What is the recommended long-term macrolide (macrolide antibiotic) regimen for chronic rhinosinusitis (CRS) without nasal polyps?

Long-Term Macrolide Regimen for Chronic Rhinosinusitis Without Nasal Polyps

For CRS without nasal polyps, roxithromycin 150 mg daily for 12 weeks is the recommended regimen, particularly in patients with low IgE levels (<200 μg/L), as this is the only regimen that demonstrated significant improvements in quality of life, endoscopy scores, and mucociliary clearance in this specific population. 1

Patient Selection Criteria

Before initiating long-term macrolide therapy, confirm the following:

• Diagnosis confirmation: Symptoms lasting >12 weeks with purulent drainage visible on nasal examination 2
• Failed optimization: Patient must have already optimized intranasal corticosteroids and saline irrigations without adequate response 2
• IgE level assessment: Check serum IgE levels, as patients with low IgE (<200 μg/L) show 93% improvement rates versus minimal response in high IgE patients 1
• Polyp status: Confirm absence of nasal polyps, as the evidence for roxithromycin is specific to CRS without polyps 1

Recommended Regimen

Roxithromycin 150 mg once daily for 12 weeks is the evidence-based choice for CRSsNP 1. This regimen demonstrated:

• Significant improvement in SNOT-20 scores (mean difference -0.54 points) 1
• Improved nasal endoscopy findings 1
• Enhanced saccharin transit time (mucociliary clearance) 1
• 67% response rate versus 22% in placebo 1

Alternative Regimens (Lower Quality Evidence)

If roxithromycin is unavailable, consider these alternatives with important caveats:

• Azithromycin 500 mg weekly for 12 weeks: Showed no significant benefit during treatment in mixed CRS populations, though 50% reported improvement 12 weeks post-treatment versus 9% with placebo 1, 3. This regimen has contradictory evidence and should be considered second-line 2

• Azithromycin 250 mg daily for 12 weeks: Limited evidence in CRSsNP specifically, though this dosing has support in bronchiectasis literature 1, 4

• Erythromycin 250 mg twice daily for 8-12 weeks: Showed trend toward improvement in CRSsNP subgroup but only endoscopy scores reached significance 1

Mandatory Pre-Treatment Safety Screening

Before prescribing any macrolide, obtain:

• ECG to assess QTc interval: Contraindicated if QTc >450 ms (men) or >470 ms (women) 1, 4
• Baseline liver function tests 1, 4
• Sputum culture (if patient can expectorate) to screen for nontuberculous mycobacteria, as macrolide monotherapy must be avoided if NTM present 1
• Medication review: Check for drug interactions, particularly with CYP3A4 substrates (statins, colchicine) 1

Monitoring During Treatment

• Liver function tests at 1 month, then every 6 months 1, 4
• Repeat ECG at 1 month to check for new QTc prolongation 1
• Clinical symptom assessment using validated scores (SNOT-20 or SNOT-22) 1
• Nasal endoscopy to objectively assess mucosal changes 1

Expected Timeline for Response

• Assess efficacy at 12 weeks (end of treatment course) 1, 2
• Consider extended follow-up: Some patients show delayed response 12 weeks after completing treatment 1
• Minimum treatment duration: Full 12-week course required to demonstrate benefit; shorter courses lack evidence 1

Important Caveats and Contraindications

Do not use macrolides if:

• Patient has high IgE levels (>200 μg/L), as response rates drop dramatically 1
• QTc prolongation is present on baseline ECG 1, 4
• Patient has nasal polyps (different treatment paradigm; consider doxycycline instead) 2
• Purulent drainage is absent on examination 2
• Anti-inflammatory treatment has not been optimized first 2

Counsel patients about adverse effects:

• Gastrointestinal disturbances (diarrhea, abdominal cramps) are most common 1
• Cardiac risks including arrhythmias 1
• Hearing and balance disturbances 1
• Development of antimicrobial resistance 1, 4

Evidence Quality Assessment

The evidence for long-term macrolides in CRSsNP is limited but highest quality for roxithromycin. The EPOS 2020 guideline states uncertainty about macrolide efficacy overall due to low quality evidence 1, but the Wallwork 2006 study provides the strongest placebo-controlled evidence specifically for roxithromycin in CRSsNP patients with low IgE 1. The 2025 AAO-HNS guideline notes mixed results across macrolide studies and emphasizes weighing benefits against cardiovascular and other risks 1.

The key differentiator is patient selection: macrolides work in a specific phenotype (CRSsNP with low IgE), not as a broad treatment for all CRS 1.