What are the indications, dosing regimens, contraindications, adverse effects, renal dose adjustments, and alternative therapies for Augmentin (amoxicillin/clavulanate)?

Augmentin (Amoxicillin-Clavulanate): Clinical Guide

Primary Indications

Augmentin is first-line therapy for acute bacterial rhinosinusitis, acute otitis media, community-acquired pneumonia, and animal bite wounds when β-lactamase-producing organisms or drug-resistant Streptococcus pneumoniae are suspected. 1

Respiratory Infections

• Acute bacterial rhinosinusitis (adults): Use when patients have recent antibiotic exposure (past 4-6 weeks), age >65, moderate-to-severe symptoms, or comorbidities 2
• Acute otitis media (children): Indicated for children with recent antibiotic use within 30 days, daycare attendance, concurrent conjunctivitis, or age <2 years 1
• Community-acquired pneumonia: Effective against β-lactamase-producing Haemophilus influenzae, Moraxella catarrhalis, and penicillin-intermediate S. pneumoniae 3

Other Infections

• Animal/human bite wounds: First-line for coverage of Pasteurella multocida, Staphylococcus aureus, Streptococcus species, Eikenella corrodens, and anaerobes 4
• Urinary tract infections: Effective for multiply-resistant organisms producing β-lactamase 5

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Dosing Regimens

Adults

Standard dose: 875 mg/125 mg twice daily for 5-7 days for uncomplicated respiratory infections 2

High-dose regimen: 2000 mg/125 mg twice daily for patients with:

• Recent antibiotic use (past 4-6 weeks) 2
• Age >65 years 2
• Moderate-to-severe infection 2
• Areas with >10% penicillin-resistant S. pneumoniae 2
• Immunocompromised status 2
• Frontal or sphenoidal sinusitis 1

Alternative standard dose: 500 mg/125 mg three times daily for 7-14 days for bronchiectasis or severe respiratory infections 2

Bite wounds: 875 mg/125 mg twice daily for 5-7 days (extend to 10-14 days for bone/joint involvement) 4

Pediatric Patients

High-dose (first-line for most infections): 90 mg/kg/day amoxicillin component + 6.4 mg/kg/day clavulanate, divided twice daily 1, 2

Standard dose (uncomplicated cases only): 45 mg/kg/day amoxicillin component + 6.4 mg/kg/day clavulanate, divided twice daily 2

Maximum daily dose: 4000 mg amoxicillin 2

Children ≥40 kg: Use adult dosing (875 mg/125 mg twice daily) 2, 4

Duration:

• Sinusitis: 10-14 days 1, 2
• Otitis media: 10 days 1
• Pneumonia: 5 days 2
• Bite wounds: 5-7 days (uncomplicated), 10-14 days (severe) 4

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Key Prescribing Algorithm

When to Use High-Dose in Children

Use 90 mg/kg/day formulation if any of the following apply:

• Age <2 years 2
• Daycare attendance 2
• Recent antibiotic use (past 30 days) 1, 2
• Concurrent purulent conjunctivitis 1
• Regional penicillin-resistant S. pneumoniae prevalence >10% 2
• Moderate-to-severe illness 2
• Treatment failure with amoxicillin alone 1

When to Use High-Dose in Adults

Use 2000 mg/125 mg twice daily if any of the following apply:

• Antibiotic use in past 4-6 weeks 2
• Age >65 years 2
• Smoker or smoke exposure 2
• Comorbidities (diabetes, heart/lung/liver/renal disease) 2
• Immunocompromised 2
• Moderate-to-severe symptoms 2

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Contraindications

Absolute contraindications:

• History of cholestatic jaundice or hepatic dysfunction with prior amoxicillin-clavulanate use 6
• Immediate (Type I) hypersensitivity to penicillins 1

Relative contraindications:

• Infectious mononucleosis (high risk of rash) 6
• Severe renal impairment without dose adjustment 6

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Renal Dose Adjustments

Creatinine clearance 10-30 mL/min:

• Adults: 500 mg/125 mg every 12 hours or 250 mg/125 mg every 12 hours for less severe infections 2

Creatinine clearance <10 mL/min:

• Adults: 500 mg/125 mg every 24 hours or 250 mg/125 mg every 24 hours 2

Hemodialysis:

• 500 mg/125 mg every 24 hours with additional dose during and after dialysis 2

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Adverse Effects

Most common (dose-related):

• Diarrhea (10-15% with three-times-daily dosing; reduced to 3-5% with twice-daily dosing) 7, 6
• Nausea and vomiting (2-5%) 6, 8
• Abdominal discomfort 6

The 14:1 amoxicillin-to-clavulanate ratio (high-dose formulation) significantly reduces diarrhea compared to older 7:1 or 4:1 ratios. 1, 7

Less common:

• Skin rash (1-3%) 6
• Candidal overgrowth 6
• Reversible hepatotoxicity (rare, monitor if treatment >14 days) 6

Minimize gastrointestinal effects: Administer with food 6, 8

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Clinical Reassessment Protocol

Adults

• At 3-5 days: If no improvement, switch to respiratory fluoroquinolone (levofloxacin or moxifloxacin) 2
• At 7 days: Persistent symptoms require CT imaging, endoscopy, or ENT referral 2

Children

• At 72 hours: Lack of improvement warrants escalation to high-dose amoxicillin-clavulanate (if not already used) or ceftriaxone 50 mg/kg IM/IV daily for 3 days 1
• After second antibiotic failure: Perform tympanocentesis or refer to ENT 1

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Alternative Therapies

Penicillin Allergy (Non-Type I)

• Adults: Respiratory fluoroquinolone (levofloxacin 500-750 mg daily or moxifloxacin 400 mg daily) 1, 2
• Children: Cefdinir 14 mg/kg/day, cefuroxime 30 mg/kg/day, or cefpodoxime 10 mg/kg/day (cross-reactivity <1% with third-generation cephalosporins) 1

Penicillin Allergy (Type I/Anaphylactic)

• Adults: Respiratory fluoroquinolone 1, 2
• Children: Clindamycin 30-40 mg/kg/day plus third-generation cephalosporin (if no cephalosporin allergy) 1

Treatment Failure

• Adults: Levofloxacin 750 mg daily or moxifloxacin 400 mg daily 2
• Children: Ceftriaxone 50 mg/kg IM/IV daily for 3 days 1

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Critical Pitfalls to Avoid

1. Do not prescribe antibiotics for viral rhinosinusitis: 98-99.5% of cases with symptoms <10 days are viral; antibiotics are indicated only if symptoms persist ≥10 days or worsen after initial improvement 2

2. Do not use standard-dose amoxicillin-clavulanate in high-risk patients: Treatment failure rates reach 20-25% when risk factors for resistance are present 2

3. Do not use inadequate treatment duration: Minimum 5 days for adults and 10 days for children to prevent relapse 2

4. Avoid first-generation cephalosporins, macrolides, or clindamycin monotherapy for bite wounds: These lack adequate coverage for Pasteurella multocida 4

5. Do not use amoxicillin-clavulanate for MDR-TB: Associated with increased mortality (aOR 1.7) and decreased treatment success (aOR 0.6); use only when providing clavulanate for carbapenem therapy 1

6. Verify weight-based dosing threshold: Children ≥40 kg require adult dosing, not pediatric weight-based calculations 2

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Special Populations

Pregnancy: Category B; generally safe but use only when clearly needed 6

Breastfeeding: Compatible; minimal transfer to breast milk 6

Asplenia/hyposplenia: Mandatory 5-day prophylaxis for bite wounds due to severe sepsis risk 4

Immunocompromised: Always use high-dose regimens 2