Is azithromycin (Zithromax) effective for treating streptococcal pharyngitis (strep throat)?

Azithromycin for Strep Throat Treatment

Azithromycin is an acceptable second-line treatment for strep throat, but should only be used in patients with penicillin allergy as penicillin/amoxicillin remains the first-line treatment of choice. 1

First-Line Treatment Options

• Penicillin or amoxicillin is the recommended first-choice antibiotic for Group A Streptococcal (GAS) pharyngitis due to:
  • Narrow spectrum of activity
  • Proven efficacy
  • Infrequent adverse reactions
  • Low cost
  • Decades of documented prevention of rheumatic fever 1

When to Consider Azithromycin

Azithromycin should be reserved for patients with:

• Documented penicillin allergy
• Inability to tolerate first-line agents

The recommended dosage for azithromycin in strep throat is:

• 12 mg/kg once daily (maximum = 500 mg) for 5 days 1, 2, 3

Efficacy of Azithromycin vs. First-Line Agents

The FDA label shows that azithromycin has demonstrated clinical efficacy in the treatment of strep throat:

• In controlled studies, azithromycin was clinically and microbiologically superior to penicillin at Day 14 and Day 30 3
• Clinical success rates (cure plus improvement) were 98% for azithromycin vs. 84% for penicillin at Day 14 3
• Bacteriologic eradication rates were 95% for azithromycin vs. 73% for penicillin at Day 14 3

However, several important limitations exist:

1. Resistance concerns: Macrolide resistance rates among GAS isolates in the US are around 5-8%, while resistance to penicillin remains virtually nonexistent 1

2. Variable eradication rates: Some studies have shown inferior bacteriologic eradication with azithromycin compared to penicillin (65% vs. 82%) 4

3. Duration concerns: 10 days of clarithromycin therapy has been shown to be more effective than 5 days of azithromycin in eradicating GAS (91% vs. 82%) 5

Treatment Algorithm

1. First-line treatment (for non-allergic patients):

   • Penicillin V or amoxicillin for 10 days

2. Second-line options (for penicillin-allergic patients):

   • For non-anaphylactic penicillin allergy:
     • First-generation cephalosporin (e.g., cephalexin) for 10 days
   • For anaphylactic penicillin allergy:
     • Azithromycin 12 mg/kg once daily (max 500 mg) for 5 days, OR
     • Clarithromycin 7.5 mg/kg twice daily (max 250 mg per dose) for 10 days, OR
     • Clindamycin for 10 days (if macrolide resistance is a concern) 1, 2

Safety Considerations

• Gastrointestinal side effects are more common with azithromycin than with penicillin:

  • Diarrhea/loose stools (6% azithromycin vs. 2% penicillin)
  • Vomiting (6% azithromycin vs. 4% penicillin)
  • Abdominal pain (3% azithromycin vs. 1% penicillin) 3

• Macrolide resistance should be considered in areas with high prevalence of resistant strains 1

Important Caveats

1. Confirm diagnosis before treatment: Use rapid antigen detection test (RADT) and/or throat culture to confirm GAS pharyngitis before initiating antibiotics 2

2. Complete the full course: Emphasize the importance of completing the full 5-day course of azithromycin to maximize eradication and prevent complications 1

3. Monitor for treatment failure: Be alert for persistent symptoms beyond 48-72 hours of treatment, which may indicate treatment failure or macrolide resistance 2

4. Consider local resistance patterns: In areas with high macrolide resistance, clindamycin may be a better alternative for penicillin-allergic patients 1, 2

5. Prevention of rheumatic fever: While azithromycin is effective for treating strep throat, data establishing its efficacy in preventing rheumatic fever (unlike penicillin) are limited 3