## Empirical Antibiotic Therapy in Neonatal Sepsis (0–28 days) **Key Point:** The choice of empirical antibiotics in neonates depends critically on age, risk factors, and local epidemiology. For infants ≤7 days old (early-onset sepsis, EOS), the regimen must cover *Streptococcus agalactiae* (GBS), *Escherichia coli*, and *Listeria monocytogenes*. ### Standard Empirical Regimen for Neonatal Sepsis (0–28 days) | Parameter | Details | |-----------|----------| | **First-line combination** | Ampicillin + Gentamicin | | **Ampicillin dose** | 50 mg/kg/dose IV/IM every 12 h (≤7 days) | | **Gentamicin dose** | 7.5 mg/kg/dose IV/IM once daily | | **Coverage** | GBS, *E. coli*, *L. monocytogenes*, gram-negatives | | **Meningitis coverage** | Adequate for GBS and *L. monocytogenes*; gentamicin penetrates CSF | **High-Yield:** Ampicillin is essential because it is the only first-line agent that reliably covers *Listeria monocytogenes*. Third-generation cephalosporins (cefotaxime, ceftriaxone) do NOT cover *Listeria* and are therefore NOT used as monotherapy in neonates <28 days. ### Why NOT Third-Generation Cephalosporins Alone? 1. **Listeria gap:** *L. monocytogenes* is intrinsically resistant to all cephalosporins. 2. **Age-specific risk:** Neonates <28 days have higher risk of *Listeria* bacteremia (vertical transmission, contaminated food). 3. **Clinical consequence:** Using cefotaxime or ceftriaxone without ampicillin risks missing *Listeria* meningitis, a devastating infection with high mortality. **Clinical Pearl:** In infants >7 days with meningitis (CSF involvement), some centers add cefotaxime to ampicillin + gentamicin for enhanced CNS penetration, but ampicillin + gentamicin remains the backbone. **Mnemonic:** **AGE** = **A**mpicillin + **G**entamicin for neonatal **E**OS (early-onset sepsis). [cite:Nelson Textbook of Pediatrics 21e Ch 128]
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