What are the first‑generation penicillins and the recommended regimen for a patient with a confirmed Group A Streptococcus throat infection?

First-Generation Penicillins for Group A Streptococcal Pharyngitis

First-generation penicillins include penicillin V (oral) and benzathine penicillin G (intramuscular), which remain the drugs of choice for treating confirmed Group A Streptococcal throat infections due to zero documented resistance worldwide, narrow antimicrobial spectrum, proven efficacy in preventing acute rheumatic fever, excellent safety profile, and low cost. 1, 2

Recommended Regimens for Confirmed GAS Pharyngitis

Oral Penicillin V (First-Line)

• Adults and adolescents: 250 mg orally 3–4 times daily or 500 mg twice daily for 10 days 1, 3
• Children ≥27 kg: 500 mg twice daily for 10 days 3
• Children <27 kg: 250 mg 2–3 times daily for 10 days 1, 3

Intramuscular Benzathine Penicillin G (When Adherence Is Uncertain)

• Weight ≥27 kg (60 lbs): 1.2 million units IM as a single dose 1, 3
• Weight <27 kg (60 lbs): 600,000 units IM as a single dose 1, 3

Amoxicillin (Preferred in Young Children)

• Amoxicillin is often substituted for penicillin V in children because of better palatability and more convenient dosing, while providing identical efficacy 1, 3, 2
• Dosing: 50 mg/kg once daily (maximum 1000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days 3, 2
• Higher-dose amoxicillin (40–50 mg/kg/day) achieves superior clinical cure (≈88% vs 71%) and bacteriologic eradication (≈79% vs 55%) compared with lower-dose penicillin V 4

Critical Treatment Duration

• A complete 10-day course is mandatory for all penicillin regimens to achieve maximal pharyngeal eradication of Group A Streptococcus and to prevent acute rheumatic fever 1, 3, 2
• Shortening the course by even 2–3 days markedly increases treatment-failure rates and rheumatic fever risk, even when symptoms resolve within 3–4 days 1, 3, 2
• Therapy can be safely postponed up to 9 days after symptom onset and still prevent acute rheumatic fever, allowing time for diagnostic confirmation 1, 3

Why First-Generation Penicillins Remain First-Line

• Zero documented penicillin resistance exists worldwide among Group A Streptococcus, guaranteeing reliable bacterial eradication 3, 2, 5
• Penicillin is the only antibiotic with proven efficacy in controlled trials for preventing initial attacks of acute rheumatic fever 1, 5
• The narrow antimicrobial spectrum minimizes selection of resistant flora compared with broader-spectrum agents 3, 2
• Penicillin has the lowest cost among all recommended antibiotics 3, 2

Common Pitfalls to Avoid

• Do not prescribe courses shorter than 10 days based on clinical improvement; premature discontinuation permits bacterial regrowth and symptom relapse 1, 3, 2
• Do not use broad-spectrum antibiotics when narrow-spectrum penicillin is appropriate, as they unnecessarily promote resistant flora and increase cost 1, 3
• Do not order routine post-treatment throat cultures for asymptomatic patients who completed therapy; reserve testing for special circumstances such as history of rheumatic fever 1, 3