Is Azithromycin (a macrolide antibiotic) effective for treating chronic rhinosinusitis?

Azithromycin for Chronic Rhinosinusitis: Limited Efficacy and Not First-Line

Azithromycin is not recommended as first-line therapy for chronic rhinosinusitis due to limited efficacy, increasing antimicrobial resistance, and availability of more effective treatment options. 1

Evidence Assessment

Guideline Recommendations

The European Position Paper on Rhinosinusitis and Nasal Polyps (2020) does not support routine use of azithromycin for chronic rhinosinusitis, noting inconsistent results across studies 1. Similarly, the American Academy of Otolaryngology guidelines place azithromycin in a lower efficacy tier (77-81% predicted clinical efficacy) compared to other antibiotics for rhinosinusitis 1.

Efficacy Concerns

• Azithromycin shows significantly lower predicted clinical efficacy (77-81%) compared to respiratory quinolones, ceftriaxone, and amoxicillin/clavulanate (90-92%) for rhinosinusitis 1
• Increasing resistance rates to macrolides, including azithromycin, have been documented globally, particularly for S. pneumoniae 2
• The long half-life of azithromycin creates prolonged periods of subinhibitory concentrations, potentially promoting resistance development 2

Treatment Algorithm for Chronic Rhinosinusitis

First-Line Treatments

1. Intranasal corticosteroids - Primary therapy with strongest evidence base
2. Saline nasal irrigation - Adjunctive therapy to improve mucociliary clearance
3. For acute bacterial exacerbations requiring antibiotics:
   • First choice: Amoxicillin-clavulanate (higher efficacy tier of 90-92%) 1
   • Alternative: Respiratory fluoroquinolones (for adults with moderate-severe disease or penicillin allergy) 1

When to Consider Azithromycin

Azithromycin should be reserved for specific situations:

1. Penicillin-allergic patients who cannot tolerate respiratory fluoroquinolones
2. Refractory cases failing first-line antibiotics and intranasal corticosteroids
3. Post-endoscopic sinus surgery patients with persistent symptoms despite corticosteroid irrigations 3

Dosing for Chronic Rhinosinusitis (when used)

• Low-dose, long-term regimen: 250 mg three times weekly for 8-12 weeks 4, 3
• Not recommended as monotherapy for initial treatment

Special Considerations

Potential Benefits in Specific Subgroups

One randomized controlled trial found that low-dose azithromycin (250 mg three times weekly for 16 weeks) showed improved disease clearance in non-aspirin-exacerbated respiratory disease patients who had failed endoscopic sinus surgery and budesonide nasal irrigations 4. However, this represents a very specific subgroup of patients with refractory disease.

Limitations and Risks

• Gastrointestinal side effects are common (reported in 23-27% of patients) 5, 6
• Increasing antimicrobial resistance concerns with macrolide use 2
• Multiple studies show lack of efficacy in general chronic rhinosinusitis populations 5

Key Takeaways

1. Azithromycin should not be used as first-line therapy for chronic rhinosinusitis
2. Intranasal corticosteroids remain the cornerstone of treatment
3. When antibiotics are necessary, amoxicillin-clavulanate or respiratory fluoroquinolones are preferred over azithromycin
4. Azithromycin may have a limited role in specific refractory cases, particularly after endoscopic sinus surgery
5. Antimicrobial stewardship principles should guide antibiotic selection to minimize resistance development