EOS pathogens (vertical transmission) (Group B Streptococcus · Escherichia coli and other enteric Gram-negative bacilli · Listeria monocytogenes · less commonly H. influenzae, enterococci (AAP Red Book, WHO newborn infection guidance, CDC GBS prevention))
Clinical context (Suspected or confirmed invasive bacterial infection in first 72 hours of life (many guidelines ≤3 days) — maternal GBS colonization, chorioamnionitis, prolonged ROM, prematurity, or clinical signs of possible serious bacterial infection (PSBI))
First-line therapy
Ampicillin • i.v. • 50–50 mg/kg/dose • 3×/day
Max 2000 mg/dose · Max 8000 mg/day · Duration: 10–14 days · Non-meningitis neonatal sepsis — interval varies by GA/PNA (see high-dose indications); calculator uses 50 mg/kg q8h as term-neonate fallback
• Ampicillin interval nomogram (non-meningitis sepsis, Red Book/Nelson's): GA ≤34 weeks PNA 0–7 days 50 mg/kg q12h; GA >34 weeks PNA 0–7 days 50 mg/kg q12h (many NICUs transition to q8h after day 3–7); PNA 8–28 days 50 mg/kg q8h; PNA >28 days 50 mg/kg q6h. Adjust for renal dysfunction. **Calculator fallback: 50 mg/kg q8h** for term neonate — verify with NICU pharmacy table.
• Gentamicin extended-interval table (GA/PNA, Red Book/Nelson's): GA <30 weeks PNA ≤14 days **5 mg/kg q48h**; GA 30–34 weeks PNA ≤10 days **5 mg/kg q36h**; GA ≥35 weeks PNA ≤7 days **4 mg/kg q24h**; GA ≥35 weeks PNA 8–60 days **5 mg/kg q24h**. Do not use divided q8h dosing in neonates. **Calculator fallback: 5 mg/kg once daily** for term neonate — confirm interval with NICU protocol and TDM if therapy >48–72 h or renal impairment.
• Do not delay empiric IV antibiotics in a sick neonate — obtain blood culture (± surface cultures) before first dose when feasible without clinically meaningful delay; give ampicillin + gentamicin within 1 h of sepsis recognition per Surviving Sepsis Campaign pediatric principles adapted to neonates (WHO PSBI, AAP Red Book).
• If meningitis suspected or proven: switch to ampicillin + cefotaxime (not gentamicin monotherapy for CNS coverage) — see acute bacterial meningitis neonatal variant; gentamicin has poor meningeal penetration (AAP Red Book, WHO Pocket Book).
• CDC GBS EOS risk calculator (for well-appearing infants ≥35 weeks with chorioamnionitis or GBS risk): may support discontinuing empiric antibiotics at 36–48 h if blood culture negative and infant remains well — does NOT apply to ill-appearing infants or those with positive cultures; use as adjunct to clinical judgment, not substitute (CDC 2010/2024 update principles).
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Gentamicin • i.v./i.m. • 5–5 mg/kg/dose • 1×/day
Max 80 mg/dose · Duration: 10–14 days · Extended-interval aminoglycoside — dose and interval vary by GA/PNA and renal function (see high-dose indications); monitor levels if therapy >48–72 h
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Ampicillin • i.v. • 50–50 mg/kg/dose • 4×/day
Max 2000 mg/dose · Max 8000 mg/day · Duration: 14–21 days · Meningitis dose 200 mg/kg/day IV q6h — interval may be q8h–q12h in preterm neonates by GA/PNA (Red Book, Nelson's)
• Ampicillin + cefotaxime: suspected or proven meningitis, CSF pleocytosis, or neurologic signs (seizures, bulging fontanelle, altered tone) — mandatory ampicillin for Listeria; cefotaxime preferred over ceftriaxone in neonates (AAP Red Book, ESPID, WHO Pocket Book).
• Ampicillin + gentamicin remains first-line for EOS **without** meningitis — covers GBS, Listeria, and enteric Gram-negatives with aminoglycoside synergy; do not substitute cefotaxime for routine bacteremia unless meningitis concern (WHO PSBI, AAP).
• Vancomycin + gentamicin: rare in EOS — maternal MRSA colonization, nursery MRSA outbreak, or culture-proven MRSA; add ampicillin if Listeria/GBS still in differential (AAP Red Book).
• De-escalate at 48–72 h per cultures: narrow to penicillin G or ampicillin for GBS; tailor Gram-negative therapy to susceptibilities; stop vancomycin if MRSA not isolated (ESPID stewardship principles).
• Ampicillin/sulbactam is NOT recommended as neonatal EOS empiric therapy — limited sulbactam PK/safety data in neonates; use ampicillin + gentamicin per WHO/AAP/Red Book (Nelson's, UTMB neonatal manual).
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Cefotaxime • i.v. • 50–50 mg/kg/dose • 3×/day
Max 2000 mg/dose · Max 12000 mg/day · Duration: 14–21 days · Neonates: 50 mg/kg q8h (150 mg/kg/day); preferred third-generation cephalosporin over ceftriaxone in neonates (bilirubin displacement risk)
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Clinical notes
• EOS definition: invasive bacterial infection in first **72 hours** of life (AAP Red Book, CDC GBS prevention); some centers use **≤3 days** — distinct from late-onset sepsis (>72 h). Risk factors: maternal GBS colonization, chorioamnionitis, prolonged ROM ≥18 h, prematurity, maternal fever, inadequate intrapartum GBS prophylaxis.
• Blood cultures before antibiotics when feasible; obtain surface/cord cultures if indicated — do **not** delay empiric therapy in ill-appearing neonates (tachycardia, apnea, poor perfusion, lethargy, hypothermia, poor feeding). LP when meningitis suspected and safe to perform — treat empirically if LP deferred.
• Respiratory/cardiovascular support: supplemental O₂ for SpO₂ <90%, CPAP or mechanical ventilation for respiratory failure; IV fluid bolus 10–20 mL/kg for poor perfusion/shock; vasopressors/inotropes per NICU protocol for fluid-refractory shock (Surviving Sepsis Campaign pediatric adaptation, WHO PSBI).
• NICU admission: all neonates with suspected EOS requiring empiric IV antibiotics — continuous cardiorespiratory monitoring, serial clinical assessment, and repeat cultures if clinically deteriorating; well-appearing chorioamnionitis-exposed infants may be observed per CDC EOS calculator and local protocol.
• Duration by pathogen: GBS bacteremia without meningitis **10 days**; GBS meningitis **14–21 days**; E. coli/Gram-negative bacteremia **14 days** (21 if meningitis or slow response); Listeria **14–21 days**; discontinue at 48 h if cultures negative and infant well per CDC calculator/low-risk pathway only when appropriate (AAP Red Book, ESPID).
• AAP Red Book — Group B streptococcal disease and neonatal sepsis (2024)
• CDC — GBS prevention guidelines and neonatal EOS risk calculator (2024)
• WHO — Newborn possible serious bacterial infection (PSBI) and empiric ampicillin + gentamicin (2023)
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• ESPID — Neonatal infection and antimicrobial stewardship principles (2024)
