Last reviewed: March 2026Contents
MDM Templates
Febrile Neonate (0-28 Days)
Neonate presents with fever (rectal temp ≥38.0°C). Per AAP 2021 guidelines, all febrile infants ≤28 days require full sepsis evaluation including blood culture, catheterized urinalysis with culture, and lumbar puncture regardless of clinical appearance.[1]
Presentation not consistent with an obvious benign source that would change management. Neonates in this age group have immature immune systems and limited ability to localize infection — clinical appearance alone cannot reliably exclude serious bacterial infection.
Plan: Empiric parenteral antibiotics administered after cultures obtained. Admit for continued monitoring and culture results (minimum 24-36 hours for blood culture observation).
If HSV risk factors present (maternal history, vesicular rash, seizures, ill appearance, LFT abnormalities, CSF pleocytosis): Acyclovir 20 mg/kg IV added to empiric regimen.
Febrile Infant 29-60 Days — Low Risk
Infant 29-60 days old presents with fever (rectal temp ≥38.0°C). Well appearing with no chronic medical conditions, born at ≥37 weeks gestation, and no prior hospitalizations or antibiotics within 48 hours.
Inflammatory markers reassure against serious bacterial infection: urinalysis negative (WBC <10 per HPF, negative leukocyte esterase, negative nitrites), ANC <4000/µL, and procalcitonin <0.5 ng/mL.[1] All three low-risk criteria met per AAP 2021 guidelines.
Plan: Blood culture obtained. LP deferred given low-risk stratification. Discharge with close follow-up within 24 hours and reliable caretaker who understands return precautions. Return precautions for fever persistence, poor feeding, irritability, lethargy, rash, or any change in behavior.
If UTI identified (positive UA, culture pending): Empiric antibiotics started for UTI. Discharge with oral antibiotics and follow-up within 24 hours for culture result. LP not required if UTI is the clear source and infant meets all other low-risk criteria.[1]
Febrile Infant 29-60 Days — Not Low Risk
Infant 29-60 days old presents with fever (rectal temp ≥38.0°C). Does not meet all AAP low-risk criteria — specifically: ***.
Given failure to meet low-risk stratification, this infant requires expanded evaluation and parenteral antibiotics pending culture results.[1]
Plan: Blood culture, catheterized UA with culture, and lumbar puncture performed. Empiric parenteral antibiotics administered after cultures obtained. Admit for ongoing monitoring and culture observation.
If ill appearing at any age: Full sepsis evaluation and empiric antibiotics regardless of inflammatory markers. Consider ICU-level care. HSV evaluation if any concerning features.
Clinical Education
AAP 2021 Guidelines Overview
The AAP 2021 Clinical Practice Guideline is a paradigm shift for febrile infants. It replaces the older Rochester, Philadelphia, and Boston criteria with a unified, evidence-based, age-stratified approach. The key innovation is the formal incorporation of inflammatory biomarkers — specifically procalcitonin and ANC — alongside urinalysis to risk-stratify infants 29-60 days old.[1]
What changed: Well-appearing febrile infants 29-60 days who meet all low-risk criteria (negative UA, ANC <4000, PCT <0.5) can now be managed without LP and without empiric antibiotics, with discharge and close follow-up. This was previously unthinkable — the old approach required LP and admission for nearly all febrile infants under 60 days.
What didn’t change: All febrile neonates ≤28 days still get the full workup (blood culture, UA, LP) and empiric antibiotics regardless of appearance. The guidelines also explicitly apply only to well-appearing, full-term infants without comorbidities.
Age-Based Stratification
| Age | Workup | LP? | Antibiotics? | Disposition |
| 8-21 days | Blood Cx, UA/Cx, LP | Yes — always | Yes — always | Admit |
| 22-28 days | Blood Cx, UA/Cx, inflammatory markers. LP if any marker abnormal. | If not low-risk | Yes — always (even if low-risk, give parenteral dose and admit) | Admit (even if low-risk per AAP) |
| 29-60 days | Blood Cx, UA/Cx, inflammatory markers | If not low-risk | Only if not low-risk (or UTI identified) | Low-risk: can discharge with 24h follow-up. Not low-risk: admit. |
Note on 22-28 days: The AAP guideline technically allows 22-28 day infants who meet low-risk criteria to avoid LP, but still recommends parenteral antibiotics and hospital admission for this age group. In practice, many institutions still perform LP on all infants ≤28 days — this is a reasonable and defensible approach.[1]
Inflammatory Markers: ANC, PCT, UA
All three must be normal to classify an infant 29-60 days as low-risk. If any single marker is abnormal, the infant is not low-risk and requires LP and parenteral antibiotics.[1]
| Marker | Low-Risk Cutoff | Notes |
| Urinalysis | WBC <10/HPF, LE negative, nitrites negative | Must be catheterized specimen. Bag specimens are unreliable in this age group. |
| ANC | <4,000/µL | ANC outperforms total WBC for predicting invasive bacterial infection in this age group.[2] |
| Procalcitonin | <0.5 ng/mL | PCT is the single best biomarker for invasive bacterial infection in febrile infants. Physiologic surge in first 48-72 hours of life limits utility in the youngest neonates.[3] |
WBC is no longer the primary marker. The AAP 2021 guidelines deliberately moved away from total WBC count (the old 5-15k range) and replaced it with ANC, which has better sensitivity and specificity for serious bacterial infection in this population.[1]
If your institution doesn’t have procalcitonin: This is a real barrier. Without PCT, you cannot fully apply the AAP low-risk criteria. Many experts recommend treating these infants as not-low-risk (LP + antibiotics + admission) if PCT is unavailable. Advocate for PCT availability in your ED.
When to LP
LP is required for all febrile infants ≤21 days regardless of appearance. For 22-28 days, LP is required if any inflammatory marker is abnormal. For 29-60 days, LP is required if any inflammatory marker is abnormal.[1]
LP can be deferred in well-appearing 29-60 day infants who meet all three low-risk criteria (normal UA, ANC <4000, PCT <0.5). This is one of the most practice-changing elements of the 2021 guidelines — previously almost all febrile infants under 60 days got an LP.
Do not let a failed LP change your management. If you attempt LP and get a traumatic tap or dry tap, the infant should still receive antibiotics if indicated. A failed LP is not a reason to withhold treatment. It is a reason to admit for observation and consider repeating the LP when feasible.
CSF interpretation pearls: Normal neonatal CSF has higher WBC and protein than older children. A reasonable upper limit for normal CSF WBC in neonates is ~20/µL (some references use 15). Protein can be up to 150 mg/dL in the first week of life. Always send CSF culture — cell counts alone cannot rule out meningitis.[4]
Empiric Antibiotics by Age
| Age | Regimen | Rationale |
| 0-28 days | Ampicillin 50 mg/kg IV + Gentamicin 4-5 mg/kg IV | Covers GBS, E. coli, Listeria. Ampicillin provides Listeria and Enterococcus coverage that cephalosporins miss. |
| 29-60 days | Ceftriaxone 50 mg/kg IV/IM | Covers most common pathogens (GBS, E. coli, S. pneumoniae). Listeria risk drops significantly after 28 days. Add ampicillin if Listeria concern persists. |
| UTI source (29-60d, low-risk) | Ceftriaxone 50 mg/kg IM × 1, then oral cephalosporin | If discharged with UTI, give parenteral dose in ED, start oral antibiotics, and ensure 24-hour follow-up with culture check. |
Cefotaxime is no longer available. The manufacturer discontinued it. Ceftriaxone is now the standard third-generation cephalosporin for infants >28 days. For neonates ≤28 days, avoid ceftriaxone (risk of bilirubin displacement and biliary sludge) — use gentamicin or cefepime as the gram-negative agent alongside ampicillin.[5]
Gram-negative CSF gram stain: If CSF gram stain shows gram-negative organisms, consult infectious disease immediately. Consider broadening to meropenem given increasing ESBL prevalence in neonatal gram-negative meningitis.
HSV Considerations
HSV meningitis/encephalitis is the diagnosis you cannot afford to miss in a febrile neonate. Mortality without treatment is >80% for disseminated disease, and even with treatment, neurologic outcomes are devastating if diagnosis is delayed.[6]
Add acyclovir 20 mg/kg IV if any of the following are present: maternal history of genital HSV (especially primary infection near delivery), vesicular skin lesions on the infant, seizures, ill or toxic appearance, elevated LFTs/transaminases, CSF pleocytosis with negative gram stain, or thrombocytopenia.
The diagnostic challenge: HSV can present identically to bacterial sepsis in the first 2-3 weeks of life. Only ~40% of neonatal HSV presents with the classic vesicular rash. Many cases present with nonspecific fever, irritability, and poor feeding. Maternal HSV history is absent in the majority of cases — about 75% of mothers of infants with neonatal HSV have no known history of herpes.[6]
Low threshold in the first 21 days of life. Most neonatal HSV presents between days 3-21. After 28 days, HSV becomes far less likely as a cause of fever. If acyclovir is started, send HSV PCR of CSF and surface cultures (mouth, nasopharynx, conjunctivae, rectum).
The Bronchiolitis Exception
Febrile infants 29-60 days with clear bronchiolitis are a special case. Multiple studies have shown that the risk of serious bacterial infection (other than UTI) is significantly lower in febrile infants with a positive RSV or viral respiratory panel and clinical bronchiolitis.[7]
The AAP guideline does not explicitly create a separate pathway for bronchiolitis, but many institutions and experts recommend the following approach for well-appearing 29-60 day infants with clear viral bronchiolitis: obtain blood culture and catheterized UA (UTI can coexist with bronchiolitis), defer LP if inflammatory markers are low-risk, and admit for respiratory monitoring without empiric antibiotics unless inflammatory markers are concerning.
UTI must still be evaluated. The rate of concurrent UTI in febrile infants with bronchiolitis is approximately 5-7% — not low enough to skip the UA. The risk of bacteremia and meningitis, however, drops to <1% with a confirmed viral source.[7]
Disposition Criteria
Discharge (29-60 days, low-risk only): All three inflammatory markers normal (UA, ANC, PCT). Well-appearing. No chronic medical conditions. Full-term birth. Reliable caretaker present who verbalizes understanding of return precautions. Follow-up confirmed within 24 hours. Blood culture obtained prior to discharge.[1]
Admit: All infants ≤28 days regardless of appearance or labs. All 29-60 day infants who do not meet low-risk criteria. All ill-appearing infants at any age. Any infant with positive CSF findings or abnormal inflammatory markers. Any infant whose caretaker is unable to ensure 24-hour follow-up or does not have reliable transportation to return if clinical change occurs.
The blood culture callback plan is critical. If discharging a low-risk 29-60 day infant, there must be a system to ensure blood culture results are checked at 24 and 48 hours. If the culture turns positive, the infant must be immediately recalled for evaluation and admission. This callback plan should be documented and communicated to the family.
Fussy Infant MDM
No evidence of strep pharyngitis at this time.
No evidence of torsion.
Patient without diarrhea or concerning pulmonary exam findings.
Given history and exam, no overt evidence of emergent intra-abdominal process, corneal abrasion or tourniquets causing fussiness
Plan discharge home.
- Colic
- Possible colic; discussed use of soothing activities, feeding more frequently, use of pacifier.
- Definition of colic: Crying for ≥3hr/day for ≥3 days/week per week over a 3-week period in an infant <4months old.
References
- Pantell RH, Roberts KB, Adams WG, et al. Evaluation and management of well-appearing febrile infants 8 to 60 days old. Pediatrics. 2021;148(2):e2021052228. PubMed
- Kuppermann N, Dayan PS, Levine DA, et al. 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
- Milcent K, Faesch S, Gras-Le Guen C, et al. Use of procalcitonin assays to predict serious bacterial infection in young febrile infants. JAMA Pediatr. 2016;170(1):62-69. PubMed
- Kestenbaum LA, Ebberson J, Zorc JJ, et al. Defining cerebrospinal fluid white blood cell count reference values in neonates and young infants. Pediatrics. 2010;125(2):257-264. PubMed
- Bradley JS, Wassel RT, Lee L, Nambiar S. Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events. Pediatrics. 2009;123(4):e609-e613. PubMed
- Kimberlin DW, Lin CY, Jacobs RF, et al. Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections. Pediatrics. 2001;108(2):230-238. PubMed
- Ralston SL, Lieberthal AS, Meissner HC, et al. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014;134(5):e1474-e1502. PubMed
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