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neonatal.early-onset-sepsis.v1

Neonatal Early-Onset Sepsis (EOS)

pediatricsacuteneonatalpediatric
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Frame by gestational age cohort (≥35 0/7 wk term per Puopolo 30455342 vs ≤34 6/7 wk preterm per Puopolo 30455344), postnatal age in hours (EOS < 72 h), and birth weight (per-kg dosing).

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Cohort + age + weight captured; framework selected

Patient inputs (20)

Tachycardia or bradycardia — both seen in neonatal sepsis; bradycardia + apnea is high-acuity

Tachypnea / grunting / apnea — respiratory pattern drives ventilation decisions

Pre-/post-ductal SpO₂ gradient suggests PPHN coinfection; differential includes CHD

GBS-positive with inadequate IAP is a Kaiser EOS calculator high-weight factor (Verani CDC 2010 PMID 21088663)

Maternal fever ≥ 38°C OR clinical chorioamnionitis is the dominant Puopolo risk driver

ROM > 18 h is a classic risk factor; included in Kaiser EOS calculator weighting

Term ≥35 0/7 wk (Puopolo 30455342) vs preterm ≤34 6/7 wk (Puopolo 30455344) drive separate risk frameworks and drug-interval bands

Per-kg dosing for every antibiotic; VLBW < 1500 g cohort has higher EOS incidence and longer empiric-duration thresholds

EOS by definition is < 72 h; postnatal age also drives dosing-interval bands (week-1 vs > week 1 ampicillin q12h vs q8h)

WBC < 5K or > 25K, neutropenia, immature-to-total neutrophil ratio > 0.2 support EOS — Puopolo 2018

Minimum 1 mL per bottle; positive at 36-48 h is the LR+ > 100 anchor for EOS diagnosis (Schelonka)

CRP at 24 + 48 h pair has higher NPV than a single early value; rising CRP supports continuation of antibiotics

Hypoglycemia is a common sepsis comorbid; concurrent hyperglycemia suggests stress / steroids

Pneumonia infiltrate vs RDS pattern vs effusion — guides ventilation + differential

Hypothermia ≥ fever as EOS marker in neonate; temperature instability is a Puopolo 2018 clinical-status driver

Hypotension by gestational-age threshold drives vasoactive escalation

Active maternal genital HSV at delivery triggers acyclovir empirical coverage

Seizures + bulging fontanelle + meningismus → LP + meningitic-dose antibiotics (Puopolo 2018)

LP if culture-positive sepsis, CNS features, or persistent positive blood cultures — informs duration + meningitic dosing (Puopolo 2018)

Lactate > 4 mmol/L suggests perfusion failure; serial trend tracks resuscitation response

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No severity triggers declared for this engine.

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Recommended regimen

Neonatal EOS — empiric ampicillin + gentamicin; escalate per pathogen / clinical course (Puopolo 2018 PMID 30455342 / 30455344; Verani CDC 2010 PMID 21088663)
axis: eos_empiric_then_pathogen_directed
Selected axis "Neonatal EOS — empiric ampicillin + gentamicin; escalate per pathogen / clinical course (Puopolo 2018 PMID 30455342 / 30455344; Verani CDC 2010 PMID 21088663)" by default fallback (first axis)
  • ampicillin
    first line
    aminopenicillin
    ampicillin 50 mg/kg IV q8h (term, week 1) / q12h (preterm <34 wks PMA, week 1); meningitis dose 75-100 mg/kg/dose q6-8h • IV • q6-12h per GA + PMA band (max: max 200 mg/kg/day non-meningitic; 400 mg/kg/day meningitic)
    triggers: eos_empiric_recognition
    Covers GBS, Listeria, susceptible E. coli; standard EOS empiric backbone (Neofax 2024; Puopolo 2018; AAP Red Book 2024-2027 ch. neonatal sepsis)
    rxcui 733
  • gentamicin
    first line
    aminoglycoside
    gentamicin 4 mg/kg IV q24h (term) / 4.5 mg/kg q36h (late-preterm 30-34 wks GA) / 5 mg/kg q48h (preterm <30 wks GA, week 1) • IV • q24-48h extended interval (max: max 5 mg/kg/dose; trough <2 mcg/mL before 3rd dose)
    triggers: eos_empiric_recognition, gram_negative_synergy_with_ampicillin
    Gram-negative synergy with ampicillin; extended-interval dosing per Neofax 2024 + Puopolo 2018; trough <2 mcg/mL avoids nephro/ototoxicity. Lactation: minimal transfer; compatible (Neofax 2024)
    rxcui 1596450
  • acyclovir
    add on
    nucleoside_antiviral
    acyclovir 20 mg/kg IV q8h (term, week 1+); preterm <30 wks PMA: 20 mg/kg q12h • IV • q8-12h per GA + PMA (max: max 60 mg/kg/day; hold for AKI per Cr trend)
    triggers: active_maternal_genital_hsv_at_delivery, infant_vesicular_rash_or_csf_pleocytosis, unexplained_hepatitis_or_seizures
    Empiric HSV cover when maternal HSV at delivery, infant vesicular rash, unexplained hepatitis, or CSF pleocytosis; AAP Red Book 2024-2027 ch. HSV neonatal
    rxcui 281
  • pathogen_directed_definitive_antibiotics
    first line
    targeted_antimicrobial_per_culture
    Per organism + susceptibilities at 36-72 h culture-finalisation; narrow ampicillin alone for GBS; cefotaxime for E. coli meningitis (AVOID ceftriaxone <28 d) • IV • per pathogen
    triggers: culture_positive_with_speciation_and_susceptibility
    Stewardship and pathogen-directed narrowing per Puopolo 2018 + IDSA principles; ceftriaxone-avoid-<28-d is hard safety rule (bilirubin displacement + Ca-IVF incompatibility)

ed playbook — drug actions (3)

  1. 1. ampicillin 50 mg/kg IV
    rxcui 733
    50 mg/kg • IV • q8h (term, week 1) / q12h (preterm <34 wks PMA)
    trigger: EOS suspicion within 60 min
    Empiric Gram-positive + Listeria coverage; Neofax 2024 + Puopolo 2018
  2. 2. gentamicin 4 mg/kg IV
    rxcui 1596450
    4 mg/kg (term) / 5 mg/kg (preterm <30 wks) • IV • q24-48h extended interval
    trigger: EOS suspicion within 60 min
    Gram-negative synergy; trough monitoring before 3rd dose (Neofax 2024)
  3. 3. acyclovir 20 mg/kg IV
    rxcui 281
    20 mg/kg • IV • q8h (term) / q12h (preterm <30 wks PMA)
    trigger: Active maternal HSV at delivery OR infant vesicular rash OR unexplained hepatitis / seizures
    Empiric HSV cover (AAP Red Book 2024-2027 ch. HSV neonatal)

Auto-drafted A&P note

ed

Subjective

- Possible entry pathways: Neonate ≤72 h of life with tachypnea, grunting, retractions, or apnea — sepsis must be considered (Puopolo 2018 PMID 30455342); Neonate with temperature instability (hypothermia more common than fever in EOS) (Puopolo 2018 PMID 30455342); Lethargy, poor feeding, hypotonia — non-specific but high-yield EOS triggers (Puopolo 2018 PMID 30455342).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Neonatal Early-Onset Sepsis (EOS)** (neonatal.early-onset-sepsis.v1).
Phenotype framing: EOS vs RDS (no maternal sepsis risk factors; classic preterm ground-glass CXR — route to neonatal.respiratory-distress-syndrome.v1). EOS vs PPHN (pre-/post-ductal gradient; echo). EOS vs CHD (congenital cyanotic vs ductal-dependent — echo + hyperoxia test). EOS vs HIE (history of asphyxia / acidosis — route to neonatal.hypoxic-ischemic-encephalopathy.v1). EOS vs metabolic (inborn errors with shock-like presentation — acidosis + hyperammonemia + lactate).
Scope: Frame by gestational age cohort (≥35 0/7 wk term per Puopolo 30455342 vs ≤34 6/7 wk preterm per Puopolo 30455344), postnatal age in hours (EOS < 72 h), and birth weight (per-kg dosing).

Plan

Regimen axis: **Neonatal EOS — empiric ampicillin + gentamicin; escalate per pathogen / clinical course (Puopolo 2018 PMID 30455342 / 30455344; Verani CDC 2010 PMID 21088663)**.
1. ampicillin ampicillin 50 mg/kg IV q8h (term, week 1) / q12h (preterm <34 wks PMA, week 1); meningitis dose 75-100 mg/kg/dose q6-8h IV q6-12h per GA + PMA band (aminopenicillin, first line) — Covers GBS, Listeria, susceptible E. coli; standard EOS empiric backbone (Neofax 2024; Puopolo 2018; AAP Red Book 2024-2027 ch. neonatal sepsis)
2. gentamicin gentamicin 4 mg/kg IV q24h (term) / 4.5 mg/kg q36h (late-preterm 30-34 wks GA) / 5 mg/kg q48h (preterm <30 wks GA, week 1) IV q24-48h extended interval (aminoglycoside, first line) — Gram-negative synergy with ampicillin; extended-interval dosing per Neofax 2024 + Puopolo 2018; trough <2 mcg/mL avoids nephro/ototoxicity. Lactation: minimal transfer; compatible (Neofax 2024)
3. acyclovir acyclovir 20 mg/kg IV q8h (term, week 1+); preterm <30 wks PMA: 20 mg/kg q12h IV q8-12h per GA + PMA (nucleoside_antiviral, add on) — Empiric HSV cover when maternal HSV at delivery, infant vesicular rash, unexplained hepatitis, or CSF pleocytosis; AAP Red Book 2024-2027 ch. HSV neonatal
4. pathogen_directed_definitive_antibiotics Per organism + susceptibilities at 36-72 h culture-finalisation; narrow ampicillin alone for GBS; cefotaxime for E. coli meningitis (AVOID ceftriaxone <28 d) IV per pathogen (targeted_antimicrobial_per_culture, first line) — Stewardship and pathogen-directed narrowing per Puopolo 2018 + IDSA principles; ceftriaxone-avoid-<28-d is hard safety rule (bilirubin displacement + Ca-IVF incompatibility)

Setting playbook (ed) — Delivery-room or outside-hospital initial sepsis recognition; first-dose antibiotics within 60 min; cultures BEFORE antibiotics if possible without delay; coordinate NICU transfer (NICU-level handoff for "icu" setting in this schema vocabulary).
5. ampicillin 50 mg/kg IV 50 mg/kg IV q8h (term, week 1) / q12h (preterm <34 wks PMA) — EOS suspicion within 60 min (Empiric Gram-positive + Listeria coverage; Neofax 2024 + Puopolo 2018)
6. gentamicin 4 mg/kg IV 4 mg/kg (term) / 5 mg/kg (preterm <30 wks) IV q24-48h extended interval — EOS suspicion within 60 min (Gram-negative synergy; trough monitoring before 3rd dose (Neofax 2024))
7. acyclovir 20 mg/kg IV 20 mg/kg IV q8h (term) / q12h (preterm <30 wks PMA) — Active maternal HSV at delivery OR infant vesicular rash OR unexplained hepatitis / seizures (Empiric HSV cover (AAP Red Book 2024-2027 ch. HSV neonatal))

Non-pharmacologic actions:
- Thermoregulation (radiant warmer, plastic wrap if preterm)
- NICU transfer arrangements (icu setting in dossier vocabulary)
- Bag-mask ventilation or intubation as needed
- IV fluid bolus 10 mL/kg NS slowly if hypotensive; reassess

AVOID / contraindication checks:
- Ceftriaxone avoid under 28 days bilirubin displacement and calcium IVF incompatibility (FDA 2009; AAP Red Book 2024 2027)
- Sulfonamide avoid neonate bilirubin displacement (AAP Red Book 2024 2027)
- Nitrofurantoin avoid G6PD positive infant hemolysis trigger
- Aminoglycoside trough target <2 mcg per mL before 3rd dose (Neofax 2024)
- Acyclovir AKI monitor creatinine and hold if rising (Neofax 2024)
- Fluid bolus 10 to 20 mL per kg slower in neonate (AAP neonatal specific adaptation of SSC peds 2020)

Monitoring

Regimen monitoring:
- CBC + CRP at 24 + 48 h after first dose
- Blood culture follow-up at 36-48 h; stop antibiotics if negative + reassuring infant + normalized CRP (Puopolo 2018 stewardship)
- Gentamicin trough before 3rd dose (target < 2 mcg/mL)
- Repeat LP at 48 h if culture-positive meningitis
- Daily weight + intake / urine output + glucose q4-6h
- Hearing screen (AABR) before discharge — sensorineural hearing loss is meningitis sequela

Setting (ed) monitoring:
- Continuous cardiorespiratory + SpO₂
- Temperature q15-30 min until stabilized
- Glucose at presentation + q2h until feeding established or D10W IV

Follow-up plan: Pediatric follow-up within 24-48 h of discharge for high-risk; 1-week visit for all. Hearing screen (AABR) — sensorineural hearing loss is a sequela of bacterial meningitis. Neurodevelopmental peds at 6-12 mo for culture-positive meningitis or septic-shock survivors (Bayley III / ASQ-3). Immunization catch-up per ACIP schedule.
- Close-out criterion: Outpatient plan + hearing screen + neurodev follow-up scheduled

Monitoring phase: Continuous cardiorespiratory monitoring + SpO₂ + temperature. CBC + CRP at 24 + 48 h. Blood culture follow-up at 36-48 h. Gentamicin trough before 3rd dose (target < 2 mcg/mL). Repeat LP at 48 h if culture-positive meningitis. Glucose q4-6h. Stop antibiotics at 36-48 h if culture-negative + reassuring infant + normalized CRP / CBC per Puopolo 2018 stewardship.

Disposition

Current setting: ed — Delivery-room or outside-hospital initial sepsis recognition; first-dose antibiotics within 60 min; cultures BEFORE antibiotics if possible without delay; coordinate NICU transfer (NICU-level handoff for "icu" setting in this schema vocabulary).

Disposition criteria:
- Transfer to NICU (icu) once stabilized + empiric antibiotics in

Escalation triggers (move to higher acuity):
- Persistent hypotension despite 20-40 mL/kg fluid → vasoactive + ICU
- Refractory hypoxemia → intubation + transfer
- Seizure → phenobarbital load + LP plan

Earlier-Return Triggers

- No severity triggers declared for this engine.

Citations

- Puopolo KM et al — AAP 2018 Management of Neonates ≥35 0/7 wk With Suspected/Proven EOS (Pediatrics 2018 PMID 30455342) + companion preterm ≤34 6/7 wk (PMID 30455344); Kaiser EOS calculator Kuzniewicz 2017 (JAMA Peds PMID 28241253) for risk-based observation; Verani CDC 2010 GBS Prevention Guidelines (MMWR PMID 21088663) for IAP framework. [PMID:30455342](https://pubmed.ncbi.nlm.nih.gov/30455342/)
- Cited evidence (PMID 30455344) [PMID:30455344](https://pubmed.ncbi.nlm.nih.gov/30455344/)
- Cited evidence (PMID 28241253) [PMID:28241253](https://pubmed.ncbi.nlm.nih.gov/28241253/)
- Cited evidence (PMID 21088663) [PMID:21088663](https://pubmed.ncbi.nlm.nih.gov/21088663/)

Last reconciled with current guidelines: 2026-05-26.
References
  • Puopolo KM et al — AAP 2018 Management of Neonates ≥35 0/7 wk With Suspected/Proven EOS (Pediatrics 2018 PMID 30455342) + companion preterm ≤34 6/7 wk (PMID 30455344); Kaiser EOS calculator Kuzniewicz 2017 (JAMA Peds PMID 28241253) for risk-based observation; Verani CDC 2010 GBS Prevention Guidelines (MMWR PMID 21088663) for IAP framework. — PMID:30455342
  • Cited evidence (PMID 30455344) — PMID:30455344
  • Cited evidence (PMID 28241253) — PMID:28241253
  • Cited evidence (PMID 21088663) — PMID:21088663