Azithromycin for Sore Throat

Azithromycin is not recommended as first-line therapy for sore throat but is a reasonable alternative for patients with penicillin allergy. 1

First-Line Treatment Recommendations

Penicillin remains the treatment of choice for streptococcal pharyngitis due to its proven efficacy, safety, narrow spectrum, and low cost 1
Amoxicillin is often used in place of penicillin V for young children due to better taste acceptance and is equally effective 1
Group A streptococci have never developed resistance to penicillin anywhere in the world 1, 2

Azithromycin is a reasonable alternative for patients with penicillin allergy 1
A systematic review found no evidence of differing efficacy between azithromycin and comparator agents (including penicillin) for acute pharyngitis 1
Azithromycin is given for 5 days (compared to 10 days for penicillin) due to its prolonged tissue half-life 1, 3
FDA-approved dosing for streptococcal pharyngitis is 12 mg/kg once daily for 5 days in children 4

In clinical trials, azithromycin was statistically superior to penicillin at Day 14 and Day 30 with clinical success rates of 98% vs 84% and 94% vs 74%, respectively 4
However, bacterial eradication rates with azithromycin decline over time (77% at Day 30 compared to 95% at Day 14) 4
Approximately 1% of azithromycin-susceptible S. pyogenes isolates became resistant following therapy 4
A Cochrane review found insufficient evidence to conclude that azithromycin or other antibiotics are more effective than penicillin in treating streptococcal pharyngitis 5

Macrolide resistance rates among pharyngeal Group A streptococcal isolates in the US are approximately 5-8%, which can result in treatment failures 1, 2
This resistance rate is higher than for penicillin (0% resistance) or clindamycin (approximately 1% resistance) 1, 2

Azithromycin has a higher incidence of treatment-related adverse events compared to penicillin (18% vs 13%) 4
The most common side effects are gastrointestinal: diarrhea/loose stools (6% azithromycin vs 2% penicillin), vomiting (6% azithromycin vs 4% penicillin), and abdominal pain (3% azithromycin vs 1% penicillin) 4
Macrolides, including azithromycin (though to a lesser extent), can cause prolongation of the QT interval in a dose-dependent manner 1

First-line therapy: Penicillin V or amoxicillin for 10 days 1
For penicillin-allergic patients (non-anaphylactic): First-generation cephalosporins (cefadroxil or cephalexin) for 10 days 1
For penicillin-allergic patients (anaphylactic-type): Azithromycin for 5 days or clindamycin for 10 days 1

Penicillin remains the drug of choice because it has the narrowest spectrum and lowest cost while maintaining excellent efficacy 1
Azithromycin's convenience (5-day course, once-daily dosing) must be balanced against higher rates of gastrointestinal side effects and potential for resistance development 4, 6
Antibiotics should only be prescribed for confirmed or highly suspected streptococcal pharyngitis, not viral sore throats 1