What is the appropriate penicillin dosage for an otherwise healthy adult with Group A streptococcal pharyngitis?

Penicillin Dosing for Adult Streptococcal Pharyngitis

For an otherwise healthy adult with confirmed Group A streptococcal pharyngitis, prescribe penicillin V 500 mg orally twice daily for a full 10 days. 1

First-Line Treatment Regimen

• Penicillin V remains the drug of choice for adults with strep throat due to its proven efficacy, narrow antimicrobial spectrum, excellent safety profile, and low cost. 1, 2
• The recommended dosing is penicillin V 500 mg orally twice daily (or 250 mg four times daily) for 10 days. 1
• No documented penicillin resistance exists anywhere in the world among Group A Streptococcus, ensuring reliable bacterial eradication. 1, 2

Why the Full 10-Day Course Is Mandatory

• A complete 10-day course is essential to achieve maximal pharyngeal eradication of Group A Streptococcus and to prevent acute rheumatic fever, even if symptoms resolve within 3–4 days. 1, 2
• Shortening the course by even a few days leads to appreciable increases in treatment failure rates (31% failure with 7 days versus 18% with 10 days) and increases the risk of acute rheumatic fever. 1, 3
• The primary goal is preventing acute rheumatic fever and suppurative complications, not just symptom relief—this requires adequate bacterial eradication that only a full 10-day course provides. 1

Alternative: Intramuscular Benzathine Penicillin G

• For adults in whom compliance with oral therapy is questionable, intramuscular benzathine penicillin G 1.2 million units as a single dose is preferred. 1, 4
• This single injection ensures complete treatment and eliminates adherence concerns. 4
• The injection should be administered by deep intramuscular injection in the upper, outer quadrant of the buttock (dorsogluteal) or ventrogluteal site. 4

Amoxicillin as an Acceptable Alternative

• Amoxicillin 500 mg twice daily for 10 days is an acceptable alternative with comparable efficacy to penicillin V. 1
• Amoxicillin and penicillin V have identical efficacy against Group A Streptococcus, though amoxicillin may be preferred for better palatability. 1, 2

Treatment for Penicillin-Allergic Patients

Non-Immediate (Delayed) Penicillin Allergy

• First-generation cephalosporins are the preferred alternatives with strong, high-quality evidence, as the cross-reactivity risk is only 0.1% in patients with delayed, mild reactions. 1, 5
• Prescribe cephalexin 500 mg orally twice daily for 10 days or cefadroxil 1 gram once daily for 10 days. 1, 5

Immediate/Anaphylactic Penicillin Allergy

• All beta-lactam antibiotics must be avoided (including cephalosporins) due to up to 10% cross-reactivity risk in patients with anaphylaxis, angioedema, or urticaria within 1 hour of penicillin exposure. 1, 5
• Clindamycin 300 mg orally three times daily for 10 days is the preferred choice, with only ~1% resistance among U.S. Group A Streptococcus isolates and demonstrated high efficacy even in chronic carriers. 1, 5
• Azithromycin 500 mg once daily for 5 days is an acceptable alternative, though macrolide resistance ranges from 5–8% in the United States. 1, 5
• Clarithromycin 250 mg twice daily for 10 days is another macrolide option with similar resistance concerns. 1, 5

Common Pitfalls to Avoid

• Do not prescribe shorter courses than 10 days (except azithromycin's 5-day regimen due to its unique pharmacokinetics), as this dramatically increases treatment failure and rheumatic fever risk. 1, 2
• Do not use cephalosporins in patients who had anaphylaxis, angioedema, or immediate urticaria to penicillin due to the 10% cross-reactivity risk. 1, 5
• Do not prescribe antibiotics without confirming Group A Streptococcus infection via rapid antigen detection test or throat culture, as most pharyngitis cases are viral. 6
• 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. 1

Adjunctive Symptomatic Treatment

• Offer acetaminophen or NSAIDs (such as ibuprofen) for moderate to severe sore throat or high fever. 1, 2
• Corticosteroids are not recommended as adjunctive therapy. 5