What is the proper use and dosage of Amoxiclav (amoxicillin/clavulanic acid) for treating bacterial infections?

Amoxicillin-Clavulanate (Amoxiclav) Dosing and Use

For adults with respiratory tract infections, the standard dose is 500 mg/125 mg three times daily or 875 mg/125 mg twice daily, with high-dose therapy (2000 mg/125 mg twice daily) reserved for patients with risk factors for resistant pathogens. 1, 2, 3

Standard Adult Dosing

Mild to Moderate Infections

• 500 mg amoxicillin/125 mg clavulanate three times daily for 7-10 days is the standard regimen for most respiratory infections, skin/soft tissue infections, and uncomplicated urinary tract infections 1, 2, 3
• 875 mg/125 mg twice daily is an alternative dosing schedule that provides equivalent coverage and may improve compliance 1, 3
• Treatment should be taken at the start of meals to minimize gastrointestinal intolerance and enhance clavulanate absorption 4, 3

High-Dose Regimen for Resistant Pathogens

• 2000 mg amoxicillin/125 mg clavulanate twice daily is indicated when drug-resistant Streptococcus pneumoniae is suspected 1, 2
• This high-dose formulation achieves 90-92% predicted clinical efficacy against resistant strains 1

Risk Factors Requiring High-Dose Therapy

Use high-dose amoxicillin-clavulanate (2000 mg/125 mg twice daily) in adults with any of the following:

• Recent antibiotic use within the previous 4-6 weeks 1, 2
• Moderate to severe disease presentation 1, 2
• Geographic areas with >10% prevalence of penicillin-resistant S. pneumoniae 1
• Age over 65 years 1
• Immunocompromised status 1
• History of recurrent infections 1
• Failed previous antibiotic therapy 1
• Smokers or exposure to secondhand smoke 1
• Close contact with children in daycare 1

Pediatric Dosing

Standard Pediatric Regimen

• 45 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate divided into 2 doses for uncomplicated infections in children weighing less than 40 kg 1
• Children weighing 40 kg or more should follow adult dosing recommendations 3

High-Dose Pediatric Regimen

• 80-90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate divided into 2 doses for children with risk factors 1, 5
• Maximum daily dose is 4000 mg of amoxicillin 1
• The 14:1 ratio formulation (high-dose) causes less diarrhea than other amoxicillin-clavulanate preparations 1

Pediatric Risk Factors for High-Dose Therapy

• Age under 2 years 1
• Daycare attendance 1
• Recent antibiotic treatment within 30 days 1
• Concurrent conjunctivitis (suggests Moraxella catarrhalis) 1
• Pneumonia not responding to amoxicillin alone 1

Specific Indications and Duration

Acute Bacterial Sinusitis

• Adults: 500 mg/125 mg three times daily or 875 mg/125 mg twice daily for 5-7 days 1
• High-dose therapy (2000 mg/125 mg twice daily) for patients with risk factors 1
• 5-7 day courses are as effective as 10-day courses in most cases 1

Community-Acquired Pneumonia

• Non-severe: 625 mg three times daily or 875 mg/125 mg twice daily for 7-10 days 1
• Severe (requiring IV): 1.2 g three times daily IV, switching to oral as soon as clinically appropriate 1
• Pediatric non-severe pneumonia: First-line is amoxicillin 50 mg/kg in 2 divided doses; use high-dose amoxicillin-clavulanate if amoxicillin fails 1

Bronchiectasis Exacerbations

• 625 mg three times daily for 14 days when beta-lactamase producing Haemophilus influenzae is suspected 1

Animal or Human Bite Infections

• 875 mg/125 mg twice daily 1

Critical Dosing Considerations

Formulation Equivalency Warning

• Two 250 mg/125 mg tablets are NOT equivalent to one 500 mg/125 mg tablet because both contain the same amount of clavulanate (125 mg) 3
• Substituting two 250 mg tablets results in excessive clavulanate dosing and increased gastrointestinal side effects 2, 3
• Liquid formulations should not be used interchangeably with tablets without calculating equivalent amoxicillin doses 2

Renal Impairment Dosing

• GFR 10-30 mL/min: 500 mg or 250 mg every 12 hours 4, 3
• GFR <10 mL/min: 500 mg or 250 mg every 24 hours 4, 3
• Hemodialysis: 500 mg or 250 mg every 24 hours, with an additional dose during and at the end of dialysis 4, 3
• Patients with severe renal impairment (GFR <30 mL/min) should NOT receive the 875 mg dose 4, 3

Treatment Failure and Reassessment

• If no clinical improvement occurs after 72 hours, consider switching to a respiratory fluoroquinolone (levofloxacin or moxifloxacin) 1, 2
• Reevaluate the diagnosis with cultures, computed tomography, or endoscopy 1
• Consider alternative diagnoses or complications 2

Antimicrobial Spectrum

• Effective against beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis 1, 6
• Covers penicillin-susceptible and intermediate Streptococcus pneumoniae 6, 5
• High-dose formulations provide coverage for penicillin-resistant S. pneumoniae (MIC ≤2 mg/L in US, up to 4-8 mg/L with 2000 mg/125 mg formulation in Europe) 7, 6, 5
• Active against beta-lactamase-producing methicillin-susceptible Staphylococcus aureus (MSSA) 1

Common Pitfalls to Avoid

• Do not use amoxicillin-clavulanate empirically for MRSA coverage - routine coverage for S. aureus including MRSA is not recommended during initial empiric therapy 1
• Complete the full course even if symptoms improve early to prevent treatment failure and resistance development 2
• Monitor hepatic function in patients with hepatic impairment, as clavulanate can cause hepatotoxicity 3
• Reconstituted oral suspension expires after 14 days - refrigeration is preferable but not required 4