What is the first‑line treatment guideline for confirmed Group A streptococcal pharyngitis?

First-Line Treatment for Group A Streptococcal Pharyngitis

Penicillin V 500 mg orally twice daily for 10 days is the first-line treatment for confirmed Group A streptococcal pharyngitis in non-allergic patients. 1

Why Penicillin Remains the Drug of Choice

Penicillin V has proven efficacy, no documented resistance anywhere in the world, narrow antimicrobial spectrum that preserves normal flora, excellent safety profile, and low cost. 1, 2 This makes it superior to broader-spectrum alternatives despite decades of use. 1

• Group A Streptococcus has never developed resistance to penicillin globally, ensuring reliable bactericidal activity. 1, 2
• The narrow spectrum minimizes disruption of protective pharyngeal flora and reduces selection pressure for resistant organisms. 1

Critical Treatment Duration

The full 10-day course is mandatory—shortening therapy by even a few days dramatically increases treatment failure rates and the risk of acute rheumatic fever. 1, 3 This duration is required to achieve maximal pharyngeal eradication and prevent serious complications, even when symptoms resolve within 3-4 days. 1

• Therapy can be safely delayed up to 9 days after symptom onset and still prevent acute rheumatic fever, but once started, the full 10 days must be completed. 2
• The primary goal is preventing acute rheumatic fever and suppurative complications (peritonsillar abscess, cervical lymphadenitis, mastoiditis), not just symptom relief. 1

Alternative First-Line Regimen

Amoxicillin 500 mg orally twice daily (or 25 mg/kg twice daily in children, maximum 500 mg/dose) for 10 days is equally effective and preferred in younger children due to better palatability. 1, 3 Amoxicillin and penicillin V have identical efficacy against Group A Streptococcus. 1

• Once-daily amoxicillin dosing (750-1000 mg daily in adults, 40-50 mg/kg daily in children) is also effective and may improve adherence. 1, 3, 4

For Patients with Penicillin Allergy

Non-Immediate (Delayed) Reactions

First-generation cephalosporins such as cephalexin 500 mg twice daily for 10 days are the preferred alternatives, with only 0.1% cross-reactivity risk in patients with non-anaphylactic penicillin allergy. 1, 2 These agents have strong, high-quality evidence supporting their efficacy. 1

Immediate/Anaphylactic Reactions

Clindamycin 300 mg orally three times daily for 10 days is the preferred choice for patients with immediate hypersensitivity to penicillin, with approximately 1% resistance among Group A Streptococcus in the United States. 1, 2 Patients with anaphylaxis, angioedema, or urticaria within 1 hour of penicillin exposure must avoid all beta-lactam antibiotics due to up to 10% cross-reactivity. 1, 2

• Azithromycin 500 mg once daily for 5 days is an acceptable alternative but has 5-8% macrolide resistance rates in the United States. 1, 2
• Clarithromycin 250 mg twice daily for 10 days is also acceptable but shares the same resistance concerns as azithromycin. 1, 2

For Patients with Compliance Concerns

A single intramuscular dose of benzathine penicillin G is an effective alternative when adherence to oral therapy is questionable. 1 This ensures complete treatment delivery and eliminates compliance issues. 1

Common Pitfalls to Avoid

• Do not prescribe antibiotics without microbiologic confirmation (positive rapid antigen test or throat culture), as clinical diagnosis alone has insufficient accuracy (≤80% predictive value). 1
• Do not use trimethoprim-sulfamethoxazole (Bactrim) for streptococcal pharyngitis—it fails to eradicate Group A Streptococcus in 20-25% of cases and is absolutely contraindicated. 2
• Do not prescribe broad-spectrum cephalosporins (cefuroxime, cefdinir, cefpodoxime) when narrow-spectrum first-generation agents are appropriate—they are more expensive and promote resistant flora. 2
• Do not order routine post-treatment throat cultures in asymptomatic patients who have completed therapy—these are not recommended except in special circumstances such as history of rheumatic fever. 1
• Do not treat asymptomatic household contacts—approximately 25% may harbor Group A Streptococcus but are at low risk for complications. 1

Expected Clinical Response

• Fever should resolve within 48 hours of initiating therapy in uncomplicated cases. 1
• Clinical improvement is expected within 24-48 hours. 1
• Microbiologic failure rates of 10-20% are expected even with optimal penicillin therapy. 1