A patient recently treated for streptococcal pharyngitis now presents with a new episode; what is the recommended first‑line antibiotic regimen, and what alternatives should be used if there is a confirmed penicillin allergy?

Recommended Antibiotic Regimen for Recurrent Streptococcal Pharyngitis

For a patient recently treated for strep throat who now presents with a new episode, prescribe the same first‑line antibiotic used initially (penicillin V or amoxicillin for 10 days) unless there is documented treatment failure or concern for chronic carriage. 1

Initial Management Approach

• Confirm the diagnosis with rapid antigen detection testing or throat culture before prescribing antibiotics, because clinical features alone cannot reliably distinguish bacterial from viral pharyngitis 1, 2
• For a single recurrent episode shortly after completing appropriate therapy, any agent listed in standard treatment guidelines is appropriate—including penicillin V, amoxicillin, or intramuscular benzathine penicillin G 1
• Consider intramuscular benzathine penicillin G (600,000 units for <27 kg; 1.2 million units for ≥27 kg) if adherence to oral therapy is questionable, as this ensures complete treatment 1, 3

First‑Line Therapy for Non‑Allergic Patients

• Penicillin V 250 mg orally twice daily for 10 days (children) or 500 mg twice daily for 10 days (adults) remains the gold standard because of zero documented resistance worldwide, narrow spectrum, proven efficacy in preventing rheumatic fever, and low cost 1, 4, 3, 5
• Amoxicillin 50 mg/kg once daily (maximum 1000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days is equally effective and preferred in children because of better palatability 4, 3
• A full 10‑day course is mandatory to achieve maximal pharyngeal eradication and prevent acute rheumatic fever; shortening the course by even a few days markedly increases treatment failure rates 1, 4, 3

Alternatives for Penicillin‑Allergic Patients

Non‑Immediate (Delayed) Penicillin Allergy

• First‑generation cephalosporins are the preferred alternatives with strong, high‑quality evidence: cephalexin 500 mg twice daily or cefadroxil 1 gram once daily for 10 days in adults; cephalexin 20 mg/kg twice daily (maximum 500 mg per dose) for 10 days in children 4, 3
• Cross‑reactivity risk is only 0.1% in patients with delayed, mild penicillin reactions 4, 3

Immediate/Anaphylactic Penicillin Allergy

• Clindamycin is the preferred choice with strong, moderate‑quality evidence: 300 mg orally three times daily for 10 days in adults; 7 mg/kg three times daily (maximum 300 mg per dose) for 10 days in children 4, 3
• Clindamycin resistance is approximately 1% among US Group A Streptococcus isolates and demonstrates superior eradication even in chronic carriers 4, 3
• All β‑lactams must be avoided in patients with immediate hypersensitivity (anaphylaxis, angioedema, urticaria within 1 hour) because cross‑reactivity with cephalosporins can reach 10% 4, 3

Macrolide Options (Less Preferred)

• Azithromycin 500 mg once daily for 5 days (adults) or 12 mg/kg once daily (maximum 500 mg) for 5 days (children) is acceptable when clindamycin cannot be used, but macrolide resistance ranges from 5–8% in the United States 4, 3, 6
• Clarithromycin 250 mg twice daily for 10 days (adults) or 7.5 mg/kg twice daily (maximum 250 mg per dose) for 10 days (children) shares similar resistance concerns 4, 3
• Azithromycin is the only antibiotic requiring just 5 days because of its prolonged tissue half‑life; all other agents require the full 10‑day course 4, 3

Management of True Treatment Failure or Chronic Carriage

• If the patient has documented compliance, confirmed GAS infection, and persistent symptoms after 10 days of penicillin or amoxicillin, switch to one of the following regimens that are substantially more effective at eliminating chronic carriage 1:
  • Clindamycin 20–30 mg/kg/day in 3 doses (maximum 300 mg/dose) for 10 days 1
  • Amoxicillin‑clavulanate 40 mg amoxicillin/kg/day in 3 doses (maximum 2000 mg amoxicillin/day) for 10 days 1
  • Penicillin V plus rifampin: Penicillin V 50 mg/kg/day in 4 doses for 10 days (maximum 2000 mg/day) with rifampin 20 mg/kg/day in 1 dose for the last 4 days (maximum 600 mg/day) 1
  • Benzathine penicillin G plus rifampin: Benzathine penicillin G 600,000 units (<27 kg) or 1.2 million units (≥27 kg) as a single dose, with rifampin 20 mg/kg/day in 2 doses for 4 days (maximum 600 mg/day) 1

Distinguishing Chronic Carriage from Recurrent Infection

• Most patients with frequent discrete episodes are chronic streptococcal carriers experiencing repeated viral infections, not true recurrent GAS pharyngitis 1
• Helpful clues for chronic carriage include: patient age (school‑aged children and adolescents), season, local epidemiological characteristics, and the precise nature of presenting signs and symptoms 1
• Chronic carriers generally do not require antimicrobial therapy unless special circumstances exist (community outbreak of rheumatic fever, family history of rheumatic fever, excessive family anxiety, or tonsillectomy being considered solely for carriage) 1, 3
• Do not order routine post‑treatment throat cultures for asymptomatic patients who have completed therapy; reserve testing for special circumstances such as a history of rheumatic fever 4, 3

Common Pitfalls to Avoid

• 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 4, 3
• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions because of the 10% cross‑reactivity risk 4, 3
• Do not prescribe trimethoprim‑sulfamethoxazole for strep throat; it fails to eradicate GAS in 20–25% of cases 4
• Do not assume all recurrent episodes represent new infections; many are chronic carriers with intercurrent viral illnesses 1

Adjunctive Symptomatic Care

• Offer acetaminophen or ibuprofen for moderate‑to‑severe sore throat, fever, or systemic discomfort 4, 3
• Avoid aspirin in children because of the risk of Reye syndrome 4, 3
• Corticosteroids are not recommended as adjunctive therapy 4, 3