A 3-day-old term neonate born to a mother with prolonged rupture of membranes (>18 hours) presents with fever, lethargy, and poor feeding. Blood culture is pending. What is the first-line antibiotic regimen for presumed early-onset neonatal sepsis in this infant?

Explanation

## First-Line Empiric Therapy for Early-Onset Neonatal Sepsis **Key Point:** Ampicillin + Gentamicin is the gold-standard first-line regimen for presumed early-onset neonatal sepsis (EOS) in the first 72 hours of life. ### Rationale Early-onset sepsis (EOS) is typically caused by maternal flora acquired during delivery: - **Group B Streptococcus (GBS)** — most common - **Gram-negative enterobacteria** (E. coli, Klebsiella) - **Listeria monocytogenes** — less common but important Ampicillin provides coverage of GBS and Listeria (unlike cephalosporins, which do NOT cover Listeria), while gentamicin covers gram-negative organisms synergistically. ### Dosing in Neonates | Drug | Dose | Interval (age-dependent) | | --- | --- | --- | | Ampicillin | 50 mg/kg/dose IV/IM | Q12h (0–7 days); Q8h (>7 days) | | Gentamicin | 7.5 mg/kg/dose IV/IM | Q24h (0–7 days); Q18h (>7 days) | **Clinical Pearl:** Gentamicin dosing in neonates differs from older children — once-daily dosing is preferred in the first week of life due to immature renal function and reduced clearance. **High-Yield:** The combination covers the "big three" pathogens of EOS: GBS, E. coli, and Listeria. This regimen is recommended by AAP, CDC, and ACOG guidelines. ### Duration - If blood culture is negative and clinical improvement occurs: **7–10 days** - If culture is positive or meningitis is confirmed: **10–14 days** (or longer if CNS involvement) **Warning:** Do NOT use cephalosporins (ceftriaxone, cefotaxime) as monotherapy for presumed EOS because they lack coverage of Listeria monocytogenes, which, though rare (1–2% of EOS), can cause severe meningitis in neonates. [cite:AAP Neonatal Resuscitation Program, Harrison 21e Ch 169]