What is the appropriate use and dosage of Co-amoxiclav (amoxicillin/clavulanic acid) for a patient?

Co-amoxiclav (Amoxicillin/Clavulanate) Dosing and Clinical Use

Co-amoxiclav is a first-line antibiotic for respiratory tract infections, with standard adult dosing of 875 mg/125 mg twice daily or 625 mg three times daily, escalating to high-dose 2000 mg/125 mg twice daily when antibiotic resistance is likely or in patients with specific risk factors. 1

Adult Dosing Regimens

Standard-Dose Therapy

• For mild to moderate respiratory infections without resistance risk factors: 625 mg (500 mg amoxicillin/125 mg clavulanate) three times daily or 875 mg/125 mg twice daily for 7-10 days 1, 2
• For non-severe community-acquired pneumonia: 625 mg three times daily for 7-10 days 1
• For COPD exacerbations (Anthonisen type I or type II with purulence): Co-amoxiclav is the recommended first-line agent when no Pseudomonas risk factors are present 3

High-Dose Therapy (2000 mg/125 mg twice daily)

This regimen achieves adequate serum concentrations to eradicate penicillin-resistant Streptococcus pneumoniae with MICs up to 4-8 mg/L and should be used in the following situations: 1, 4

• Recent antibiotic use within the past 4-6 weeks 3, 1
• Recent hospitalization or close contact with healthcare environments 3, 1
• Previous antibiotic therapy failure 1, 4
• High prevalence of resistant bacteria in the community (>10% penicillin-resistant S. pneumoniae) 1, 2
• Moderate to severe infections including frontal or sphenoidal sinusitis 1, 4
• Age >65 years 1, 4
• Comorbidities: diabetes mellitus, chronic heart/lung/liver/kidney disease 1, 4
• Immunocompromised status 1, 4
• Smoking or exposure to smokers 2

Intravenous Therapy

• For severe pneumonia requiring hospitalization: 1.2 g three times daily IV, switching to oral formulation (625 mg three times daily) as soon as clinically appropriate 1, 2

Pediatric Dosing

Standard-Dose Regimen

• For uncomplicated infections: 45 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate divided into 2 doses 1, 2
• Alternative dosing: 25 mg/kg/day every 12 hours or 20 mg/kg/day every 8 hours for less severe infections 1

High-Dose Regimen (90 mg/kg/day amoxicillin with 6.4 mg/kg/day clavulanate in 2 divided doses)

Indicated for children with the following risk factors: 3, 1, 2

• Age <2 years 2
• Daycare attendance 2
• Recent antibiotic use within the previous 30 days 2
• Areas with high prevalence (>10%) of penicillin-resistant S. pneumoniae 3, 2
• Concurrent conjunctivitis (otitis-conjunctivitis syndrome) 1, 2
• Pneumonia not responding to amoxicillin alone 2

The 14:1 ratio formulation (90 mg/6.4 mg per kg) causes less diarrhea than other amoxicillin-clavulanate preparations. 2

Infection-Specific Treatment Duration

• Acute bacterial rhinosinusitis in adults: 5-7 days 1, 4, 2
• Acute bacterial rhinosinusitis in children: 10-14 days (longer than adults) 1, 2
• Community-acquired pneumonia: 7-10 days, may extend to 14 days based on clinical response 1, 4
• COPD exacerbations: 7-10 days 3
• Bronchiectasis exacerbations: 14 days 2
• Uncomplicated urinary tract infections: 3-7 days 1, 4

Specific Clinical Indications

Respiratory Infections

• Beta-lactamase producing Haemophilus influenzae: Co-amoxiclav 625 mg three times daily PO or 1.2 g three times daily IV 3
• COPD exacerbations requiring hospitalization: Co-amoxiclav is recommended as first-line therapy; levofloxacin and moxifloxacin are alternatives 3
• Bronchiectasis exacerbations: Obtain sputum culture before starting treatment; stratify patients by Pseudomonas risk 3

Urinary Tract Infections

• Co-amoxiclav is a first-choice option for lower urinary tract infections 4
• Duration: 3-7 days for uncomplicated UTIs 1, 4

Animal or Human Bite Infections

• 875 mg/125 mg twice daily 2

Critical Clinical Decision Points

When to Escalate to High-Dose Therapy

Use the 2000 mg/125 mg twice daily formulation when ANY of the following are present: 1, 4

• Recent antibiotic exposure (last 4-6 weeks)
• Age >65 years
• Significant comorbidities
• Geographic area with >10% penicillin-resistant S. pneumoniae
• Moderate-severe infection severity

Evaluation of Treatment Response

• Assess clinical response within 48-72 hours of initiating therapy 1, 4
• If no improvement or worsening after 72 hours: Switch to alternate antimicrobial therapy or reevaluate the patient with cultures, CT imaging, or endoscopy 3, 4, 2
• Consider limitations in coverage of the initial agent when changing antibiotics 3

Route of Administration

• Switch from IV to oral as soon as clinically appropriate, typically by day 3 if patient is clinically stable 3, 1, 2

Common Pitfalls and Caveats

Underdosing in High-Resistance Areas

• In areas with >10% penicillin-resistant S. pneumoniae, always use high-dose formulations (2000 mg/125 mg twice daily for adults or 90 mg/kg/day for children) 1, 4
• Standard dosing may result in clinical failure against resistant pathogens 1

Pseudomonas Risk in COPD/Bronchiectasis

• Do not use co-amoxiclav when ≥2 Pseudomonas risk factors are present: 3
  • Recent hospitalization
  • Frequent antibiotic courses (>4 per year) or recent use (last 3 months)
  • Severe disease (FEV1 <30%)
  • Oral steroid use (>10 mg prednisolone daily in last 2 weeks)
• For Pseudomonas risk: Use ciprofloxacin, levofloxacin 750 mg/24h, or IV beta-lactam with antipseudomonal activity 3

Inappropriate Use

• Do not use for prophylaxis in chronic bronchitis or COPD 3
• Do not routinely cover for MRSA during initial empiric therapy of acute bacterial rhinosinusitis 2

Tolerability

• Clavulanate dose is restricted to 125 mg in adult formulations due to tolerability issues 5
• Most common adverse effects are mild-to-moderate gastrointestinal symptoms 6, 7

Resistance Considerations

• Clavulanate has minimal role in respiratory infections; its primary benefit is coverage of beta-lactamase-producing organisms 5
• Empirical overuse may select resistance in Gram-negative pathogens, particularly ESBL-producing organisms 5