What is the recommended treatment for confirmed Group A streptococcal pharyngitis, including first‑line antibiotics and alternatives for penicillin allergy?

Treatment of Streptococcal Pharyngitis

For confirmed Group A streptococcal pharyngitis, prescribe oral penicillin V or amoxicillin for a full 10 days as first-line therapy; for patients with non-anaphylactic penicillin allergy, use a first-generation cephalosporin (cephalexin or cefadroxil) for 10 days; for immediate/anaphylactic penicillin reactions, prescribe clindamycin for 10 days. 1, 2

First-Line Antibiotic Therapy

Penicillin and amoxicillin remain the drugs of choice due to proven efficacy, narrow antimicrobial spectrum, excellent safety profile, low cost, and the complete absence of documented penicillin resistance in Group A Streptococcus anywhere in the world. 1, 2

Recommended Dosing Regimens

Adults:

• Penicillin V: 250 mg orally four times daily OR 500 mg twice daily for 10 days 1
• Amoxicillin: 500 mg twice daily OR 1000 mg once daily for 10 days 1, 2

Children:

• Penicillin V: 250 mg orally two or three times daily for 10 days 1
• Amoxicillin: 50 mg/kg once daily (maximum 1000 mg) OR 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days 1, 2

Amoxicillin is preferred over penicillin V in younger children because of superior palatability and availability as a liquid suspension, though both have identical efficacy. 2

Treatment for Penicillin-Allergic Patients

Non-Immediate (Delayed) Penicillin Allergy

First-generation cephalosporins are the preferred alternatives with strong, high-quality evidence supporting their efficacy. 1, 2 The cross-reactivity risk is only 0.1% in patients with non-severe, delayed penicillin reactions (mild rash occurring >1 hour after exposure). 2

Recommended regimens:

• Cephalexin: Adults 500 mg twice daily for 10 days; Children 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days 1, 2
• Cefadroxil: Adults 1 gram once daily for 10 days; Children 30 mg/kg once daily (maximum 1 gram) for 10 days 1, 2

Immediate/Anaphylactic Penicillin Allergy

All beta-lactam antibiotics must be avoided in patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, respiratory distress, or urticaria occurring within 1 hour of penicillin exposure) due to up to 10% cross-reactivity risk with cephalosporins. 1, 2

Clindamycin is the preferred choice with strong, moderate-quality evidence, approximately 1% resistance among Group A Streptococcus in the United States, and demonstrated high efficacy even in chronic carriers and treatment failures. 1, 2

Clindamycin dosing:

• Adults: 300 mg orally three times daily for 10 days 1, 2
• Children: 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days 1, 2

Alternative macrolide options (less preferred due to resistance):

• Azithromycin: Adults 500 mg once daily for 5 days; Children 12 mg/kg once daily (maximum 500 mg) for 5 days 1, 2, 3, 4
• Clarithromycin: Adults 250 mg twice daily for 10 days; Children 7.5 mg/kg per dose twice daily (maximum 250 mg per dose) for 10 days 1, 2

Macrolide resistance among Group A Streptococcus ranges from 5-8% in the United States and varies geographically, making clindamycin more reliable when beta-lactams cannot be used. 1, 2, 3

Critical Treatment Duration Requirements

A full 10-day course is mandatory for all antibiotics except azithromycin to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever. 1, 2 Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk. 1, 2

Azithromycin is the only exception, requiring only 5 days due to its prolonged tissue half-life and unique pharmacokinetics. 1, 2, 3, 4

Diagnostic Confirmation Before Treatment

Confirm Group A Streptococcus infection with a rapid antigen detection test (RADT) or throat culture before prescribing antibiotics, as clinical features alone cannot reliably differentiate bacterial from viral pharyngitis. 1, 2, 5

• A positive RADT is diagnostic and does not require backup culture 1, 2
• A negative RADT in children and adolescents should be followed by throat culture 1, 2
• Backup culture is generally not necessary in adults due to low incidence and rheumatic fever risk, though it can be considered 1

Adjunctive Symptomatic Treatment

Offer acetaminophen or NSAIDs (ibuprofen) for moderate to severe symptoms or high fever with strong, high-quality evidence for reducing pain and inflammation. 1, 2, 3

Aspirin must be avoided in children due to the risk of Reye syndrome. 1, 2, 3

Corticosteroids are not recommended as adjunctive therapy for streptococcal pharyngitis. 1, 2, 3

Management of Treatment Failure

If initial therapy with penicillin, amoxicillin, or cephalexin fails, prescribe clindamycin at the doses listed above for 10 days. 2 Clindamycin demonstrates substantially higher eradication rates than penicillin or amoxicillin in eliminating chronic streptococcal carriage and treating persistent infections. 1, 2

Alternative regimens for treatment failures or chronic carriers:

• Amoxicillin-clavulanate: 40 mg/kg/day amoxicillin component in 3 doses (maximum 2000 mg/day) for 10 days 2
• Penicillin V plus rifampin: Penicillin V 50 mg/kg/day in 4 doses for 10 days (maximum 2000 mg/day) with rifampin 20 mg/kg/day in 1 dose for the last 4 days (maximum 600 mg/day) 2

Common Pitfalls to Avoid

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

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

Do not prescribe trimethoprim-sulfamethoxazole (Bactrim) for streptococcal pharyngitis, as sulfonamides fail to eradicate Group A Streptococcus in 20-25% of cases. 2

Do not order routine post-treatment throat cultures for asymptomatic patients who have completed therapy; reserve testing for special circumstances such as history of rheumatic fever. 1, 2

Do not prescribe broad-spectrum cephalosporins (cefuroxime, cefdinir, cefpodoxime) when narrow-spectrum first-generation agents are appropriate, as they are more expensive and more likely to select for antibiotic-resistant flora. 2

Special Considerations

Chronic carriers generally do not require treatment unless special circumstances exist (community outbreak of rheumatic fever or invasive Group A Streptococcus, family history of rheumatic fever, excessive family anxiety, or tonsillectomy being considered). 1, 2 They are unlikely to spread infection and are at very low risk for complications. 1, 2

Therapy can be safely postponed up to 9 days after symptom onset and still prevent acute rheumatic fever. 2