What is the first‑line antibiotic for uncomplicated acute bacterial sinusitis in a healthy adult without a penicillin allergy, and what alternatives are appropriate for a severe penicillin allergy?

First-Line Antibiotic for Uncomplicated Acute Bacterial Sinusitis

Amoxicillin-clavulanate 875 mg/125 mg twice daily for 5–10 days is the preferred first-line antibiotic for otherwise healthy adults without penicillin allergy, providing 90–92% predicted clinical efficacy against the major sinusitis pathogens. 1, 2

Confirming the Diagnosis Before Prescribing

Before initiating antibiotics, confirm that the patient meets at least one of three diagnostic patterns for acute bacterial rhinosinusitis (ABRS):

• Persistent symptoms ≥ 10 days with purulent nasal discharge plus either nasal obstruction or facial pain/pressure/fullness. 1
• Severe symptoms ≥ 3–4 consecutive days with fever ≥ 39°C, purulent nasal discharge, and facial pain. 1
• "Double sickening": initial improvement from a viral upper respiratory infection followed by worsening symptoms within 10 days. 1

Critical context: Approximately 98–99.5% of acute rhinosinusitis cases are viral and resolve spontaneously within 7–10 days without antibiotics. 1 Do not prescribe antibiotics for symptoms lasting < 10 days unless the severe criteria above are met. 1

First-Line Regimen for Non-Allergic Patients

• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily for 5–10 days (or until symptom-free for 7 consecutive days, typically 10–14 days total). 1, 2
• The clavulanate component is essential because 30–40% of Haemophilus influenzae and 90–100% of Moraxella catarrhalis produce β-lactamase. 1
• Recent evidence supports shorter 5–7 day courses with comparable efficacy and fewer adverse effects. 1, 3

High-Dose Regimen for Specific Risk Factors

Use high-dose amoxicillin-clavulanate 2 g/125 mg twice daily when any of the following are present: 1, 2

• Recent antibiotic use (within past 4–6 weeks)
• Age > 65 years
• Daycare exposure
• Moderate-to-severe symptoms
• Comorbidities (diabetes, chronic cardiac/hepatic/renal disease)
• Immunocompromised state

Alternatives for Penicillin-Allergic Patients

Non-Severe (Non-Type I) Penicillin Allergy

For patients with mild reactions (e.g., rash), second- or third-generation cephalosporins are preferred because cross-reactivity is negligible (< 1%). 1, 4

• Cefuroxime-axetil 250–500 mg twice daily for 10 days 4
• Cefpodoxime-proxetil 200 mg twice daily for 10 days 4
• Cefdinir 300 mg twice daily for 10 days 4

Severe (Type I/Anaphylactic) Penicillin Allergy

For patients with documented anaphylaxis, angioedema, urticaria, or bronchospasm, respiratory fluoroquinolones are the treatment of choice: 1, 4

• Levofloxacin 500 mg once daily for 10–14 days 1, 4
• Moxifloxacin 400 mg once daily for 10 days 1, 4

Both provide 90–92% predicted efficacy against multidrug-resistant Streptococcus pneumoniae and β-lactamase-producing organisms. 1, 4

Reserve fluoroquinolones for documented severe β-lactam allergy or treatment failure to limit resistance development. 1, 4

Antibiotics to Avoid

• Macrolides (azithromycin, clarithromycin): 20–25% resistance rates in S. pneumoniae and H. influenzae make them unsuitable. 1, 4
• Trimethoprim-sulfamethoxazole: 50% resistance in S. pneumoniae and 27% in H. influenzae. 1, 4
• First-generation cephalosporins (cephalexin): inadequate coverage because ~50% of H. influenzae strains produce β-lactamase. 1

Essential Adjunctive Therapies (Add to All Patients)

• Intranasal corticosteroids (mometasone, fluticasone, or budesonide) twice daily significantly reduce mucosal inflammation and accelerate symptom resolution—supported by strong evidence from multiple randomized controlled trials. 1, 2, 4
• Saline nasal irrigation 2–3 times daily provides symptomatic relief and aids mucus clearance. 1, 4
• Analgesics (acetaminophen or ibuprofen) for pain and fever control. 1

Monitoring and Reassessment

• Reassess at 3–5 days: If no clinical improvement (persistent purulent drainage, unchanged facial pain, or worsening), switch to high-dose amoxicillin-clavulanate or a respiratory fluoroquinolone. 1, 2
• Reassess at 7 days: Persistent or worsening symptoms warrant confirmation of diagnosis, exclusion of complications (orbital cellulitis, meningitis), and consideration of imaging or ENT referral. 1

Expected timeline: Noticeable improvement should occur within 3–5 days, with complete resolution by 10–14 days. 1

Watchful Waiting Option

For uncomplicated cases with reliable follow-up, initial observation without antibiotics is appropriate. 1 Initiate antibiotics only if no improvement by day 7 or if symptoms worsen at any time. 1 The number needed to treat (NNT) with antibiotics is 10–15 to achieve one additional cure. 1

Critical Pitfalls to Avoid

• Do not prescribe antibiotics for symptoms < 10 days unless severe features (fever ≥ 39°C with purulent discharge for ≥ 3 consecutive days) are present. 1
• Do not obtain routine imaging (X-ray or CT) for uncomplicated ABRS; up to 87% of viral upper respiratory infections show sinus abnormalities on imaging. 1
• Ensure adequate treatment duration (≥ 5 days for adults) to prevent relapse. 1
• Gastrointestinal adverse effects with amoxicillin-clavulanate are common: diarrhea in 40–43% of patients, severe diarrhea in 7–8%. 1

Referral to Otolaryngology

Refer immediately if any of the following occur: 1, 4

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