What is the first-line antibiotic for acute streptococcal pharyngitis (group A Streptococcus)?

First-Line Antibiotic for Strep Throat

Penicillin V (250 mg three to four times daily or 500 mg twice daily for 10 days) or amoxicillin (50 mg/kg once daily, maximum 1000 mg, for 10 days) are the first-line antibiotics for acute streptococcal pharyngitis in patients without penicillin allergy. 1

Why Penicillin or Amoxicillin Remain First-Line

• No documented penicillin resistance exists anywhere in the world among Group A Streptococcus, ensuring reliable bactericidal activity and pharyngeal eradication. 2
• Penicillin V and amoxicillin offer proven efficacy, narrow antimicrobial spectrum, excellent safety profile, and low cost compared to all alternatives. 1
• Amoxicillin is preferred over penicillin V in younger children because of superior palatability and availability as a liquid suspension, improving adherence despite identical efficacy. 1

Critical Treatment Duration

• A full 10-day course is mandatory to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever, even if symptoms resolve within 3–4 days. 2, 1
• Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk. 2
• Meta-analyses confirm that short-course penicillin (≤5 days) is significantly less effective for both clinical cure (OR 0.43) and bacteriological eradication (OR 0.34) compared to the standard 10-day regimen. 3

Alternatives for Penicillin-Allergic Patients

Non-Immediate (Delayed) Penicillin Allergy

• First-generation cephalosporins (cephalexin 500 mg twice daily or cefadroxil 1 gram once daily for 10 days) are the preferred alternatives, with strong, high-quality evidence and only 0.1% cross-reactivity risk in patients with delayed, non-severe reactions. 2, 1

Immediate/Anaphylactic Penicillin Allergy

• Clindamycin (300 mg three times daily for 10 days) is the preferred choice when all beta-lactams must be avoided, with approximately 1% resistance among U.S. Group A Streptococcus isolates and superior eradication rates even in chronic carriers. 2, 1
• All beta-lactam antibiotics, including cephalosporins, must be avoided in patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, urticaria within 1 hour) due to up to 10% cross-reactivity risk. 2

Macrolide Alternatives (Less Preferred)

• Azithromycin (500 mg once daily for 5 days) or clarithromycin (250 mg twice daily for 10 days) are acceptable alternatives when clindamycin cannot be used, but macrolide resistance ranges from 5–8% in the United States and varies geographically. 2, 1
• Azithromycin is the only antibiotic that requires just 5 days due to its prolonged tissue half-life; all other agents require the full 10-day course. 2

Common Pitfalls to Avoid

• Do not prescribe cephalosporins to patients with immediate/anaphylactic penicillin reactions due to the ~10% cross-reactivity risk. 2
• Do not use trimethoprim-sulfamethoxazole (Bactrim), as resistance rates approach 50% and sulfonamides fail to eradicate Group A Streptococcus in 20–25% of cases. 2, 1
• Do not use tetracyclines or sulfonamides due to high resistance rates among Group A Streptococcus. 4, 1
• 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, 1

Adjunctive Symptomatic Management

• Offer acetaminophen or NSAIDs (ibuprofen) for moderate to severe sore throat, fever, or systemic discomfort. 2
• Avoid aspirin in children due to the risk of Reye syndrome. 2
• Corticosteroids are not recommended as adjunctive therapy for streptococcal pharyngitis. 2