What is the first‑line treatment for acute Group A streptococcal pharyngitis and the recommended alternatives for patients with penicillin allergy?

First-Line Treatment for Strep Throat

For patients without penicillin allergy, prescribe penicillin or amoxicillin for 10 days; for penicillin-allergic patients with non-immediate reactions, use a first-generation cephalosporin (cephalexin or cefadroxil) for 10 days; for immediate/anaphylactic penicillin allergy, clindamycin is the preferred choice for 10 days. 1

Standard First-Line Therapy (Non-Allergic Patients)

Penicillin or amoxicillin remains the drug of choice based on narrow spectrum, proven efficacy, safety profile, modest cost, and zero documented resistance worldwide. 1, 2

Dosing Regimens:

• Amoxicillin: 50 mg/kg once daily (max 1000 mg) or 25 mg/kg twice daily (max 500 mg/dose) for 10 days in children 1, 2
• Amoxicillin (adults): 500 mg twice daily for 10 days 2
• Penicillin V: 250 mg three times daily for 10 days 1

Amoxicillin is preferred over penicillin V in younger children due to better palatability and availability as suspension, though both have identical efficacy. 2

Treatment for Penicillin-Allergic Patients

Step 1: Determine the Type of Allergic Reaction

This is the critical first decision point that determines which antibiotics are safe. 2

• Immediate/anaphylactic reactions (anaphylaxis, angioedema, respiratory distress, urticaria within 1 hour): Up to 10% cross-reactivity with all β-lactams including cephalosporins—avoid all cephalosporins 1, 2
• Non-immediate reactions (mild rash, delayed symptoms >1 hour): Only 0.1% cross-reactivity with first-generation cephalosporins—cephalosporins are safe 2

For Non-Immediate Penicillin Allergy:

First-generation cephalosporins are the preferred first-line alternatives with strong, high-quality evidence. 1, 2

• Cephalexin: 20 mg/kg/dose twice daily (max 500 mg/dose) for 10 days in children; 500 mg twice daily for 10 days in adults 1, 2
• Cefadroxil: 30 mg/kg once daily (max 1 g) for 10 days in children; 1 g once daily for 10 days in adults 1, 2

Why cephalosporins are preferred: Narrow spectrum, proven efficacy, essentially zero resistance, lower cost than macrolides, and stronger evidence (strong, high-quality) compared to macrolides (strong, moderate-quality). 2

For Immediate/Anaphylactic Penicillin Allergy:

Clindamycin is the preferred choice due to only ~1% resistance among U.S. Group A Streptococcus isolates and superior eradication rates even in chronic carriers. 1, 2

• Clindamycin: 7 mg/kg/dose three times daily (max 300 mg/dose) for 10 days in children; 300 mg three times daily for 10 days in adults 1, 2

Alternative macrolide options (when clindamycin cannot be used):

• Azithromycin: 12 mg/kg once daily (max 500 mg) for 5 days in children; 500 mg once daily for 5 days in adults 1, 2
• Clarithromycin: 7.5 mg/kg/dose twice daily (max 250 mg/dose) for 10 days in children; 250 mg twice daily for 10 days in adults 1, 2

Macrolides are less reliable than clindamycin because resistance rates in the U.S. are 5-8% and vary geographically, whereas clindamycin resistance is only ~1%. 1, 2

Critical Treatment Duration Requirements

A full 10-day course is mandatory for all antibiotics except azithromycin to achieve maximal pharyngeal eradication and prevent acute rheumatic fever. 1, 2

• Shortening the course by even a few days dramatically increases treatment failure rates and rheumatic fever risk 1, 2
• Azithromycin is the only exception requiring just 5 days due to its prolonged tissue half-life 1, 2, 3
• Even if symptoms resolve in 3-4 days, the full 10-day course must be completed 2

Adjunctive Symptomatic Treatment

• Acetaminophen or NSAIDs (ibuprofen) for moderate to severe symptoms or high fever 1, 2
• Avoid aspirin in children due to Reye syndrome risk 1, 2
• Corticosteroids are not recommended as adjunctive therapy 1, 2

Common Pitfalls to Avoid

1. Do not prescribe cephalosporins to patients with immediate/anaphylactic penicillin reactions due to the ~10% cross-reactivity risk 1, 2

2. Do not shorten antibiotic courses below 10 days (except azithromycin's 5-day regimen)—this markedly increases treatment failure and rheumatic fever risk 1, 2

3. Do not use trimethoprim-sulfamethoxazole (Bactrim) for strep throat—it fails to eradicate Group A Streptococcus in 20-25% of cases 2

4. Do not prescribe broad-spectrum cephalosporins (cefdinir, cefuroxime, cefpodoxime) when narrow-spectrum first-generation agents are appropriate—they are more expensive and promote resistant flora 2

5. Do not order routine post-treatment throat cultures for asymptomatic patients who completed therapy—reserve for special circumstances like history of rheumatic fever 1, 2

6. Do not use macrolides as first-line therapy when penicillin or cephalosporins can be used—reserve for true immediate penicillin allergy 2

Management of Treatment Failure

If initial therapy with amoxicillin or cephalexin fails, clindamycin is the optimal choice because it demonstrates substantially higher eradication rates in treatment failures and chronic carriers. 2

• Clindamycin: 300 mg three times daily for 10 days (adults); 7 mg/kg/dose three times daily for 10 days (children, max 300 mg/dose) 2

Consider whether the patient is a chronic carrier experiencing repeated viral infections rather than true recurrent streptococcal infections—chronic carriers generally do not require treatment. 1, 2