⚠️ Clinical Disclaimer: CA FIRST is based on AAP CPG 2021 + Roseville Protocol. For well-appearing, previously healthy, full-term infants only. Clinical judgment required. Ill-appearing infants require full sepsis workup regardless of age — this algorithm does not apply.
✅ Automatic Low Risk (regardless of age 22–90 days):
Bronchiolitis (with or without RSV positive) — no cases of IBI reported in RSV+ infants 22–90 days in CA FIRST data (n=235). · Fever within 48 hours of routine immunization — no cases of IBI in 221 infants. These infants may be managed with reduced workup after clinical assessment.
🧫 HSV Risk — Consider acyclovir if ANY present:
Maternal genital HSV lesions or fever 48h before/after delivery · Vesicles · Seizures · Hypothermia · Mucous membrane ulcers · CSF pleocytosis without + Gram stain · Leukopenia · Thrombocytopenia · Elevated ALT
HSV workup: CSF PCR · Surface swabs (mouth, NP, conjunctivae, anus) · ALT · Blood PCR · Acyclovir 20 mg/kg IV q8h
HSV workup: CSF PCR · Surface swabs (mouth, NP, conjunctivae, anus) · ALT · Blood PCR · Acyclovir 20 mg/kg IV q8h
7–21 Days — All Require Full Workup
🔴 ALL febrile infants 7–21 days = HIGH RISK — No stratification
All infants in this age group are high risk regardless of inflammatory markers. Full sepsis workup, parenteral antibiotics, and hospital admission are required. Inflammatory marker results may guide ongoing decisions but do not change initial management.
🔬 Required Workup
1
Blood: CBC with differential, blood culture, CMP
2
Urine: UA by catheter + urine culture
3
CSF: Cell count, Gram stain, glucose, protein, bacterial culture, enterovirus PCR (if available or enterovirus season)
4
Inflammatory markers: Procalcitonin (if available), CRP, ANC
5
HSV: Evaluate risk factors — see callout above
6
Respiratory: Chest X-ray if respiratory symptoms; RSV/flu/COVID testing as appropriate
💊 Treatment & Disposition
A
Ampicillin 50 mg/kg IV q6–8h (Listeria, GBS, enterococcus coverage)
B
Gentamicin 4 mg/kg IV q24h OR Cefotaxime 50 mg/kg IV q8h (if gentamicin unavailable)
C
If CSF pleocytosis or HSV concern: Add Acyclovir 20 mg/kg IV q8h
D
Admit to hospital — all infants 7–21 days regardless of IM results
⚠️ Do NOT use ceftriaxone in first 28 days (bilirubin displacement risk)
📊 Inflammatory Marker Reference (7–21 days)
| Marker | Abnormal Threshold | Notes |
|---|---|---|
| Procalcitonin (PCT) | > 0.5 ng/mL | Preferred if rapid turnaround available |
| CRP | > 20 mg/L | May lag 12–24h early in illness |
| ANC | > 4000–5200/mm³ | Cutoff varies by protocol; 5200 = PECARN |
| WBC | < 5000 or > 15,000 | Less specific than ANC alone |
Note: Elevated IMs in 7–21 day group guide ongoing decisions but do NOT change initial management — all require full workup + admission.
22–28 Days — Transitional Risk Stratification
🟡 Transitional Zone — IMs can guide LP decision, not admission
Risk of meningitis is lower in 22–28 day group than <22 days. In some circumstances, clinicians may elect to defer LP and initiate antibiotics — recognizing this limitation. Hospital admission still strongly recommended for most in this age group.
🔬 Required Workup
1
Blood: CBC with diff, blood culture, CMP, PCT (if available), CRP
2
Urine: UA by catheter + urine culture
3
CSF: Strongly recommended — may defer if IMs all normal AND clinical gestalt low risk (shared decision-making)
4
HSV: Evaluate risk factors — risk lower after 28 days but still consider if clinical features present
5
Respiratory: CXR if respiratory symptoms; viral testing as appropriate
📊 IM Results → Management
ANY IM Abnormal
Full workup including LP · Ampicillin + gentamicin/cefotaxime · Admit · Consider acyclovir if HSV risk
All IMs Normal — LP Deferred
Options: Observe without treatment + close follow-up · OR empiric antibiotics + admit · Shared decision-making with family · Must reevaluate in 24h
All IMs Normal — LP Obtained + Normal CSF
Lower threshold to discharge with close 24h follow-up if well-appearing and reliable family
⚠️ Do NOT use ceftriaxone in first 28 days (bilirubin displacement)
📊 Inflammatory Marker Thresholds (22–28 days)
| Marker | Abnormal | Interpretation |
|---|---|---|
| PCT | > 0.5 ng/mL | Best single marker if rapid turnaround available |
| CRP | > 20 mg/L | Use with ANC if PCT unavailable |
| ANC | > 4000/mm³ (AAP) or > 5200/mm³ (PECARN) | Combined with CRP improves specificity |
| Temp | > 38.5°C | Use as IM equivalent if PCT unavailable |
29–60 Days — Risk Stratification by Inflammatory Markers
🔴 HIGH RISK — Any IM Abnormal
Workup:
1
CBC, blood culture, CMP, PCT, CRP
2
UA by catheter + urine culture
3
LP: CSF cell count, culture, Gram stain, glucose, protein, enterovirus PCR
4
CXR if respiratory symptoms
Treatment:
A
Ceftriaxone 50 mg/kg IV q24h (safe after 28 days)
B
Consider ampicillin if Listeria concern (rare)
C
Admit to hospital
🟢 LOW RISK — All IMs Normal
Workup:
1
CBC, blood culture, PCT, CRP
2
UA by catheter + urine culture
3
LP: Not required if all IMs normal and well-appearing
4
CXR only if respiratory symptoms
Disposition:
A
No antibiotics required
B
Discharge home if reliable family + reliable phone + transportation
C
Mandatory 24h reevaluation (ED or PCP)
D
Hospital observation is always an acceptable alternative
📊 Inflammatory Marker Thresholds (29–60 days)
| Marker | Abnormal | Notes |
|---|---|---|
| PCT | > 0.5 ng/mL | Preferred — use PECARN rule if available (PCT + ANC) |
| CRP | > 20 mg/L | Use with ANC when PCT unavailable (Step-by-Step) |
| ANC | > 4000/mm³ (AAP) or > 5200/mm³ (PECARN) | — |
| UA | + LE, nitrites, or pyuria | Abnormal UA = high risk regardless of other IMs |
| Temp | > 38.5°C | Use as IM surrogate when PCT not available |
If PCT unavailable: Use CRP + ANC + temperature (>38.5°C counts as elevated IM). Any single abnormal = high risk.
🏠 Discharge Criteria (29–60 days, Low Risk)
All of the following must be met to discharge:
Well-appearing
All IMs normal
UA normal
Reliable caregiver
Phone + transportation available
Agrees to 24h f/u
Blood cx sent before discharge
Return precautions: worsening fever, poor feeding, color change, decreased activity, any parental concern
61–90 Days — CA FIRST Extended Guidance
🟡 61–90 Days — CA FIRST Extended (not in AAP CPG)
The AAP 2021 CPG addresses only 8–60 days. CA FIRST extended the algorithm to 90 days using Kaiser Northern California ED data. Lower overall IBI risk in this age group. Most can be risk-stratified and managed as outpatients if low risk.
🔴 HIGH RISK (61–90 days)
Any of the following:
Abnormal UA
ANC > 5200/mm³
PCT > 0.5 ng/mL
CRP > 20 mg/L
Temp > 38.5°C + any abnormal IM
A
Full workup: blood cx, UA/ucx, CBC, CMP, IMs
B
LP at clinician discretion — lower meningitis risk at this age
C
Ceftriaxone 50 mg/kg IV/IM
D
Admit or observation depending on clinical trajectory
🟢 LOW RISK (61–90 days)
All of the following:
Well-appearing
Normal UA
All IMs normal
A
Blood culture + UA at minimum
B
LP generally not required
C
Discharge home without antibiotics
D
Reliable 24h follow-up required
E
Clear return precautions
✅ Special Low-Risk Groups (61–90 days):
Bronchiolitis (RSV+ or clinical) — no IBI cases in CA FIRST data for this age group with RSV. · Post-immunization fever (within 48h) — no IBI cases in 221 infants. · These infants may be managed conservatively with clinical assessment and reliable follow-up.
Quick Reference — IBI Risk by Age
7–21 days
IBI risk: ~8–12%
Meningitis risk: ~3–4%
LP: Required
Admit: Always
Meningitis risk: ~3–4%
LP: Required
Admit: Always
22–60 days
IBI risk: ~2–4%
Meningitis risk: ~0.5–1%
LP: Based on IMs
Admit: If high risk
Meningitis risk: ~0.5–1%
LP: Based on IMs
Admit: If high risk
61–90 days
IBI risk: ~1–2%
Meningitis risk: <0.5%
LP: Generally not needed
Admit: Low risk if IMs normal
Meningitis risk: <0.5%
LP: Generally not needed
Admit: Low risk if IMs normal
📖 Source & References
CA FIRST: Greenhow TL et al. Perm J. 2023;27(3):92–98. doi:10.7812/TPP/23.030 · Kaiser Permanente Northern California ED data, n=3527 infants 7–90 days (2010–2019)
AAP CPG: Pantell RH et al. Pediatrics. 2021;148(2):e2021052228 · PECARN prediction rule: Kuppermann N et al.
UCSF NorCal Consortium Febrile Infant Guidelines 2022
AAP CPG: Pantell RH et al. Pediatrics. 2021;148(2):e2021052228 · PECARN prediction rule: Kuppermann N et al.
UCSF NorCal Consortium Febrile Infant Guidelines 2022