What are the first‑line antibiotics for acute bacterial tonsillitis and the alternative regimens for patients with penicillin allergy or who are pregnant?

Antibiotics for Tonsillitis

First-Line Treatment for Non-Allergic Patients

Penicillin V or amoxicillin for 10 days is the gold-standard treatment for acute bacterial tonsillitis caused by Group A Streptococcus. 1

• Amoxicillin 50 mg/kg once daily (maximum 1000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days is preferred in children due to better palatability and more convenient dosing 1
• Adults: Penicillin V 500 mg orally twice daily for 10 days 1
• Children ≥27 kg: Penicillin V 500 mg twice daily for 10 days 1
• Children <27 kg: Penicillin V 250 mg twice daily for 10 days 1
• Zero documented penicillin resistance exists worldwide among Group A Streptococcus, guaranteeing reliable bacterial eradication 1

Critical Treatment Duration

A complete 10-day course is mandatory for all antibiotics (except azithromycin) to achieve maximal pharyngeal eradication and prevent acute rheumatic fever. 1

• Shortening the course by even 2–3 days markedly increases treatment failure rates and rheumatic fever risk 1
• The primary goal is preventing acute rheumatic fever and suppurative complications, not just symptom relief 1
• Symptoms typically resolve within 3–4 days, but premature discontinuation permits bacterial regrowth 1

Treatment for Penicillin-Allergic Patients

Non-Immediate (Delayed) Penicillin Allergy

First-generation cephalosporins are the preferred alternative for patients with delayed, mild penicillin reactions (e.g., rash occurring >1 hour after exposure). 2

• Cephalexin 500 mg twice daily for 10 days (adults) or 20 mg/kg twice daily (maximum 500 mg per dose) for 10 days (children) 2
• Cefadroxil 1 g once daily for 10 days (adults) or 30 mg/kg once daily (maximum 1 g) for 10 days (children) 2
• Cross-reactivity risk is only 0.1% with first-generation cephalosporins in delayed reactions 2
• Strong, high-quality evidence supports their efficacy, with essentially 0% resistance 2

Immediate/Anaphylactic Penicillin Allergy

Clindamycin is the preferred alternative for patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, respiratory distress, or urticaria within 1 hour of penicillin). 2

• Clindamycin 300 mg orally three times daily for 10 days (adults) 2
• Clindamycin 7 mg/kg three times daily (maximum 300 mg per dose) for 10 days (children) 2
• All β-lactam antibiotics must be avoided due to up to 10% cross-reactivity risk 2
• Clindamycin resistance is only ~1% among US Group A Streptococcus isolates 2
• Superior eradication rates even in chronic carriers and treatment failures 3

Macrolide Alternatives (Less Preferred)

Macrolides are acceptable alternatives but less preferred due to 5–8% resistance rates in the United States. 2

• Azithromycin 500 mg once daily for 5 days (adults) or 12 mg/kg once daily (maximum 500 mg) for 5 days (children) 2
• Azithromycin is the only antibiotic requiring just 5 days due to its prolonged tissue half-life 2
• 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) 2
• Macrolide resistance varies geographically and can be much higher in some regions 2

Treatment for Pregnant Patients

For pregnant women requiring intrapartum antibiotic prophylaxis for Group B Streptococcus with non-immediate penicillin allergy, cefazolin is recommended. 2

• Cefazolin 2 grams IV initial dose, then 1 gram IV every 8 hours until delivery 2
• For immediate/anaphylactic penicillin allergy with susceptible isolate: Clindamycin 900 mg IV every 8 hours until delivery 2

Management of Treatment Failure

If symptoms persist after a fully adhered 10-day course of amoxicillin or penicillin, switch to clindamycin. 3

• Clindamycin 300 mg three times daily for 10 days demonstrates substantially higher eradication rates than repeating penicillin 3
• Amoxicillin-clavulanate 40 mg amoxicillin/kg/day in three divided doses for 10 days is an acceptable alternative for chronic carriers 3
• The clavulanate component inhibits β-lactamases produced by co-colonizing oral flora that can shield Group A Streptococcus 4

Common Pitfalls to Avoid

• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to ~10% cross-reactivity risk 2
• Do not shorten the antibiotic course below 10 days (except azithromycin's 5-day regimen), as this dramatically increases failure and rheumatic fever risk 1
• Do not prescribe trimethoprim-sulfamethoxazole for strep throat; it fails to eradicate Group A Streptococcus in 20–25% of cases 1
• Do not use tetracyclines for streptococcal pharyngitis; they fail to eradicate the organism and do not prevent acute rheumatic fever 1
• Do not order routine post-treatment throat cultures for asymptomatic patients who completed therapy; reserve testing for special circumstances like history of rheumatic fever 1

Adjunctive Symptomatic Management

• Acetaminophen or ibuprofen may be offered for moderate-to-severe sore throat, fever, or systemic discomfort 1
• Avoid aspirin in children due to the risk of Reye syndrome 1
• Corticosteroids are not recommended as adjunctive therapy for streptococcal pharyngitis 1