What is the first‑line antibiotic for uncomplicated group A Streptococcal pharyngitis?

Best Antibiotic for Throat Infection

Penicillin or amoxicillin is the best antibiotic for uncomplicated Group A streptococcal pharyngitis because of proven efficacy, safety, narrow spectrum, low cost, and zero documented resistance worldwide. 1, 2

First-Line Treatment for Non-Allergic Patients

Prescribe oral penicillin V or amoxicillin for a full 10-day course. 1, 2, 3

Dosing Regimens

Adults:

• Penicillin V: 500 mg twice daily for 10 days 3, 4
• Amoxicillin: 500 mg twice daily for 10 days 3, 4

Children:

• Amoxicillin: 50 mg/kg once daily (maximum 1000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days 2, 4
• Penicillin V: 250 mg twice or three times daily for 10 days 4

Amoxicillin is preferred over penicillin V in young children because of better palatability and availability as a liquid suspension, though both have identical efficacy. 1, 2

Why the Full 10-Day Course Is Mandatory

Even if symptoms resolve within 3–4 days, the entire 10-day regimen must be completed to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever. 1, 2, 3 Shortening the course by even a few days leads to appreciable increases in treatment-failure rates and rheumatic-fever risk. 2, 4

Treatment for Penicillin-Allergic Patients

Step 1: Determine the Type of Allergic Reaction

Immediate/anaphylactic reactions (anaphylaxis, angioedema, respiratory distress, or urticaria within 1 hour) carry up to 10% cross-reactivity with all beta-lactam antibiotics, including cephalosporins. 2

Non-immediate (delayed) reactions (mild rash or skin symptoms occurring >1 hour after exposure) have only 0.1% cross-reactivity with first-generation cephalosporins. 2

For Non-Immediate Penicillin Allergy

First-generation cephalosporins are the preferred first-line alternatives with strong, high-quality evidence. 2, 4

Adults:

• Cephalexin: 500 mg twice daily for 10 days 2, 3
• Cefadroxil: 1 g once daily for 10 days 2, 3

Children:

• Cephalexin: 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days 2, 4
• Cefadroxil: 30 mg/kg once daily (maximum 1 g) for 10 days 2, 4

For Immediate/Anaphylactic Penicillin Allergy

Clindamycin is the preferred choice because all beta-lactams must be avoided, and clindamycin has only ~1% resistance among U.S. Group A Streptococcus isolates with superior eradication rates even in chronic carriers. 2, 4

Adults:

• Clindamycin: 300 mg three times daily for 10 days 2, 3

Children:

• Clindamycin: 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days 2, 4

Macrolide Alternatives (Less Preferred)

Macrolides should be used only when clindamycin cannot be used because macrolide resistance ranges from 5–8% in the United States and varies geographically. 2, 4

Azithromycin:

• Adults: 500 mg once daily for 5 days 2, 3
• Children: 12 mg/kg once daily (maximum 500 mg) for 5 days 2, 4
• Azithromycin is the only antibiotic requiring just 5 days due to its prolonged tissue half-life. 2, 4

Clarithromycin:

• Adults: 250 mg twice daily for 10 days 2, 3
• Children: 7.5 mg/kg per dose twice daily (maximum 250 mg per dose) for 10 days 2, 4

When to Use Intramuscular Penicillin

Intramuscular benzathine penicillin G should be used when oral compliance is uncertain or in populations where follow-up is lacking and rheumatic fever remains prevalent. 1, 3, 4

Dosing:

• <27 kg: 600,000 units as a single dose 4
• ≥27 kg: 1.2 million units as a single dose 3, 4

Critical Pitfalls to Avoid

Do not prescribe cephalosporins to patients with immediate/anaphylactic penicillin reactions due to the ~10% cross-reactivity risk. 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. 2, 4

Do not use trimethoprim-sulfamethoxazole (Bactrim) because sulfonamides fail to eradicate Group A Streptococcus in 20–25% of cases. 2, 4

Do not prescribe tetracyclines due to high prevalence of resistant strains. 2

Do not prescribe antibiotics without confirming Group A Streptococcus infection with a rapid antigen detection test or throat culture, because most pharyngitis cases are viral. 2, 3

Adjunctive Symptomatic Treatment

Offer acetaminophen or ibuprofen for moderate-to-severe sore throat, fever, or systemic discomfort. 2, 4

Avoid aspirin in children due to the risk of Reye syndrome. 2, 4

Corticosteroids are not recommended as adjunctive therapy for streptococcal pharyngitis. 2, 4

Management of Treatment Failure

If initial therapy with penicillin or amoxicillin fails, prescribe clindamycin because it achieves substantially higher eradication rates than penicillin in chronic carriers and persistent infections. 2

Clindamycin for treatment failure:

• Adults: 300 mg three times daily for 10 days 2
• Children: 20–30 mg/kg/day divided into 3 doses (maximum 300 mg per dose) for 10 days 2

Alternative regimens for chronic carriers:

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

Chronic carriers generally do not require treatment unless special circumstances exist, such as community outbreak of rheumatic fever, family history of rheumatic fever, or excessive family anxiety. 2