In an otherwise healthy adult with confirmed group A streptococcal pharyngitis, what is the recommended antibiotic regimen, including first‑line drug, dosage, duration, and alternatives for penicillin allergy?

Antibiotic Treatment for Strep Throat

For an otherwise healthy adult with confirmed Group A streptococcal pharyngitis, prescribe penicillin V 500 mg orally twice daily for 10 days, or amoxicillin 50 mg/kg once daily (maximum 1 gram) for 10 days. 1, 2

First-Line Therapy for Non-Allergic Patients

• Penicillin V or amoxicillin for 10 days is the definitive first-line regimen, offering narrow-spectrum activity, proven efficacy in preventing acute rheumatic fever, excellent safety, and low cost. 1, 3

• Specific dosing:

  • Penicillin V: 250 mg orally 2–3 times daily for adults (500 mg twice daily is also acceptable). 2, 1
  • Amoxicillin: 50 mg/kg once daily (maximum 1 gram) for 10 days. 1, 3

• No documented penicillin resistance exists in Group A Streptococcus worldwide, ensuring reliable efficacy. 3

• Intramuscular benzathine penicillin G (1.2 million units single dose) should be used when compliance with oral therapy is questionable. 1, 3

Treatment Duration: Non-Negotiable 10 Days

• A full 10-day course is mandatory for all antibiotics (except azithromycin) to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever. 1, 3

• Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk, even if symptoms resolve within 3–4 days. 1, 3

• Therapy initiated within 9 days of symptom onset still effectively prevents acute rheumatic fever. 3, 4

Alternatives for Penicillin Allergy

Non-Immediate (Delayed) Penicillin Allergy

• First-generation cephalosporins are the preferred alternative, with strong, high-quality evidence supporting their efficacy. 1, 3

• Cephalexin 500 mg orally twice daily for 10 days is the recommended regimen. 5, 3

• Cefadroxil 1 gram orally once daily for 10 days is equally effective. 1, 3

• Cross-reactivity risk with first-generation cephalosporins is only 0.1% in patients with non-immediate penicillin reactions. 1, 3

Immediate/Anaphylactic Penicillin Allergy

• All beta-lactams (including cephalosporins) must be avoided because cross-reactivity can be up to 10%. 1, 3

• Clindamycin 300 mg orally three times daily for 10 days is the preferred beta-lactam-free alternative, with only approximately 1% resistance among U.S. Group A Streptococcus isolates and superior eradication rates even in chronic carriers. 1, 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, 3

• Clarithromycin 250 mg orally twice daily for 10 days is another macrolide option with similar resistance concerns. 1, 3

• Azithromycin is the only antibiotic that requires just 5 days due to its prolonged tissue half-life; all other agents require the full 10-day course. 1, 3

Symptomatic Management

• Offer acetaminophen or NSAIDs (e.g., ibuprofen) for moderate to severe sore throat, fever, or systemic discomfort. 1, 3

• Avoid aspirin in children due to the risk of Reye syndrome. 1, 3

• Corticosteroids are not recommended as adjunctive therapy. 1, 3

• Antibiotics shorten symptom duration by only 1–2 days, but are critical for preventing acute rheumatic fever and suppurative complications. 4, 6

Clinical Response Timeline

• Patients typically experience noticeable clinical improvement within 24–48 hours of starting antibiotics. 1

• Patients are no longer contagious after 24 hours of appropriate antibiotic therapy. 1

• Symptoms typically resolve within less than 1 week even without antibiotics, but the primary goal of treatment is preventing acute rheumatic fever, not just symptom relief. 1, 4

Common Pitfalls to Avoid

• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to the 10% cross-reactivity risk. 1, 3

• Do not prescribe azithromycin as first-line therapy; it should only be used when penicillin and preferred alternatives cannot be used. 1, 3

• Do not ignore local macrolide resistance patterns, as resistance varies geographically and can lead to treatment failure. 1, 3

• Do not prescribe broad-spectrum cephalosporins (e.g., cefdinir, cefpodoxime) when narrow-spectrum first-generation agents are appropriate, as they are more expensive and promote antibiotic resistance. 3

• Do not perform routine follow-up throat cultures or rapid tests after completing therapy in asymptomatic patients; positive post-treatment tests often reflect carrier status rather than treatment failure. 1, 3

• Do not test or treat asymptomatic household contacts; up to one-third may be asymptomatic carriers, and prophylactic treatment does not reduce subsequent infection rates. 3, 4

Special Considerations

• Chronic carriers generally do not require treatment, as they are unlikely to spread infection or develop complications. 1, 3

• For treatment failures or chronic carriers, clindamycin demonstrates substantially higher eradication rates than penicillin or amoxicillin. 3

• Follow-up testing should only be considered in special circumstances, such as patients with a history of rheumatic fever. 1, 3