What are the recommended amoxicillin dosing regimens for acute bacterial rhinosinusitis, acute otitis media, and streptococcal pharyngitis in adults and children, and how should the dose be modified in patients with renal impairment or penicillin allergy?

Amoxicillin Dosing Guidelines

Adult Dosing for Respiratory Infections

For acute bacterial rhinosinusitis in adults, amoxicillin-clavulanate 875 mg/125 mg twice daily for 5–10 days is the preferred first-line regimen, providing 90–92% predicted clinical efficacy against the major pathogens. 1

• Standard adult dose: 500 mg twice daily for mild disease or 875 mg twice daily for moderate disease, continued for 5–10 days. 1
• High-dose regimen: 2 g amoxicillin/125 mg clavulanate twice daily is indicated when any of the following risk factors are present: recent antibiotic use (past 4–6 weeks), age >65 years, daycare exposure, moderate-to-severe symptoms, comorbidities (diabetes, chronic cardiac/hepatic/renal disease), immunocompromised state, or smoking/exposure to smoke. 1
• Treatment duration: Continue for 5–10 days or until symptom-free for 7 consecutive days (typically 10–14 days total); recent evidence supports shorter 5–7 day courses with comparable efficacy and fewer adverse effects. 1

When to Use Plain Amoxicillin vs. Amoxicillin-Clavulanate

• Plain amoxicillin may be used only for mild disease in patients who have not received antibiotics in the preceding 4–6 weeks; otherwise, amoxicillin-clavulanate is preferred due to increasing prevalence of β-lactamase-producing organisms (30–40% of H. influenzae and 90–100% of M. catarrhalis). 1

Pediatric Dosing for Respiratory Infections

For children with acute bacterial rhinosinusitis, high-dose amoxicillin-clavulanate (90 mg/kg/day amoxicillin component + 6.4 mg/kg/day clavulanate divided twice daily) is strongly recommended as first-line therapy. 1

• Standard pediatric dose: 45 mg/kg/day amoxicillin divided twice daily for uncomplicated infections in children ≥2 years without risk factors. 1, 2
• High-dose pediatric regimen: 80–90 mg/kg/day amoxicillin (maximum 4 g/day) divided twice daily when any of the following risk factors are present: age <2 years, daycare attendance, recent antibiotic use (past 30 days), regional prevalence of penicillin-resistant *S. pneumoniae* >10%, moderate-to-severe illness, or concurrent purulent otitis media. 1, 2
• Treatment duration: Minimum 10–14 days for children (longer than adult courses), or continue for 7 days after becoming symptom-free. 1, 2
• Maximum daily dose: Do not exceed 4,000 mg/day of amoxicillin regardless of weight. 1, 2

Pediatric Dosing for Specific Infections

• Community-acquired pneumonia: 90 mg/kg/day amoxicillin divided twice daily for presumed bacterial pneumonia in children ≥3 months, ensuring coverage of penicillin-resistant S. pneumoniae. 2
• Group A streptococcal pharyngitis: 50–75 mg/kg/day divided twice daily (maximum 1,000 mg per dose) for 10 days; an alternative once-daily regimen of 50 mg/kg/day (capped at 1,000 mg) is equally effective and improves adherence. 2
• Acute otitis media: Use high-dose amoxicillin-clavulanate (90 mg/kg/day amoxicillin component) for children who have received antibiotics within the past 4–6 weeks, to cover β-lactamase-producing organisms. 1

Streptococcal Pharyngitis (All Ages)

• Pediatric dosing: 50–75 mg/kg/day divided twice daily for 10 days, with a maximum single dose of 1,000 mg. 2
• Adult dosing: Follow the same mg/kg calculation but cap each dose at 1,000 mg. 2
• Treatment duration: Complete the full 10-day course regardless of symptom improvement to prevent acute rheumatic fever; fever typically resolves within 3–4 days, but the full course is essential. 2
• Antibiotic initiation timing: Therapy may be started up to 9 days after symptom onset and still effectively prevent acute rheumatic fever. 2

Alternatives for Penicillin Allergy

Non-Severe (Non-Type I) Penicillin Allergy

• Second- or third-generation cephalosporins (cefuroxime-axetil, cefpodoxime-proxetil, cefdinir, cefprozil) for 10 days are appropriate; cross-reactivity with penicillin is negligible. 1, 3

Severe (Type I/Anaphylactic) Penicillin Allergy

• Respiratory fluoroquinolones are the treatment of choice: levofloxacin 500 mg once daily for 10–14 days or moxifloxacin 400 mg once daily for 10 days, providing 90–92% predicted efficacy against multidrug-resistant pathogens. 1, 3
• Pediatric alternatives for severe allergy: Clindamycin 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days, or azithromycin 12 mg/kg once daily (maximum 500 mg) for 5 days; use cautiously due to potential resistance. 2

Suboptimal Alternative

• Doxycycline 100 mg once daily for 10 days yields only 77–81% predicted efficacy with a 20–25% bacteriologic failure rate due to limited H. influenzae coverage; reserve only when fluoroquinolones and cephalosporins are contraindicated. 1, 3

Renal Impairment Dosing

• Creatinine clearance 10–30 mL/min: Reduce amoxicillin-clavulanate to 875 mg/125 mg once daily. 3
• Creatinine clearance <10 mL/min: Administer 875 mg/125 mg every 24 hours or consider alternative treatments. 3
• Hemodialysis patients: Prescribe amoxicillin-clavulanate 875 mg/125 mg once daily administered immediately after each dialysis session (typically three times per week) to maintain therapeutic drug levels throughout the interdialytic interval. 3

Reassessment and Treatment Failure Protocol

• Reassess at 3–5 days: If no clinical improvement (persistent purulent drainage, unchanged facial pain, or worsening), switch immediately to high-dose amoxicillin-clavulanate or a respiratory fluoroquinolone. 1, 3
• Pediatric reassessment: Evaluate at 72 hours; lack of improvement or clinical worsening warrants escalation to high-dose amoxicillin-clavulanate. 1, 2
• Reassess at 7 days: Persistent or worsening symptoms require diagnostic reconsideration, exclusion of complications (orbital cellulitis, meningitis), and possible imaging or ENT referral. 1, 3

Critical Pitfalls to Avoid

• Do not prescribe antibiotics for symptoms <10 days unless severe features are present (fever ≥39°C with purulent discharge for ≥3 consecutive days); 98–99.5% of acute rhinosinusitis is viral and resolves spontaneously. 1, 3
• Ensure adequate treatment duration: Minimum 5 days for adults and 10 days for children to prevent relapse and resistance development. 1, 2
• Avoid macrolides (azithromycin, clarithromycin): Resistance rates exceed 20–25% for both S. pneumoniae and H. influenzae, making them unsuitable for sinusitis. 1, 3, 4
• Do not use first-generation cephalosporins (cephalexin): Inadequate coverage against H. influenzae because ~50% of strains produce β-lactamase. 3
• Gastrointestinal adverse effects: Amoxicillin-clavulanate causes diarrhea in 40–43% of patients (severe diarrhea in 7–8%); the 14:1 ratio in high-dose formulations is less likely to cause diarrhea than other preparations. 1, 5

Essential Adjunctive Therapies (Add to All Patients)

• Intranasal corticosteroids (mometasone, fluticasone, budesonide) twice daily significantly reduce mucosal inflammation and accelerate symptom resolution; supported by strong evidence from multiple randomized controlled trials. 1, 3
• Saline nasal irrigation 2–3 times daily provides symptomatic relief and aids mucus clearance. 1, 3
• Analgesics (acetaminophen or ibuprofen) for pain and fever control. 1, 3

Referral to Otolaryngology

Refer immediately for any of the following:

• No improvement after 7 days of appropriate second-line antibiotic therapy. 1, 3
• Worsening symptoms at any point during treatment. 1, 3
• Suspected complications (orbital cellulitis, meningitis, intracranial abscess, severe headache, visual changes, periorbital swelling, altered mental status). 1, 3
• Recurrent sinusitis (≥3 episodes per year) requiring evaluation for underlying allergic rhinitis, immunodeficiency, or anatomic abnormalities. 1, 3