Amoxicillin-Clavulanate Dosing for Adults
For adults with mild to moderate infections, the standard dose is 500 mg/125 mg every 8 hours or 875 mg/125 mg every 12 hours, but for respiratory infections with risk factors for resistance or moderate-to-severe disease, use the high-dose regimen of 2000 mg/125 mg twice daily. 1, 2, 3
Standard Adult Dosing
- Mild to moderate infections: 500 mg/125 mg every 8 hours OR 875 mg/125 mg every 12 hours 3
- Respiratory tract infections without risk factors: 625 mg (500 mg/125 mg) three times daily 1, 4
- The FDA-approved usual adult dose is one 500 mg/125 mg tablet every 12 hours or one 250 mg/125 mg tablet every 8 hours 3
High-Dose Regimen for Resistant Pathogens
Use 2000 mg/125 mg twice daily when any of the following risk factors are present: 1, 2
- Antibiotic use within the past 4-6 weeks 1, 2
- Age >65 years 2
- Recent hospitalization 2
- Immunocompromised status 2
- Geographic regions with >10% penicillin-resistant Streptococcus pneumoniae 1, 2
- Close contact with daycare facilities 2
- Smoking or household smoker exposure 2
- Moderate to severe symptoms (fever ≥39°C, systemic toxicity) 2
- Frontal or sphenoidal sinusitis 2
- Comorbid conditions (diabetes, chronic cardiac/hepatic/renal disease) 2
The 2000 mg/125 mg formulation uses a pharmacokinetically enhanced, modified-release mechanism that maintains therapeutic amoxicillin levels for approximately 49% of the 12-hour dosing interval at an MIC of 4 mcg/mL—a level unachievable with conventional formulations. 5 This extended coverage is critical for eradicating penicillin-resistant S. pneumoniae with MICs up to 4-8 mg/L. 6, 7
Treatment Duration by Indication
- Acute bacterial rhinosinusitis: 5-7 days 1, 2
- Community-acquired pneumonia: 7-10 days 4
- Acute exacerbations of chronic bronchitis: 5 days with high-dose formulation is as effective as 7 days with standard dosing 8
- Uncomplicated urinary tract infections: 3-7 days 4
Administration Guidelines
- Take at the start of a meal to enhance clavulanate absorption and minimize gastrointestinal intolerance 3
- Evaluate clinical response within 48-72 hours; if no improvement, consider changing antibiotics or reevaluating the diagnosis 1, 4
Critical Dosing Pitfalls to Avoid
Do NOT substitute two 250 mg/125 mg tablets for one 500 mg/125 mg tablet—they contain the same amount of clavulanate (125 mg each), making them non-equivalent. 3 This is a common prescribing error that results in clavulanate overdosing.
Avoid underdosing in high-resistance areas: In regions where penicillin-resistant S. pneumoniae prevalence exceeds 10%, always use the high-dose formulation (2000 mg/125 mg twice daily) to achieve adequate serum concentrations. 1, 2
Do NOT use macrolides or trimethoprim-sulfamethoxazole as alternatives due to resistance rates exceeding 40% for macrolides and 50% for TMP-SMX against S. pneumoniae. 2
Alternative Therapies for Penicillin Allergy
- Type I hypersensitivity: Use doxycycline or respiratory fluoroquinolones (levofloxacin or moxifloxacin) 1, 2
- Non-Type I hypersensitivity: Consider clindamycin plus a third-generation oral cephalosporin 2
The high-dose formulation has demonstrated equivalent or superior clinical efficacy (91.5-93% success rates) compared to standard dosing in community-acquired pneumonia, with no difference in adverse event rates. 7, 8