Amoxicillin-Clavulanate Dosing Recommendations
For adults with respiratory tract infections, use amoxicillin-clavulanate 875 mg/125 mg twice daily, or for more severe infections, 500 mg/125 mg three times daily. For children, high-dose amoxicillin-clavulanate (90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate in 2 divided doses) is the preferred regimen for most bacterial respiratory infections 1.
Adult Dosing
Standard dosing: Amoxicillin-clavulanate 500 mg/125 mg every 12 hours OR 250 mg/125 mg every 8 hours 1.
For severe infections or respiratory tract infections: Use 875 mg/125 mg every 12 hours OR 500 mg/125 mg every 8 hours 1.
The FDA label defines high-dose amoxicillin-clavulanate as 4 g of amoxicillin with 250 mg of clavulanate per day for adults 2. This high-dose regimen is specifically designed to overcome resistance in Streptococcus pneumoniae with elevated minimum inhibitory concentrations (MICs) and to cover β-lactamase-producing organisms 2.
Specific Adult Indications:
Acute bacterial rhinosinusitis: Amoxicillin-clavulanate is preferred over amoxicillin alone 3. High-dose formulations are recommended when resistance is suspected.
Community-acquired pneumonia: Standard to high-dose regimens depending on severity 4.
Skin and soft tissue infections: 875 mg/125 mg twice daily or 500 mg/125 mg three times daily 5, 6.
Pediatric Dosing
Age-Based Approach:
Neonates and infants <12 weeks (3 months): 30 mg/kg/day divided every 12 hours (based on amoxicillin component). Use the 125 mg/31.25 mg per 5 mL suspension 1.
Children ≥12 weeks (3 months):
The high-dose regimen is strongly preferred for most bacterial infections:
- 90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate in 2 divided doses (maximum 2 g per dose) 7, 3, 8, 1
This high-dose regimen is specifically recommended for:
- Acute otitis media 7
- Acute bacterial rhinosinusitis 3, 8
- Community-acquired pneumonia (in children <5 years with risk factors) 9
- β-lactamase-producing Haemophilus influenzae 4
Standard-dose alternative: 45 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate in 2 divided doses may be used for less severe infections 1.
Lower-dose option: 25 mg/kg/day every 12 hours OR 20 mg/kg/day every 8 hours for mild infections 1.
Pediatric Formulations:
The 14:1 ratio formulation (amoxicillin to clavulanate) is specifically designed for high-dose pediatric therapy and minimizes clavulanate-related diarrhea 2, 7, 2. The every 12-hour regimen is associated with significantly less diarrhea compared to every 8-hour dosing 7, 1.
Children weighing ≥40 kg: Dose according to adult recommendations 1.
Important Pediatric Considerations:
- Do NOT substitute two 250 mg/125 mg tablets for one 500 mg/125 mg tablet—they contain different amounts of clavulanate 1
- The 250 mg/125 mg tablet and 250 mg/62.5 mg chewable tablet are not interchangeable 1
- Recent evidence suggests lower clavulanate doses (80 mg/kg/day amoxicillin with 2.85 mg/kg/day clavulanate) may reduce diarrhea without compromising efficacy in acute otitis media 10
Specific Infection Guidelines
Acute Otitis Media (Children):
First-line: 90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate in 2 divided doses for 10 days 7. This is preferred over amoxicillin alone, especially if the child received amoxicillin in the previous 30 days or has concurrent conjunctivitis 7.
Acute Bacterial Rhinosinusitis:
- Children: Amoxicillin-clavulanate is preferred over amoxicillin alone 3, 8. Use 90 mg/kg/day (amoxicillin component) in 2 divided doses.
- Adults: Amoxicillin-clavulanate is recommended, though the evidence is weaker than in children 3. High-dose formulations (2 g twice daily) are preferred when resistance is suspected 3.
Community-Acquired Pneumonia:
- Children <3 years: Amoxicillin 80-100 mg/kg/day is first-line 9. Amoxicillin-clavulanate (80 mg/kg/day) is reserved for inadequately vaccinated children or those with concurrent purulent otitis media 9.
- Children ≥3 years: Base choice on clinical presentation—amoxicillin for pneumococcal pneumonia, macrolides for atypical pathogens 9.
- Adults: Standard to high-dose regimens depending on severity 4.
β-lactamase-Producing Haemophilus influenzae:
Use amoxicillin-clavulanate 45 mg/kg/day (amoxicillin component) in 3 doses OR 90 mg/kg/day in 2 doses 4.
Renal Impairment Dosing
GFR 10-30 mL/min: 500 mg/125 mg or 250 mg/125 mg every 12 hours 1.
GFR <10 mL/min: 500 mg/125 mg or 250 mg/125 mg every 24 hours 1.
Hemodialysis: 500 mg/125 mg or 250 mg/125 mg every 24 hours, with an additional dose during and at the end of dialysis 1.
Do NOT use the 875 mg/125 mg dose in patients with GFR <30 mL/min 1.
Administration Considerations
- Take at the start of meals to enhance clavulanate absorption and minimize gastrointestinal intolerance 1
- Twice-daily dosing is as effective as three-times-daily dosing and improves compliance 11, 12
- Duration: 5-7 days for uncomplicated adult infections; 10-14 days for pediatric infections 3, 8
Common Pitfalls
Do not use first-generation cephalosporins (e.g., cephalexin) for infections where amoxicillin-clavulanate is indicated—they lack activity against key pathogens 4, 13.
Avoid underdosing in children: The high-dose regimen (90 mg/kg/day) is necessary to overcome resistance, particularly in acute otitis media and sinusitis 7, 3, 8.
Watch for formulation errors: Different tablet strengths contain different amounts of clavulanate and are not interchangeable 1.
Recent evidence questions high-dose benefit in adults: A 2021 trial found no superiority of high-dose over standard-dose amoxicillin-clavulanate for acute sinusitis in adults, though diarrhea rates were similar 14. However, guidelines still recommend high-dose for suspected resistance 3.