What is the recommended dose of azithromycin (Zithromax) for a sinus infection?

Azithromycin Dosing for Acute Bacterial Sinusitis

Azithromycin should NOT be used as first-line therapy for acute bacterial sinusitis due to significant resistance patterns (20-25% failure rates), but if prescribed despite this limitation, the FDA-approved dose is 500 mg once daily for 3 days. 1

Why Azithromycin is Not Recommended

The American Academy of Pediatrics explicitly states that azithromycin should not be used to treat acute bacterial sinusitis in persons with penicillin hypersensitivity due to resistance patterns. 2, 3

• Surveillance studies demonstrate significant resistance of Streptococcus pneumoniae and Haemophilus influenzae to azithromycin, making it unsuitable for empiric treatment of sinusitis 2
• French guidelines exclude macrolides, including azithromycin, from recommended therapy due to resistance prevalence 2
• Predicted clinical efficacy is only 77-81% compared to 90-92% for first-line agents like amoxicillin-clavulanate or respiratory fluoroquinolones 4, 3
• Macrolides are relatively weak against penicillin-resistant H. influenzae and S. pneumoniae, which are common pathogens in sinusitis 3

FDA-Approved Dosing (If Used Despite Limitations)

For adults with acute bacterial sinusitis, the FDA-approved regimen is 500 mg once daily for 3 days. 1

For pediatric patients (age 6 months and above), the dose is 10 mg/kg once daily for 3 days. 1

Pediatric Dosing Table (3-Day Regimen):

• 5 kg (11 lbs): 2.5 mL of 100 mg/5 mL suspension = 150 mg total course 1
• 10 kg (22 lbs): 5 mL of 100 mg/5 mL suspension = 300 mg total course 1
• 20 kg (44 lbs): 5 mL of 200 mg/5 mL suspension = 600 mg total course 1
• 30 kg (66 lbs): 7.5 mL of 200 mg/5 mL suspension = 900 mg total course 1
• 40 kg (88 lbs): 10 mL of 200 mg/5 mL suspension = 1200 mg total course 1

What You Should Use Instead

Amoxicillin or high-dose amoxicillin-clavulanate are the recommended first-line treatments for acute bacterial sinusitis. 2, 3

First-Line Options:

• Amoxicillin 500 mg twice daily for mild disease without recent antibiotic exposure 2
• Amoxicillin 875 mg twice daily for more severe infections 2
• High-dose amoxicillin-clavulanate (875 mg/125 mg twice daily) for patients with recent antibiotic use or moderate disease 2
• Treatment duration: 5-10 days, typically until symptom-free for 7 days 2, 3

For Penicillin-Allergic Patients:

• Second-generation cephalosporins (cefuroxime-axetil) or third-generation cephalosporins (cefpodoxime-proxetil, cefdinir) for non-Type I allergies 2, 3
• Respiratory fluoroquinolones (levofloxacin 500 mg once daily or moxifloxacin 400 mg once daily) for true Type I penicillin allergy 2, 3

Clinical Evidence for Azithromycin (Historical Context)

While older studies showed azithromycin had comparable efficacy to amoxicillin-clavulanate in the 1990s, these findings are no longer clinically relevant due to evolved resistance patterns:

• A 1991 study showed 100% clinical response rates with azithromycin 500 mg day 1, then 250 mg days 2-5 5
• A 2003 study found 3-day and 6-day azithromycin regimens equivalent to 10-day amoxicillin-clavulanate 6
• However, these studies predate current resistance surveillance data that now contraindicate azithromycin use 2, 3

Critical Pitfalls to Avoid

• Never use azithromycin as routine first-line therapy for acute bacterial sinusitis due to 20-25% bacteriologic failure rates 4, 2
• Do not prescribe azithromycin for penicillin-allergic patients as an alternative—use cephalosporins or fluoroquinolones instead 2, 3
• Reassess at 3-5 days if no improvement occurs, and switch to appropriate second-line therapy (high-dose amoxicillin-clavulanate or respiratory fluoroquinolones) 2, 3
• Ensure antibiotics are truly indicated: most acute rhinosinusitis is viral and resolves without antibiotics within 7-10 days 2