What is the first‑line antibiotic regimen for an otherwise healthy adult with acute bacterial sinusitis, and what are the appropriate alternatives for penicillin allergy or pregnancy?

First-Line Antibiotic for Acute Bacterial Sinusitis in Adults

Amoxicillin-clavulanate 875 mg/125 mg twice daily for 5–10 days is the preferred first-line antibiotic for otherwise healthy adults with acute bacterial sinusitis. 1, 2, 3

Diagnostic Confirmation Before Prescribing

Before initiating antibiotics, confirm the patient meets at least one of three diagnostic criteria for bacterial (not viral) sinusitis:

• Persistent symptoms ≥ 10 days without improvement—purulent nasal discharge plus either nasal obstruction or facial pain/pressure 1, 2, 3
• Severe symptoms ≥ 3–4 consecutive days—fever ≥ 39°C with purulent nasal discharge and facial pain 1, 2, 3
• "Double sickening"—initial improvement from a viral URI followed by worsening within 10 days 1, 2, 3

Critical context: Approximately 98–99.5% of acute rhinosinusitis is viral and resolves spontaneously within 7–10 days without antibiotics. 1 Do not prescribe antibiotics for symptoms < 10 days unless severe features (fever ≥ 39°C with purulent discharge for ≥ 3 consecutive days) are present. 1, 2, 3

Standard First-Line Regimen

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) provides 90–92% predicted clinical efficacy against the three major pathogens: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. 1, 2, 3

The clavulanate component is essential because 30–40% of H. influenzae and 90–100% of M. catarrhalis produce β-lactamase, rendering plain amoxicillin ineffective. 1, 2 Recent evidence supports shorter 5–7 day courses with comparable efficacy and fewer adverse effects. 1, 4, 5

High-Dose Regimen for Risk Factors

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

• Recent antibiotic use (within past 4–6 weeks) 1, 3
• Age > 65 years 1, 3
• Daycare exposure 1, 3
• Moderate-to-severe symptoms 1, 3
• Comorbidities (diabetes, chronic cardiac/hepatic/renal disease) 1, 3
• Immunocompromised state 1, 3

Note: A 2021 randomized trial found no additional benefit from high-dose versus standard-dose amoxicillin-clavulanate in adults with acute sinusitis, though severe diarrhea rates were similar (7% in both groups). 5 However, guidelines continue to recommend high-dose therapy for the risk factors above based on microbiologic rationale. 1, 3

Alternatives for Penicillin Allergy

Non-Severe (Non-Type I) Penicillin Allergy

For patients with mild rash or delayed reactions (not anaphylaxis):

• Second- or third-generation cephalosporins for 10 days 1, 2, 3
  • Cefuroxime-axetil 1, 3
  • Cefpodoxime-proxetil 1, 3
  • Cefdinir 1, 3
  • Cefprozil 1, 3

Cross-reactivity with penicillins is negligible (< 1%), making these safe alternatives. 1, 3 Recent evidence confirms the risk of serious allergic reactions to second- and third-generation cephalosporins in penicillin-allergic patients is almost nil. 3

Severe (Type I/Anaphylactic) Penicillin Allergy

For patients with anaphylaxis, urticaria, or angioedema to penicillin:

• Levofloxacin 500 mg once daily for 10–14 days 1, 2, 3
• Moxifloxacin 400 mg once daily for 10 days 1, 2, 3

Both respiratory fluoroquinolones provide 90–92% predicted efficacy against multidrug-resistant S. pneumoniae and β-lactamase-producing organisms. 1, 2, 3 Reserve fluoroquinolones for severe allergy or treatment failure to limit resistance development—do not use as routine first-line therapy. 1, 2, 3

Suboptimal Alternative

Doxycycline 100 mg once daily for 10 days is acceptable when cephalosporins and fluoroquinolones are contraindicated (e.g., pregnancy, tendon disorders), but offers lower efficacy (77–81%) with a 20–25% bacteriologic failure rate due to limited H. influenzae coverage. 1, 6

Special Considerations for Pregnancy

For pregnant patients with penicillin allergy:

• Second- or third-generation cephalosporins remain the preferred alternative (cross-reactivity negligible) 1, 3
• Avoid fluoroquinolones (contraindicated in pregnancy) 1
• Azithromycin is NOT recommended despite being pregnancy category B, because resistance rates exceed 20–25% for both S. pneumoniae and H. influenzae 1, 2

Antibiotics to Avoid

• Macrolides (azithromycin, clarithromycin): 20–25% resistance rates for S. pneumoniae and H. influenzae 1, 2, 3
• Trimethoprim-sulfamethoxazole: 50% resistance in S. pneumoniae, 27% in H. influenzae 1
• First-generation cephalosporins (cephalexin): Inadequate coverage because ~50% of H. influenzae 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, 3
• Saline nasal irrigation 2–3 times daily for symptomatic relief and mucus clearance 1, 2, 3
• Analgesics (acetaminophen or ibuprofen) for pain and fever control 1, 2, 3

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, 3
• 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, 2, 3

Expected timeline: Noticeable improvement within 3–5 days, complete resolution by 10–14 days or when symptom-free for 7 consecutive days. 1

Watchful Waiting Option

For uncomplicated cases with reliable follow-up, initial observation without antibiotics is appropriate. 1, 2, 3 Initiate antibiotics only if no improvement by day 7 or if symptoms worsen at any time. 1, 2, 3 The number needed to treat (NNT) is 10–15 to achieve one additional cure compared with placebo. 1

Referral to Otolaryngology

Refer immediately for:

• No improvement after 7 days of appropriate second-line antibiotic therapy 1, 2, 3
• Worsening symptoms at any point 1, 2, 3
• Suspected complications (severe headache, visual changes, periorbital swelling, altered mental status) 1, 2, 3
• Recurrent sinusitis (≥ 3 episodes per year) requiring evaluation for underlying allergic rhinitis, immunodeficiency, or anatomic abnormalities 1, 2, 3

Common Pitfalls

• Do not prescribe antibiotics for symptoms < 10 days unless severe features are present 1, 2, 3
• Avoid routine imaging (X-ray or CT) for uncomplicated sinusitis; up to 87% of viral URIs show sinus abnormalities on imaging 1
• Ensure adequate treatment duration (≥ 5 days for adults) to prevent relapse 1, 3
• Gastrointestinal adverse effects with amoxicillin-clavulanate are common: diarrhea in 40–43% of patients, severe diarrhea in 7–8% 1, 5