Amoxicillin-Clavulanate (Amoxyclav): Comprehensive Dosing and Clinical Guide
Adult Dosing Regimens
For most community-acquired respiratory tract infections in adults, amoxicillin-clavulanate 500 mg/125 mg three times daily or 875 mg/125 mg twice daily for 7-10 days is the standard regimen. 1, 2
Standard-Dose Adult Therapy
- 500 mg/125 mg three times daily for uncomplicated respiratory infections, skin infections, and urinary tract infections 2
- 875 mg/125 mg twice daily is an alternative standard regimen with equivalent efficacy and improved compliance 3, 4
- Duration: 5-7 days for acute bacterial rhinosinusitis, 7-10 days for pneumonia, 14 days for bronchiectasis exacerbations 1, 2
High-Dose Adult Therapy
High-dose amoxicillin-clavulanate (2000 mg/125 mg twice daily) is indicated for adults with risk factors for resistant organisms. 1, 2
Risk factors requiring high-dose therapy include: 2
- Recent antibiotic use within 4-6 weeks
- Moderate to severe disease presentation
- Age >65 years
- Smoking or exposure to secondhand smoke
- Immunocompromised status
- Comorbidities (diabetes, heart/lung/liver/kidney disease)
- Geographic areas with >10% penicillin-resistant S. pneumoniae
- Failed previous antibiotic therapy
- Frontal or sphenoidal sinusitis
The high-dose formulation achieves adequate tissue concentrations to overcome penicillin-resistant S. pneumoniae and β-lactamase-producing organisms. 1, 5
Pediatric Dosing Regimens
For children with respiratory infections, the standard dose is 45 mg/kg/day of amoxicillin component divided into 2-3 doses, while high-risk children require 90 mg/kg/day divided into 2 doses (maximum 4000 mg/day). 6, 7
Standard-Dose Pediatric Therapy
- 45 mg/kg/day divided into 2 doses for uncomplicated infections 6
- Alternative: 45 mg/kg/day divided into 3 doses 1
- Maximum single dose: 2000 mg per dose regardless of weight 6
High-Dose Pediatric Therapy (90 mg/kg/day)
High-dose amoxicillin-clavulanate (90 mg/kg/day amoxicillin with 6.4 mg/kg/day clavulanate in 2 divided doses) is the preferred regimen for children with specific risk factors. 6, 7
Risk factors requiring high-dose therapy in children: 6, 2
- Age <2 years
- Daycare attendance
- Recent antibiotic use within 30 days
- Moderate to severe illness
- Incomplete Haemophilus influenzae type b vaccination (<3 doses)
- Concurrent purulent otitis media
- Geographic areas with >10% penicillin-resistant S. pneumoniae
- Concurrent conjunctivitis (requires Moraxella catarrhalis coverage)
Age-Based Pediatric Dosing (Standard Formulations)
For children without risk factors: 6
- <1 year (1-12 months): 2.5 mL of 125/31 suspension three times daily
- 1-6 years: 5 mL of 125/31 suspension three times daily
- 7-12 years: 5 mL of 250/62 suspension three times daily
- 12-18 years: 1 tablet (250/125) three times daily
Critical Warning: The 600 mg/42.9 mg per 5 mL formulation is NOT interchangeable with other suspensions due to different clavulanate ratios. 7
Specific Infection Types and Durations
Community-Acquired Pneumonia
Children <3 years: Start with amoxicillin alone 80-100 mg/kg/day in 3 divided doses for 10 days. 1, 6 Add clavulanate (80 mg/kg/day amoxicillin component) only if incomplete H. influenzae type b vaccination or concurrent purulent otitis media. 1, 6
Children ≥3 years: Base initial therapy on clinical presentation—amoxicillin for pneumococcal pneumonia, macrolide for atypical pathogens. 1
Adults: Standard-dose amoxicillin-clavulanate for 7-10 days; high-dose for risk factors. 2
Acute Bacterial Rhinosinusitis
Adults: 5-7 days of therapy is as effective as 10 days. 2 Use standard-dose unless risk factors present, then high-dose. 1
Children: 10-14 days of therapy recommended. 1, 6 High-dose for risk factors. 1, 6
Reassessment at 72 hours: If no improvement or worsening, switch antibiotics or obtain imaging/cultures. 1, 2
Acute Bronchiolitis
Antibiotics are NOT routinely indicated due to predominantly viral etiology. 1 Consider amoxicillin-clavulanate only for: 1
- Fever ≥38.5°C persisting >3 days
- Associated purulent acute otitis media
- Pneumonia/atelectasis confirmed on chest X-ray
Duration: 5-8 days when indicated. 1
Pharmacokinetic Advantages and Formulation Considerations
The twice-daily formulations contain higher amoxicillin relative to clavulanate, improving compliance and reducing gastrointestinal side effects without compromising efficacy. 3, 5
Key Pharmacokinetic Points
- Both components are rapidly absorbed, reaching peak levels in 40-120 minutes 8
- Half-life: 45-90 minutes for both components 8
- Absorption enhanced when taken at the start of a meal 7
- The 14:1 ratio (90 mg/6.4 mg per kg) causes significantly less diarrhea than older formulations 6, 3
Critical Formulation Warnings
Do NOT substitute different suspension concentrations—they are not interchangeable. 7 The 600 mg/42.9 mg per 5 mL formulation contains different clavulanate amounts than 200 mg/28.5 mg or 400 mg/57 mg suspensions. 7
Antimicrobial Spectrum and Resistance Considerations
Amoxicillin-clavulanate provides coverage against β-lactamase-producing H. influenzae, M. catarrhalis, and methicillin-sensitive S. aureus, while maintaining activity against S. pneumoniae. 1, 5
Covered Organisms
- Streptococcus pneumoniae (including intermediately resistant strains with high-dose) 1, 5
- β-lactamase-producing Haemophilus influenzae 1
- Moraxella catarrhalis 1, 5
- Methicillin-sensitive Staphylococcus aureus 2
- Many β-lactamase-producing E. coli, Klebsiella, Proteus (in urine) 8
Resistance Patterns
High-dose formulations achieve middle ear fluid and tissue concentrations adequate to overcome penicillin-resistant S. pneumoniae based on PK/PD modeling. 6, 5 The predicted clinical efficacy of high-dose regimens is 90-92% in both adults and children with acute bacterial rhinosinusitis. 1, 2
Using standard doses when high-dose therapy is indicated leads to treatment failure with resistant organisms. 6
Administration and Adverse Effects
Administration Guidelines
- Take at the start of meals to minimize gastrointestinal intolerance and enhance clavulanate absorption 7
- Shake oral suspensions well before each use 7
- Switch from IV to oral as soon as clinically appropriate 2
Common Adverse Effects
Diarrhea is the most common side effect, occurring more frequently with higher clavulanate doses. 3, 9 Other effects include: 6, 9
- Nausea and vomiting (reduced by taking with food)
- Rash
- Abdominal discomfort
The high-dose 14:1 ratio formulation (90/6.4 mg/kg) significantly reduces diarrhea incidence compared to older formulations while maintaining efficacy. 6, 3
Hepatic Considerations
Dose hepatically impaired patients with caution and monitor liver function regularly. 7
Common Pitfalls to Avoid
Prescribing antibiotics for viral URTIs: Most upper respiratory infections are viral and do not benefit from antibiotics. 6 Ensure criteria for bacterial infection are met before prescribing.
Underdosing pediatric patients: An 80 mg dose for a 5-year-old is grossly inadequate—the correct dose is approximately 375-450 mg total daily (based on weight). 6
Substituting non-interchangeable formulations: Different suspension concentrations have different clavulanate amounts and cannot be substituted. 7
Using standard-dose when high-dose is indicated: This leads to predictable treatment failure with resistant organisms. 6
Incorrect suspension concentration verification: Always verify whether you're using 125/31 vs 250/62 suspension before calculating volume. 6
Inadequate treatment duration: Stopping too early increases relapse risk. Complete the full course even if symptoms improve. 1, 6
Ignoring 72-hour reassessment: If no improvement after 72 hours, reevaluate diagnosis or switch antibiotics rather than continuing ineffective therapy. 1, 2