Optimal Amoxicillin Dosing for Susceptible Organisms
For amoxicillin-susceptible infections, standard-dose amoxicillin (45 mg/kg/day in children or 500 mg three times daily in adults) is appropriate for mild-to-moderate infections, while high-dose amoxicillin (80-90 mg/kg/day in children or 875 mg twice daily in adults) should be used for severe infections, high-risk patients, or when enhanced tissue penetration is needed. 1, 2
Pediatric Dosing
Standard-Dose Regimen (Mild-to-Moderate Infections)
- 45 mg/kg/day divided into 2 doses for children ≥2 years without recent antibiotic exposure or daycare attendance 1
- Maximum 500 mg per dose 2
- Appropriate for uncomplicated respiratory tract infections when antimicrobial resistance is not suspected 1
High-Dose Regimen (Severe Infections or High-Risk Patients)
- 80-90 mg/kg/day divided into 2 doses for children with: 1
- Age <2 years
- Recent antibiotic use (within 4-6 weeks)
- Daycare attendance
- Moderate-to-severe illness
- Geographic areas with >10% penicillin-resistant S. pneumoniae 1
- Maximum 2 grams per dose 1
- This dosing achieves tissue concentrations sufficient to overcome intermediate penicillin resistance 1
Special Pediatric Populations
- Neonates and infants ≤3 months: Maximum 30 mg/kg/day divided every 12 hours 2
- Community-acquired pneumonia: 50-75 mg/kg/day in 2 doses for Group A Streptococcus 1
- Haemophilus influenzae (β-lactamase negative): 75-100 mg/kg/day in 3 doses 1
Adult Dosing
Standard-Dose Regimen
- 500 mg orally three times daily for most susceptible infections 3, 2
- Appropriate for dental infections, uncomplicated respiratory infections, and skin/soft tissue infections 3
- Duration typically 7-10 days depending on infection type 3
High-Dose Regimen
- 875 mg twice daily for severe infections or enhanced tissue penetration 2, 4
- Provides comparable efficacy to 500 mg three times daily with improved convenience 4
- Maintains therapeutic concentrations above MIC for approximately 40% of dosing interval for organisms with MIC ≤4 mg/L 5
Severe Infections Requiring Parenteral Therapy
- Intravenous ampicillin 150-200 mg/kg/day divided every 6 hours for hospitalized patients with susceptible organisms 1
- Consider transition to oral therapy once clinically stable 1
Pharmacodynamic Considerations
Time Above MIC Target
- Amoxicillin requires ≥40% time above MIC (T>MIC) for optimal bactericidal activity 6, 5
- Standard dosing achieves this target for organisms with MIC ≤2 mg/L 7
- High-dose regimens extend coverage to organisms with MIC up to 4 mg/L 5, 7
Dosing Frequency
- Twice-daily dosing is as effective as three-times-daily for most infections when total daily dose is equivalent 4
- Improves adherence without compromising efficacy 4
Duration of Therapy
Infection-Specific Durations
- Respiratory tract infections: 5-7 days for uncomplicated cases 1, 8
- Dental infections: 7-10 days (always with source control) 3
- Skin/soft tissue infections: 5-7 days with adequate source control 1
- Intra-abdominal infections: 4 days if adequate source control achieved 1
Shorter Course Evidence
- 3-day courses may be non-inferior to 7-day courses for uncomplicated community-acquired pneumonia in children, though cough resolution is slightly delayed 8
- Shorter courses reduce antimicrobial resistance risk without increasing treatment failure 8
Critical Pitfalls to Avoid
Underdosing High-Risk Patients
- Do not use standard-dose amoxicillin in children <2 years, those with recent antibiotic exposure, or daycare attendees—these populations require high-dose therapy 1
- Geographic resistance patterns matter: areas with >10% penicillin-resistant S. pneumoniae warrant empiric high-dose therapy 1
Inadequate Source Control
- Amoxicillin alone is insufficient for abscesses or collections requiring drainage 3
- Dental abscesses require extraction, root canal, or incision/drainage—antibiotics are adjunctive only 3