Amoxicillin Dosing for Sinusitis
For acute bacterial sinusitis in adults, prescribe amoxicillin 500 mg twice daily for 5-10 days as first-line therapy, or amoxicillin-clavulanate 875/125 mg twice daily if risk factors for resistance are present. 1, 2
Standard First-Line Treatment
Amoxicillin 500 mg orally twice daily is the recommended first-line antibiotic for uncomplicated acute bacterial rhinosinusitis (ABRS) in adults due to its safety, efficacy, low cost, and narrow microbiologic spectrum. 1
For more severe infections, increase to amoxicillin 875 mg twice daily. 3
Treatment duration should be 5-10 days, with most guidelines recommending continuation until the patient has been symptom-free for 7 days (typically 10-14 days total). 1, 2, 3
Shorter 5-7 day courses demonstrate comparable efficacy with fewer adverse effects compared to 10-14 day regimens. 3
When to Escalate to Amoxicillin-Clavulanate
Switch to amoxicillin-clavulanate 875/125 mg twice daily if any of these risk factors are present: 1
Resistance Risk Factors:
- Antibiotic use within the past month
- Recent hospitalization or close contact with healthcare environments
- Failure of prior antibiotic therapy
- Close contact with daycare facilities
- Smoking or household smoker exposure
- Geographic areas with high prevalence of resistant bacteria (>10% penicillin-nonsusceptible S. pneumoniae)
Severity Indicators:
- Moderate to severe symptoms at presentation
- Protracted symptoms (>10 days without improvement)
- Frontal or sphenoidal sinusitis
- History of recurrent ABRS (≥3 episodes per year)
- Fever ≥39°C (102°F) with systemic toxicity
Patient Factors:
- Age >65 years
- Immunocompromised status
- Comorbidities (diabetes, chronic cardiac/hepatic/renal disease)
High-Dose Regimens for Resistant Organisms
For patients at high risk of penicillin-nonsusceptible S. pneumoniae, use high-dose amoxicillin-clavulanate 2000 mg/125 mg orally twice daily. 1
Important caveat: Recent randomized trials show conflicting evidence on high-dose efficacy. One trial found immediate-release high-dose (1750 mg twice daily) provided 18% greater improvement at day 3 compared to standard dose, but with increased severe diarrhea (15.8% vs 4.8%). 4 However, a subsequent larger trial found no benefit of high-dose over standard-dose, with similar diarrhea rates. 5
Clinical recommendation: Reserve high-dose regimens for patients with multiple resistance risk factors rather than routine use, given the increased adverse effect burden without consistent efficacy benefit. 4, 5
Penicillin-Allergic Patients
For documented penicillin allergy: 1, 3
Non-type I hypersensitivity: Second-generation cephalosporins (cefuroxime) or third-generation cephalosporins (cefpodoxime, cefdinir) are appropriate alternatives, as cross-reactivity risk is negligible. 3
Type I hypersensitivity (anaphylaxis): Use doxycycline or respiratory fluoroquinolones (levofloxacin 500 mg daily or moxifloxacin 400 mg daily). 1
Avoid macrolides (azithromycin, clarithromycin) due to >40% resistance rates of S. pneumoniae in the United States. 1, 3
Avoid trimethoprim-sulfamethoxazole due to 50% resistance in S. pneumoniae and 27% in H. influenzae. 1
Treatment Failure Protocol
Reassess at 3 days if no improvement or worsening occurs. 2, 3
If initial amoxicillin fails, switch to amoxicillin-clavulanate 875/125 mg twice daily. 3
If amoxicillin-clavulanate fails, escalate to respiratory fluoroquinolone (levofloxacin 500 mg daily or moxifloxacin 400 mg daily). 1, 3
Consider alternative diagnoses (viral infection, fungal sinusitis, anatomic obstruction) and potential complications if no response after 7 days. 6
Critical Pitfalls to Avoid
Do not treat viral upper respiratory infections with antibiotics—ABRS requires specific diagnostic criteria including purulent nasal discharge with unilateral predominance, facial pain/pressure with unilateral predominance, or symptoms persisting >10 days without improvement. 2, 6
Do not use fluoroquinolones as first-line therapy in non-allergic patients—reserve for treatment failures or complicated sinusitis to prevent resistance development. 1, 3
Ensure adequate treatment duration—stopping antibiotics when symptoms improve but before completing 5-7 days risks relapse (7.7% relapse rate within one month). 2, 7
Amoxicillin-clavulanate 875/125 mg twice daily is as effective as three-times-daily dosing with better compliance and similar adverse effect profiles. 8
Adjunctive Therapy
Intranasal corticosteroids (budesonide, mometasone) can be added as adjunctive therapy, though evidence shows modest benefit primarily in patients with less severe baseline symptoms. 3, 9
Short-term oral corticosteroids may help in acute hyperalgic sinusitis (severe facial pain) when combined with appropriate antibiotics. 3, 6
Supportive measures include adequate hydration, analgesics, warm facial compresses, and sleeping with head elevated. 3