infants ≤ 28 days still require admission for 24-hour observation and blood/urine cultures.

We want to hear from you! Does this change how you approach febrile neonates in the ED? How do you handle shared decision-making with parents? Connect with us on social media @empulsepodcast or on our website ucdavisem.com.

Hosts:

Dr. Julia Magaña, Professor of Pediatric Emergency Medicine at UC Davis

Dr. Sarah Medeiros, Professor of Emergency Medicine at UC Davis

Guests:

Dr. Nate Kuppermann, Executive Vice President and Chief Academic Officer; Director, Children’s National Research Institute; Department Chair, Pediatrics, George Washington University School of Medicine and Health Sciences

Dr. Brett Burstein, Clinician-Scientist and Pediatric Emergency Medicine Physician at Montreal Children’s Hospital, McGill University

Resources:

Burstein B, Waterfield T, Umana E, Xie J, Kuppermann N. Prediction of Bacteremia and Bacterial Meningitis Among Febrile Infants Aged 28 Days or Younger. JAMA. 2026 Feb 3;335(5):425-433. doi: 10.1001/jama.2025.21454. PMID: 41359314; PMCID: PMC12687207

“Hot” Off the Press: Infant Fever Rule

Do I really need to LP a febrile infant with a UTI?

PECARN Infant Fever Update: 61-90 Days

Kuppermann N, Dayan PS, Levine DA, Vitale M, Tzimenatos L, Tunik MG, Saunders M, Ruddy RM, Roosevelt G, Rogers AJ, Powell EC, Nigrovic LE, Muenzer J, Linakis JG, Grisanti K, Jaffe DM, Hoyle JD Jr, Greenberg R, Gattu R, Cruz AT, Crain EF, Cohen DM, Brayer A, Borgialli D, Bonsu B, Browne L, Blumberg S, Bennett JE, Atabaki SM, Anders J, Alpern ER, Miller B, Casper TC, Dean JM, Ramilo O, Mahajan P; 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 Apr 1;173(4):342-351. doi: 10.1001/jamapediatrics.2018.5501. PMID: 30776077; PMCID: PMC6450281.

Pantell RH, Roberts KB, Adams WG, Dreyer BP, Kuppermann N, O’Leary ST, Okechukwu K, Woods CR Jr; SUBCOMMITTEE ON FEBRILE INFANTS. Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old. Pediatrics. 2021 Aug;148(2):e2021052228. doi: 10.1542/peds.2021-052228. Epub 2021 Jul 19. Erratum in: Pediatrics. 2021 Nov;148(5):e2021054063. doi: 10.1542/peds.2021-054063. PMID: 34281996.

****Thank you to the UC Davis Department of Emergency Medicine for supporting this podcast and to Orlando Magaña at OM Productions for audio production services.