What is the first‑line oral β‑lactam antibiotic regimen for acute group A streptococcal pharyngitis in adults and children, and what are the recommended alternatives for patients with penicillin allergy?

Antibiotic Treatment for Group A Streptococcal Pharyngitis

First-Line Therapy for Non-Allergic Patients

Penicillin V 500 mg orally twice daily for 10 days or amoxicillin 50 mg/kg once daily (maximum 1000 mg) for 10 days is the first-line treatment for adults and children with confirmed Group A streptococcal pharyngitis. 1

• Amoxicillin is often preferred over penicillin V due to better palatability, particularly in children, and the convenience of once-daily dosing, though both have identical efficacy. 1, 2
• No documented penicillin resistance exists anywhere in the world among Group A Streptococcus, ensuring reliable bacterial eradication. 3
• For children, amoxicillin dosed at 40–50 mg/kg/day yields superior clinical cure (88% vs 71% with lower-dose penicillin V) and higher bacteriologic eradication (79% vs 55%). 3
• Intramuscular benzathine penicillin G (600,000 units if <27 kg; 1,200,000 units if ≥27 kg) as a single dose ensures compliance when adherence to oral therapy is uncertain. 1

Treatment for Penicillin-Allergic Patients

Non-Immediate (Delayed) Penicillin Allergy

For patients with delayed, mild penicillin reactions (e.g., rash occurring >1 hour after exposure), first-generation cephalosporins are the preferred alternatives with strong, high-quality evidence. 3, 1

• Cephalexin 500 mg orally twice daily for 10 days (adults) or 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days (children) is recommended. 3, 1
• Cefadroxil 1 gram once daily for 10 days (adults) or 30 mg/kg once daily (maximum 1 gram) for 10 days (children) is an alternative. 3
• The cross-reactivity risk with first-generation cephalosporins is only 0.1% in patients with non-severe, delayed penicillin reactions. 3

Immediate/Anaphylactic Penicillin Allergy

For patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, urticaria within 1 hour), clindamycin is the preferred choice because all beta-lactam antibiotics carry up to 10% cross-reactivity risk. 3, 1

• Clindamycin 300 mg orally three times daily for 10 days (adults) or 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days (children) is recommended. 3, 1
• Clindamycin demonstrates substantially higher eradication rates than penicillin in chronic carriers and treatment failures, with only approximately 1% resistance among U.S. Group A Streptococcus isolates. 3

Azithromycin 500 mg once daily for 5 days (adults) or 12 mg/kg once daily (maximum 500 mg) for 5 days (children) is an acceptable alternative, but macrolide resistance in the United States ranges from 5% to 8%. 3, 1

• Clarithromycin 250 mg twice daily for 10 days (adults) or 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days (children) is another macrolide option with similar resistance concerns. 3
• Azithromycin is the only antibiotic requiring just 5 days due to its prolonged tissue half-life; all other agents require the full 10-day course. 3, 1

Critical Treatment Duration Requirements

A complete 10-day antibiotic course is mandatory for all agents except azithromycin to achieve maximal pharyngeal eradication and prevent acute rheumatic fever. 3, 1

• Shortening the course by even a few days leads to appreciable increases in treatment failure rates and rheumatic fever risk, even if symptoms resolve within 3–4 days. 3, 1
• The primary goal of treatment is preventing acute rheumatic fever and suppurative complications (peritonsillar abscess, cervical lymphadenitis), not just symptomatic relief. 3

Common Pitfalls to Avoid

Do not prescribe cephalosporins to patients who had anaphylaxis, angioedema, or immediate urticaria to penicillin due to the 10% cross-reactivity risk. 3, 1

• Do not assume all penicillin-allergic patients need to avoid cephalosporins—only those with immediate/anaphylactic reactions should avoid them. 3
• Do not prescribe broad-spectrum cephalosporins (cefaclor, cefuroxime, cefixime, cefdinir, cefpodoxime) when narrow-spectrum first-generation agents are appropriate, as they are more expensive and more likely to select for antibiotic-resistant flora. 3
• Do not use trimethoprim-sulfamethoxazole (Bactrim) for strep throat—it fails to eradicate Group A Streptococcus in 20–25% of cases. 3
• 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. 3

Adjunctive Symptomatic Treatment

Acetaminophen or NSAIDs (such as ibuprofen) should be offered for moderate to severe symptoms or high fever. 3, 1

• Aspirin must be avoided in children due to the risk of Reye syndrome. 3, 1
• Corticosteroids are not recommended as adjunctive therapy because they do not prevent acute rheumatic fever or suppurative complications. 3

Management of Treatment Failure

If initial therapy with amoxicillin or cephalexin fails, prescribe clindamycin 300 mg three times daily for 10 days (adults) or 7 mg/kg three times daily (maximum 300 mg/dose) for 10 days (children). 3

• Clindamycin achieves substantially higher eradication rates than penicillin or amoxicillin in chronic carriers and persistent infections. 3
• Amoxicillin-clavulanate 40 mg/kg/day in 3 doses (maximum 2000 mg amoxicillin/day) for 10 days is an alternative regimen for treatment failures. 1
• Consider whether the patient is a chronic carrier experiencing viral pharyngitis rather than true recurrent streptococcal infections—chronic carriers generally do not require treatment unless special circumstances exist. 3