In an otherwise healthy adult with laboratory-confirmed group A streptococcal pharyngitis, what is the recommended antibiotic treatment and the alternatives for penicillin-allergic patients?

Antibiotic Treatment for Group A Streptococcal Pharyngitis in Adults

For an otherwise healthy adult with laboratory-confirmed group A streptococcal pharyngitis, prescribe penicillin V 500 mg orally twice daily (or 250 mg four times daily) for a full 10 days, or amoxicillin 50 mg/kg once daily (maximum 1000 mg) for 10 days. 1, 2, 3

Why Penicillin Remains First-Line

• Penicillin V is the drug of choice because no documented penicillin resistance exists anywhere in the world among Group A Streptococcus, ensuring reliable bacterial eradication. 1, 2
• Penicillin offers proven efficacy in preventing acute rheumatic fever, has a narrow antimicrobial spectrum (minimizing collateral damage to normal flora), excellent safety profile, and low cost. 1, 3, 4
• Amoxicillin is equally effective and may enhance adherence due to once-daily dosing, making it an acceptable alternative to penicillin V. 1, 3

The Full 10-Day Course Is Mandatory

• Completing the entire 10-day regimen is essential to achieve maximal pharyngeal eradication and prevent acute rheumatic fever, even when symptoms resolve within 3–4 days. 1, 2, 3
• Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk. 1, 2
• Antibiotics shorten symptom duration by only 1–2 days, but the primary goal is preventing serious complications—not just symptom relief. 1

Alternatives for Penicillin-Allergic Patients

Non-Immediate (Delayed) Penicillin Allergy

• First-generation cephalosporins are the preferred alternatives for patients with delayed, mild penicillin reactions (e.g., rash occurring > 1 hour after exposure). 1, 3
• Cephalexin 500 mg orally twice daily for 10 days is recommended, with strong, high-quality evidence supporting narrow-spectrum activity, proven efficacy, and essentially zero resistance. 1, 2
• Cefadroxil 1 gram orally once daily for 10 days is equally effective. 1, 2
• The cross-reactivity risk with first-generation cephalosporins is only 0.1% in patients with non-severe, delayed penicillin reactions. 1

Immediate/Anaphylactic Penicillin Allergy

• All beta-lactam antibiotics must be avoided in patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, respiratory distress, or urticaria within 1 hour of penicillin exposure) due to up to 10% cross-reactivity risk. 1, 3
• Clindamycin 300 mg orally three times daily for 10 days is the preferred choice, with only approximately 1% resistance among U.S. Group A Streptococcus isolates and superior eradication rates even in chronic carriers. 1, 2, 3
• Azithromycin 500 mg once daily for 5 days is an acceptable alternative, but macrolide resistance ranges from 5–8% in the United States and varies geographically. 1, 5, 6
• Clarithromycin 250 mg twice daily for 10 days is another macrolide option with similar resistance concerns. 1, 2
• 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. 1, 5

Critical Pitfalls to Avoid

• Do not prescribe cephalosporins to patients with immediate/anaphylactic penicillin reactions—the 10% cross-reactivity risk makes all beta-lactams unsafe in this group. 1, 3
• Do not shorten the antibiotic course below 10 days (except azithromycin's 5-day regimen), as this dramatically increases treatment failure and rheumatic fever risk. 1, 2, 3
• Do not use trimethoprim-sulfamethoxazole (Bactrim) for streptococcal pharyngitis—sulfonamides fail to eradicate Group A Streptococcus in 20–25% of cases. 1
• Do not prescribe broad-spectrum antibiotics when narrow-spectrum penicillin is appropriate—this unnecessarily increases cost and promotes antibiotic-resistant flora. 1, 3

Adjunctive Symptomatic Management

• Offer acetaminophen or NSAIDs (e.g., ibuprofen) for moderate to severe sore throat, fever, or systemic discomfort. 1, 3
• Avoid aspirin in younger patients due to Reye syndrome risk. 1, 3
• Corticosteroids are not recommended as adjunctive therapy. 1

When to Consider Alternative Diagnoses

• If symptoms do not improve within 48–72 hours of appropriate antibiotic therapy, reassess the diagnosis and consider non-compliance, treatment failure, or alternative etiologies. 1
• Routine post-treatment throat cultures are not recommended for asymptomatic patients who have completed therapy; reserve testing for special circumstances such as history of rheumatic fever. 1, 3

Addressing the Question About "Not Prescribing Antibiotics"

• Research shows that in unselected adults with pharyngitis (most of whom have viral infections), antibiotics provide minimal benefit and are often unnecessary. 4, 7
• However, for laboratory-confirmed Group A streptococcal pharyngitis, antibiotics are clearly indicated to prevent acute rheumatic fever and suppurative complications. 4, 8, 9
• The key is proper patient selection: use clinical scoring (Centor criteria) and rapid antigen testing to identify the 10% of adults with true streptococcal infection who benefit from antibiotics. 4
• Delayed antibiotic prescribing (starting only if symptoms persist after 48 hours) may reduce antibiotic use by 85% in unselected pharyngitis cases without increasing complications, but this strategy does not apply to confirmed streptococcal pharyngitis. 7