What is the recommended dose of amoxicillin (amoxiclav) / clavulanic acid for treating bacterial infections?

Amoxicillin-Clavulanate (Amoxiclav) Dosing for Bacterial Infections

For most adult bacterial infections, amoxicillin-clavulanate 875/125 mg twice daily is the recommended standard dose, while high-dose formulations (2000/125 mg twice daily) should be reserved for severe infections or when resistant organisms are suspected. 1, 2

Standard Adult Dosing Regimens

Mild-to-Moderate Infections

• 500 mg amoxicillin/125 mg clavulanate three times daily provides adequate coverage for uncomplicated infections 1, 3
• This regimen is appropriate for animal bites, human bites, and mild skin/soft tissue infections 1

Respiratory Tract Infections (Preferred)

• 875 mg amoxicillin/125 mg twice daily is specifically recommended for acute bacterial rhinosinusitis, community-acquired pneumonia, and acute exacerbations of chronic bronchitis 1, 3, 2
• The FDA label confirms this as the standard dose for severe infections and respiratory tract infections 2
• Duration: 5-7 days for uncomplicated acute bacterial rhinosinusitis in adults 1, 3

High-Dose Formulations

When to Use High-Dose (2000/125 mg twice daily)

High-dose amoxicillin-clavulanate is indicated when bacterial resistance is likely or infection is severe. 1 Specific situations include:

• Recent antibiotic use (within the past month) 1
• Geographic regions with high rates (>10%) of penicillin-nonsusceptible Streptococcus pneumoniae 1
• Severe infection: Temperature ≥39°C (102°F), systemic toxicity, or threat of suppurative complications 1
• Age >65 years 1
• Recent hospitalization 1
• Immunocompromised patients 1
• Comorbidities: diabetes, chronic cardiac/hepatic/renal disease 1
• Close contact with daycare facilities or healthcare environments 1
• Smokers or household members who smoke 1
• Frontal or sphenoidal sinusitis 1
• History of recurrent infections 1
• Failure of prior antibiotic therapy 1

High-Dose Efficacy Evidence

• The 2000/125 mg twice-daily formulation achieves higher amoxicillin serum concentrations for longer periods, providing coverage against S. pneumoniae with MICs up to 4 mg/L 4
• Clinical success rates of 91.5% were demonstrated for community-acquired pneumonia, comparable to standard dosing 4
• Superior tissue penetration and pharmacodynamic parameters were observed compared to 500/125 mg three times daily 5

However, a 2021 randomized trial found no benefit of high-dose over standard-dose for clinically diagnosed acute sinusitis (44.3% vs 36.4% improvement at day 3, p=0.35), with similar rates of severe diarrhea (7.0% vs 7.7%) 6. This suggests high-dose may not be necessary for routine sinusitis without risk factors.

Pediatric Dosing

• Standard dose: 45 mg/kg/day of amoxicillin component divided twice daily 7
• High-dose: 90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate, divided twice daily 1
• Duration: 10-14 days for acute bacterial rhinosinusitis in children 1
• High-dose formulation effectively eradicates penicillin-resistant S. pneumoniae (MICs 2-4 mg/L) 7

Special Populations

Renal Impairment

• Do not use the 875 mg dose if GFR <30 mL/min 2
• Dose adjustment required for severe renal impairment 2

Penicillin-Allergic Patients

• Use doxycycline (100 mg twice daily) or respiratory fluoroquinolones (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) instead 1
• For non-type I hypersensitivity: clindamycin plus third-generation cephalosporin (cefixime or cefpodoxime) 1

Administration Guidelines

• Take at the start of meals to enhance clavulanate absorption and minimize gastrointestinal intolerance 2
• Twice-daily dosing reduces diarrhea frequency compared to three-times-daily regimens 7, 8
• Never substitute two 250 mg tablets for one 500 mg tablet, as this results in excessive clavulanate dosing 3

Critical Dosing Pitfalls

• Avoid macrolides and trimethoprim-sulfamethoxazole as first-line therapy due to high resistance rates (>40% for macrolides, 50% for TMP-SMZ against S. pneumoniae) 1
• Fluoroquinolones should not be first-line in non-penicillin-allergic patients despite comparable efficacy, due to higher adverse event rates 1
• Complete the full treatment course to prevent treatment failure and resistance development 3
• The 875/125 mg twice-daily formulation is as effective and safe as 500/125 mg three times daily for acute bacterial sinusitis 8