Ampicillin

USE IF: Listeria meningitis (with gentamicin — synergy required); neonatal sepsis (with gentamicin); enterococcal infections including endocarditis — combination therapy required (ampicillin + gentamicin or ceftriaxone per guideline); intrapartum GBS prophylaxis when protocol-indicated; susceptible UTI. AVOID IF: Penicillin anaphylaxis; Epstein–Barr virus infection; Listeria / Enterococcus serious infection without guideline-directed combination therapy (NO ampicillin monotherapy); suspected β-lactamase–producing organisms (E. coli, H. influenzae, S. aureus) without susceptibility. PO NOT appropriate for meningitis, bacteremia, endocarditis, or neonatal sepsis — IV only; PO for mild or step-down. Active against many streptococci, Enterococcus, and Listeria; not reliable vs typical β-lactamase producers or MRSA.

• Primary: Listeria meningitis (2 g IV q4h adult, ≈12 g/day — CNS penetration; peds 200–300 mg/kg/day ÷ q4h IV; with gentamicin — NO monotherapy); neonatal sepsis (with gentamicin; NICU/GA protocol); enterococcal infection / endocarditis (combination per guideline); GBS prophylaxis (intrapartum); susceptible UTI
• Secondary: Endocarditis → combination therapy required (ampicillin + gentamicin or ceftriaxone per guideline); community-acquired pneumonia when susceptible; SSTI (streptococci); intra-abdominal infection in combination therapy
• Other: Typhoid when susceptible; Lyme disease IV alternative per guideline

• History of IgE-mediated penicillin hypersensitivity (e.g., anaphylaxis) → absolute contraindication
• Use caution: EBV infection (rash)
• Use caution: Renal impairment (seizure and crystalluria risk)
• Use caution: Allopurinol (rash), warfarin (INR), methotrexate (toxicity)
• Use caution: Frail elderly and polypharmacy

• Gentamicin (and other aminoglycosides) — REQUIRED synergy partner for Listeria meningitis, enterococcal endocarditis, and selected serious enterococcal infections per guideline; ampicillin monotherapy = treatment failure risk — NEVER mix in same IV line (inactivation)
• Warfarin → ↑ INR (monitor)
• Methotrexate → ↑ toxicity
• Allopurinol → ↑ rash risk
• Aminoglycosides → physical inactivation if mixed in solution / same line — separate lines and flush
• Probenecid → ↑ ampicillin levels
• Tetracyclines → ↓ efficacy

PO: take on an empty stomach (≥1 h before or 2 h after food) with water — oral absorption is significantly reduced with food; do not use PO for meningitis, bacteremia, neonatal sepsis, or endocarditis (IV only for these). IV: slow push (3–5 min) or infusion (15–30 min) per policy. Do NOT mix or Y-site with aminoglycosides — separate lines and flush between agents.

• Labs: renal function; CBC with prolonged courses; INR if on warfarin
• Clinical: neurologic status (seizures); rash or anaphylaxis; diarrhea suggesting CDAD; urine output (crystalluria risk)
• No clinical improvement at 48–72h → reassess diagnosis, resistance, source control, and drug interactions (DO NOT continue blindly)
• If targets not met after reassessment of dose, organ function, and interactions → escalate per protocol (DO NOT continue blindly)

- Oral bioavailability ~40% (↓ with food) - Distribution: ~0.4 L/kg - Low protein binding - Renal elimination - t½ prolonged in ESRD - β-lactam: time-dependent killing

Binds penicillin-binding proteins, inhibiting peptidoglycan cell wall synthesis with bactericidal activity in susceptible organisms. The aminopenicillin side chain improves entry into some gram-negative bacteria versus penicillin G.