Amoxicillin-Clavulanate Dosing for Infection
For adults with most infections, use amoxicillin-clavulanate 875/125 mg twice daily; for more severe infections or respiratory tract infections, this same dose is appropriate, or alternatively 500/125 mg three times daily. 1
Standard Adult Dosing
The FDA-approved dosing regimen is straightforward 1:
- Usual dose: 500/125 mg every 12 hours OR 250/125 mg every 8 hours
- More severe infections and respiratory tract infections: 875/125 mg every 12 hours OR 500/125 mg every 8 hours
Take at the start of meals to minimize gastrointestinal side effects and enhance clavulanate absorption 1
Infection-Specific Dosing
Skin and Soft Tissue Infections
For impetigo and other skin infections, 875/125 mg twice daily is recommended 2. For animal or human bite wounds requiring treatment, this same dose provides appropriate coverage against the polymicrobial flora including Pasteurella species, S. aureus, and anaerobes 3.
Acute Bacterial Rhinosinusitis
High-dose amoxicillin-clavulanate (2 g/125 mg twice daily or 90 mg/kg/day in children) is recommended for initial empiric therapy 4. This higher dose is particularly important when:
- Recent antibiotic use within 4-6 weeks
- Geographic areas with high rates of drug-resistant S. pneumoniae
- Moderate to severe disease 5, 4
Recent evidence suggests that immediate-release high-dose formulations (1750 mg twice daily) may provide more rapid symptom improvement compared to standard dosing, though with increased risk of severe diarrhea (15.8% vs 4.8%) 6.
Community-Acquired Pneumonia
For hospitalized patients without ICU admission, amoxicillin-clavulanate can be used as the β-lactam component at 875/125 mg twice daily, combined with a macrolide 7. For outpatients with comorbidities, high-dose amoxicillin (1 g three times daily) or amoxicillin-clavulanate (2 g twice daily) plus a macrolide is preferred 7.
Chronic Rhinosinusitis
Amoxicillin-clavulanate 625 mg three times daily for 3 weeks showed comparable efficacy to clarithromycin in one trial, though data are limited 8. The 875/125 mg twice daily formulation for 14 days demonstrated superior early response compared to cefuroxime 8.
Intra-Abdominal Infections
While not a first-line agent for complicated intra-abdominal infections, when used, standard dosing applies. Piperacillin-tazobactam or carbapenems are generally preferred for these infections 9.
Pediatric Dosing
For children ≥3 months old 1:
- Otitis media, sinusitis, lower respiratory tract infections: 45 mg/kg/day (of amoxicillin component) divided every 12 hours using the 200 mg/5 mL or 400 mg/5 mL suspension
- Less severe infections: 25 mg/kg/day divided every 12 hours
- Duration for acute otitis media: 10 days
The every-12-hour regimen is preferred over every-8-hour dosing due to significantly less diarrhea 1.
Renal Impairment Adjustments
Critical dosing modifications are required for renal dysfunction 1:
- GFR <30 mL/min: Do NOT use the 875/125 mg dose
- GFR 10-30 mL/min: 500/125 mg or 250/125 mg every 12 hours
- GFR <10 mL/min: 500/125 mg or 250/125 mg every 24 hours
- Hemodialysis: 500/125 mg or 250/125 mg every 24 hours, with additional doses during and after dialysis
Important Caveats
Do not substitute two 250/125 mg tablets for one 500/125 mg tablet - they contain different amounts of clavulanate (250 mg vs 125 mg total) and are not equivalent 1.
For severe infections, particularly those caused by Enterobacteriaceae, some evidence suggests that increasing to 6 times daily dosing may be necessary to achieve adequate pharmacodynamic targets (40% time above MIC), as only 65% of hospitalized patients reached this target with standard dosing for organisms with MIC of 8 mg/L 10.
The combination is in the WHO AWaRe "Access" category, supporting its role as a stewardship-aligned first-line agent when β-lactamase-producing organisms are suspected 11, 12.