What is the recommended dosing regimen, contraindications, and alternative therapies for Augmentin (amoxicillin/clavulanate) in adults and children?

Augmentin (Amoxicillin-Clavulanate): Dosing, Contraindications, and Alternatives

Recommended Dosing Regimens

Adults

For most respiratory infections, prescribe amoxicillin-clavulanate 875 mg/125 mg twice daily for 5-7 days. 1

• Standard-dose regimen: 500 mg/125 mg three times daily or 875 mg/125 mg twice daily for uncomplicated infections 1
• High-dose regimen: 2000 mg amoxicillin/125 mg clavulanate twice daily for patients with risk factors 1

High-dose therapy is mandatory when any of these risk factors are present: 1

• Recent antibiotic use (past 4-6 weeks)
• Age >65 years
• Daycare exposure or close contact with treated individuals
• Moderate-to-severe symptoms
• Comorbidities or immunocompromised status
• Geographic areas with >10% penicillin-resistant Streptococcus pneumoniae
• Smokers or exposure to secondhand smoke
• Failed previous antibiotic therapy
• Frontal or sphenoidal sinusitis
• History of recurrent infections

• High-dose amoxicillin-clavulanate achieves 90-92% predicted clinical efficacy versus 83-88% for standard dosing 1
• Treatment duration is 5-7 days for acute bacterial sinusitis in adults, which is as effective as 10-day courses with fewer adverse effects 1

Pediatric Patients

For children with respiratory infections and risk factors, prescribe high-dose amoxicillin-clavulanate 90 mg/kg/day (amoxicillin component) with 6.4 mg/kg/day clavulanate, divided into 2 doses. 2, 1

• Standard-dose regimen: 45 mg/kg/day amoxicillin with 6.4 mg/kg/day clavulanate divided twice daily for uncomplicated infections 1
• High-dose regimen: 80-90 mg/kg/day amoxicillin with 6.4 mg/kg/day clavulanate divided twice daily for children with risk factors 2, 1
• Maximum daily dose: 4000 mg amoxicillin 1

High-dose pediatric therapy is required for: 2, 1

• Age <2 years
• Daycare attendance
• Recent antibiotic treatment (past 30 days)
• Concurrent purulent conjunctivitis
• Geographic areas with >10% penicillin-resistant S. pneumoniae
• Incomplete Haemophilus influenzae type b vaccination
• Moderate-to-severe illness

• Treatment duration is 10-14 days for children with acute bacterial sinusitis or acute otitis media 1, 3
• The 14:1 ratio of amoxicillin to clavulanate in high-dose formulations causes less diarrhea than other preparations 2

Weight-Based Dosing Threshold

For patients weighing ≥40 kg, use adult dosing regimens rather than pediatric weight-based calculations. 1

Specific Indications

Acute Otitis Media (AOM)

• First-line treatment: High-dose amoxicillin-clavulanate (90 mg/kg/day amoxicillin with 6.4 mg/kg/day clavulanate) for children who have taken amoxicillin in the previous 30 days, those with concurrent conjunctivitis, or when coverage for β-lactamase-producing H. influenzae and M. catarrhalis is desired 2
• High-dose amoxicillin-clavulanate achieved 96% eradication of S. pneumoniae from middle ear at days 4-6 of therapy 2

Acute Bacterial Rhinosinusitis

• Adults: Amoxicillin-clavulanate 875 mg/125 mg twice daily for 5-7 days is preferred over amoxicillin alone 1
• Children: High-dose amoxicillin-clavulanate is strongly recommended as initial therapy 1

Non-Severe Pneumonia

• Children: First-line is amoxicillin 50 mg/kg in 2 divided doses for 5 days; escalate to high-dose amoxicillin-clavulanate if amoxicillin fails 1
• Adults: 625 mg three times daily or 875 mg/125 mg twice daily for 7-10 days 1

Bronchiectasis Exacerbations

• Dose: 625 mg (500 mg amoxicillin/125 mg clavulanate) three times daily for 14 days for β-lactamase-producing H. influenzae 1

Animal or Human Bite Infections

• Dose: 875 mg/125 mg twice daily 1

Clinical Reassessment Protocol

Reassess all patients at specific time points to prevent treatment failure and complications: 1

Adults

• At 3-5 days: If no clinical improvement, switch to high-dose amoxicillin-clavulanate or a respiratory fluoroquinolone 1
• At 7 days: Persistent or worsening symptoms require diagnostic reconsideration, possible CT imaging, and ENT referral 1

Children

• At 72 hours: Lack of improvement or clinical worsening warrants escalation to high-dose amoxicillin-clavulanate 1
• If no improvement after 72 hours on high-dose therapy, consider changing antibiotics or reevaluating with cultures, CT, or endoscopy 1

Contraindications and Precautions

Absolute Contraindications

• History of serious hypersensitivity (anaphylaxis, Stevens-Johnson syndrome) to amoxicillin, clavulanate, or any β-lactam antibiotic 1
• History of cholestatic jaundice or hepatic dysfunction associated with prior amoxicillin-clavulanate use 1

Relative Contraindications and Warnings

• Renal dysfunction: Seizures may occur with high doses or impaired renal function; dose adjustment required 4
• Infectious mononucleosis: High risk of maculopapular rash with amoxicillin 1

Critical Prescribing Pitfalls

Avoid antibiotics entirely for symptom duration <10 days unless severe features are present (fever ≥39°C with purulent nasal discharge for ≥3 consecutive days), as 98-99.5% of acute rhinosinusitis cases are viral. 1

• Minimum treatment duration is ≥5 days for adults and ≥10 days for children to reduce relapse risk 1
• Do not routinely cover S. aureus (including MRSA) during initial empiric therapy of acute bacterial rhinosinusitis 1

Alternative Therapies

For Penicillin Allergy

Adults: 1

• Doxycycline (preferred for non-severe allergy)
• Respiratory fluoroquinolones (levofloxacin or moxifloxacin)

Children with non-type I penicillin allergy: 1

• Clindamycin plus a third-generation oral cephalosporin (cefdinir, cefuroxime, or cefpodoxime)
• These cephalosporins have distinct chemical structures and are highly unlikely to cross-react with penicillin allergy 2

For Treatment Failure

After 48-72 hours of initial antibiotic failure: 2

• First escalation: Ceftriaxone 50 mg/kg IM or IV daily for 3 days
• Second-line: Clindamycin 30-40 mg/kg/day in 3 divided doses, with or without third-generation cephalosporin
• Refractory cases: Consider tympanocentesis/drainage or infectious disease consultation for multidrug-resistant bacteria 2

Parenteral Alternative

Ceftriaxone 1 gram IM or IV daily for 5 days is recommended for patients who cannot tolerate oral medication or require initial parenteral therapy. 1

Adjunctive Therapies to Enhance Outcomes

Intranasal corticosteroids (mometasone, fluticasone, or budesonide) twice daily reduce mucosal inflammation and speed symptom resolution; this is supported by strong evidence from multiple randomized controlled trials. 1

• Saline nasal irrigation 2-3 times daily provides symptomatic relief and enhances mucus clearance 1
• Analgesics (acetaminophen or ibuprofen) for pain and fever control 1

Antimicrobial Spectrum and Resistance Considerations

Amoxicillin-clavulanate provides coverage for: 2, 1

• Penicillin-susceptible and -intermediate S. pneumoniae
• β-lactamase-producing H. influenzae (58-82% of isolates produce β-lactamase)
• β-lactamase-producing M. catarrhalis
• β-lactamase-producing S. aureus (MSSA)

• Current data show 58-82% of H. influenzae isolates are susceptible to regular- and high-dose amoxicillin, representing a significant decrease in β-lactamase-producing strains 2
• High-dose formulations overcome penicillin resistance in S. pneumoniae because resistance is relative and can be surmounted with higher concentrations 3
• Activity against β-lactamase-producing H. influenzae is limited with amoxicillin alone; clavulanate is essential for coverage 3