What defines high‑dose oral Augmentin (amoxicillin‑clavulanate) and what are the recommended dosing regimens, including renal‑function adjustments and alternative therapies?

High-Dose Oral Augmentin: Definition and Dosing

High-dose oral Augmentin is defined as amoxicillin 2000 mg/clavulanate 125 mg twice daily for adults, or 90 mg/kg/day amoxicillin with 6.4 mg/kg/day clavulanate divided twice daily for children, designed to achieve adequate serum concentrations to eradicate penicillin-resistant Streptococcus pneumoniae with MICs up to 4-8 mg/L. 1

Standard vs. High-Dose Formulations

Adult Dosing

Standard-dose regimens:

• 875 mg/125 mg twice daily for respiratory infections 2
• 500 mg/125 mg three times daily for mild-to-moderate infections 2

High-dose regimen:

• 2000 mg/125 mg twice daily, providing superior pharmacodynamic coverage with 90-92% predicted clinical efficacy versus 83-88% for standard dosing 1, 3
• This formulation extends therapeutic amoxicillin levels over the 12-hour dosing interval to eradicate strains with amoxicillin MICs ≤4 mg/L 4, 5

Pediatric Dosing

Standard-dose:

• 45 mg/kg/day amoxicillin component with 6.4 mg/kg/day clavulanate, divided twice daily 1, 3

High-dose:

• 90 mg/kg/day amoxicillin with 6.4 mg/kg/day clavulanate, divided twice daily (maximum 4000 mg/day amoxicillin) 1, 3
• The 14:1 ratio of amoxicillin to clavulanate in high-dose formulations causes less diarrhea than other preparations 3

Indications for High-Dose Therapy

High-dose Augmentin is indicated when ANY of the following risk factors are present: 1, 3

• Recent antibiotic use within the past 4-6 weeks
• Age >65 years
• Daycare attendance or close contact with daycare children
• Moderate-to-severe infection severity
• Frontal or sphenoidal sinusitis
• History of recurrent infections
• Comorbidities (diabetes, chronic cardiac/pulmonary/hepatic/renal disease)
• Immunocompromised status
• Smoking or exposure to smokers
• Geographic areas with >10% prevalence of penicillin-resistant S. pneumoniae
• Prior antibiotic treatment failure
• Healthcare environment exposure
• Concurrent purulent conjunctivitis (pediatrics) 1, 3

Treatment Duration by Indication

Acute bacterial rhinosinusitis:

• Adults: 5-7 days (as effective as 10 days with fewer adverse effects) 1, 3
• Children: 10-14 days 1, 3

Community-acquired pneumonia:

• 7-10 days, may extend to 14 days based on clinical response 2, 1
• Continue until afebrile for 48 hours and clinically stable 2

Acute exacerbations of chronic bronchitis:

• High-dose 2000/125 mg for 5 days is as effective as standard-dose 875/125 mg for 7 days 6

Skin and soft tissue infections:

• 7-10 days depending on severity 2

Renal Function Adjustments

For creatinine clearance 10-30 mL/min:

• Reduce dosing frequency to every 12 hours OR decrease dose by 50% 1

For creatinine clearance <10 mL/min:

• Reduce dosing frequency to every 24 hours OR decrease dose by 75% 1

Hemodialysis patients:

• Administer supplemental dose after each dialysis session 1

Clinical Reassessment Algorithm

Adults:

• At 3-5 days: If no improvement, escalate to high-dose formulation or switch to respiratory fluoroquinolone 3
• At 7 days: Persistent/worsening symptoms require diagnostic reconsideration, imaging, and ENT referral 3

Children:

• At 72 hours: Lack of improvement or worsening warrants escalation to high-dose formulation 3

Critical Prescribing Pitfalls

Never substitute two 250 mg tablets for one 500 mg tablet - this results in excessive clavulanate dosing and increased gastrointestinal side effects 2

Avoid antibiotics for symptom duration <10 days unless severe features present (fever ≥39°C with purulent nasal discharge for ≥3 consecutive days), as 98-99.5% of acute rhinosinusitis cases are viral 3

Complete the full course - minimum 5 days for adults and 10 days for children to prevent treatment failure, resistance development, and complications such as acute rheumatic fever 2, 3

For patients ≥40 kg, use adult dosing rather than pediatric weight-based calculations to avoid dosing errors 3

Alternative Therapies

For penicillin-allergic patients:

• Adults: Doxycycline or respiratory fluoroquinolones (levofloxacin, moxifloxacin) 3
• Children with non-type I allergy: Clindamycin plus third-generation oral cephalosporin 3

For patients unable to tolerate oral medication:

• Ceftriaxone 1 gram IM/IV daily for 5 days 3

Pharmacodynamic Advantages

The high-dose 2000/125 mg formulation achieves:

• Extended time above MIC (T>MIC) of 40-66% for tissue concentrations when MIC is 1 mcg/mL, compared to 40-52% for standard dosing 7
• Superior tissue inhibitory quotients against S. pneumoniae, H. influenzae, M. catarrhalis, and S. pyogenes 7
• Clinical and bacteriological success rates of 91.5% and 90.6% respectively in community-acquired pneumonia 5

Gastrointestinal adverse events occur in approximately 15-40% of patients but rarely require discontinuation 1, 8