Azithromycin for Strep Throat
Azithromycin is an acceptable alternative for treating strep throat in penicillin-allergic patients, but it is not recommended as first-line therapy due to increasing resistance rates and should be reserved for patients who cannot take penicillin. 1
First-Line Treatment Options
- Penicillin and amoxicillin remain the drugs of choice for Group A Streptococcal (GAS) pharyngitis due to their proven efficacy, safety, narrow spectrum, and low cost 1
- Penicillin-resistant GAS has never been documented anywhere in the world, making penicillin the most reliable first-line option 2
- The standard treatment regimen for penicillin is 10 days to achieve maximal pharyngeal eradication of GAS 1
Role of Azithromycin in Strep Throat
- Azithromycin is recommended only for patients with penicillin allergy, with a 5-day course due to its prolonged tissue half-life 1
- FDA-approved azithromycin dosing for streptococcal pharyngitis is 12 mg/kg once daily for 5 days in children 3
- In clinical trials, azithromycin demonstrated superior bacteriologic eradication rates compared to penicillin at Day 14 (95% vs 73%) and Day 30 (77% vs 63%) 3
- Despite good clinical efficacy, macrolide resistance rates among GAS pharyngeal isolates in the US have increased to approximately 5-8%, which can result in treatment failures 1, 2
Treatment Algorithm for Strep Throat
First-line therapy (non-allergic patients):
For penicillin-allergic patients (in order of preference):
- Narrow-spectrum cephalosporins (if no immediate hypersensitivity to penicillin): cefadroxil or cephalexin for 10 days 1
- Clindamycin: 7 mg/kg three times daily (maximum 300 mg per dose) for 10 days - has very low resistance rate (approximately 1%) 1
- Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days 1, 3
Efficacy and Safety Considerations
- While azithromycin offers the convenience of shorter treatment duration (5 days vs 10 days), this must be balanced against increasing resistance concerns 4, 5
- Gastrointestinal side effects are common with azithromycin (18% overall), including diarrhea/loose stools (6%), vomiting (6%), and abdominal pain (3%) 3
- Macrolides, including azithromycin, can cause QT interval prolongation in a dose-dependent manner, though this is less common with azithromycin than with erythromycin 1
- Drug interactions are possible as macrolides are metabolized by cytochrome P-450 3A and should not be taken with inhibitors of this enzyme 1
Important Clinical Considerations
- Treatment of GAS pharyngitis is primarily aimed at preventing rheumatic fever, but data establishing azithromycin's efficacy in preventing rheumatic fever are not available 3
- Some studies have shown that a total dose of 60 mg/kg azithromycin (given as either 12 mg/kg daily for 5 days or 20 mg/kg daily for 3 days) provides the best rate of GAS eradication 4
- Routine post-treatment testing is not recommended unless the patient remains symptomatic, symptoms recur, or the patient has a history of rheumatic fever 1, 2
- Tetracyclines, sulfonamides, trimethoprim-sulfamethoxazole, and older fluoroquinolones should not be used to treat GAS pharyngitis due to resistance or ineffectiveness 1
Pitfalls and Caveats
- Despite good clinical response rates, bacteriological eradication with azithromycin may be inferior to penicillin in some studies, particularly with the 3-day regimen 6
- Increasing macrolide resistance means azithromycin should not replace penicillin as first-line therapy 1, 2
- Approximately 1% of azithromycin-susceptible S. pyogenes isolates may become resistant following therapy 3
- The shorter course of azithromycin may improve compliance compared to 10-day penicillin regimens, but this benefit must be weighed against the risk of increasing antibiotic resistance 4, 5