What is the recommended antibiotic regimen for presumed bacterial tonsillitis in a healthy adult and in children, and what alternatives are appropriate for patients with a penicillin allergy?

Antibiotic Treatment for Bacterial Tonsillitis

First-Line Treatment

Penicillin V (phenoxymethylpenicillin) or amoxicillin for 10 days is the recommended first-line antibiotic treatment for presumed bacterial tonsillitis in both adults and children. 1

Adults

• Penicillin V: 250 mg four times daily OR 500 mg twice daily for 10 days 1
• Amoxicillin: 500 mg twice daily for 10 days (alternative dosing with equivalent efficacy) 1

Children

• Penicillin V: 250 mg twice or three times daily for 10 days 1
• Amoxicillin: 50 mg/kg once daily (maximum 1000 mg) OR 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days 1

Rationale: Penicillin and amoxicillin remain the gold standard due to their narrow spectrum of activity, proven efficacy in preventing rheumatic fever and suppurative complications, excellent safety profile, and low cost. 1 Group A streptococcus has never developed resistance to penicillin. 1

Alternative: Single-Dose Intramuscular Option

• Benzathine penicillin G (intramuscular): <27 kg: 600,000 units; ≥27 kg: 1,200,000 units as a single dose 1
• This option ensures complete compliance but is more invasive 1

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Treatment for Penicillin-Allergic Patients

Non-Severe Penicillin Allergy (e.g., rash without anaphylaxis)

First-generation cephalosporins are the preferred alternative for patients with non-Type I hypersensitivity reactions:

Adults and Children

• Cephalexin: 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days 1
• Cefadroxil: 30 mg/kg once daily (maximum 1 g) for 10 days 1

Important caveat: Cephalosporins should be avoided in patients with immediate Type I hypersensitivity reactions (anaphylaxis, angioedema, urticaria) to penicillin due to potential cross-reactivity. 1

Severe Penicillin Allergy (Type I Hypersensitivity)

For patients with documented severe penicillin allergy, macrolides are recommended despite higher failure rates:

Adults and Children

• Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days 1, 2
• Clarithromycin: 7.5 mg/kg per dose twice daily (maximum 250 mg per dose) for 10 days 1
• Clindamycin: 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days 1

Critical limitation: Macrolide resistance in Group A streptococcus varies geographically and temporally, with bacteriologic failure rates of 20-25% possible. 1 In regions with high macrolide resistance, cephalexin is preferred if the allergy is not severe. 1

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Duration of Therapy Considerations

Standard 10-day penicillin therapy remains the benchmark, though some alternatives exist: 1

• High-dose penicillin (four times daily) for 5 days showed non-inferiority to standard 10-day therapy (89.6% vs 93.3% clinical cure), but with lower bacterial eradication rates 1
• Short-course cephalosporins (5 days) demonstrated better microbial eradication than 10-day penicillin therapy 1
• Azithromycin requires only 5 days due to prolonged tissue half-life 1, 2

Clinical pearl: While 5-day courses of standard-dose penicillin show inferior bacteriologic eradication (OR 0.43; 95% CI 0.23-0.82), this approach cannot be recommended given the inability to assess rare but serious complications like rheumatic fever in modern studies. 1

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Common Pitfalls to Avoid

• Do not routinely prescribe antibiotics without confirmation: Viral pharyngitis is far more common than bacterial, and clinical features like cough, rhinorrhea, hoarseness, and oral ulcers strongly suggest viral etiology. 1
• Avoid routine skin testing for penicillin allergy: This is unnecessary before first exposure and is not current best practice. 1
• Do not use macrolides as first-line therapy: Reserve these for true penicillin allergy due to increasing resistance patterns. 1
• Avoid fluoroquinolones: These are not indicated for routine tonsillitis and should be reserved for resistant infections. 1
• Do not prescribe TMP/SMX: This has inconsistent activity against pneumococci and high failure rates (20-25%). 1

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When to Reassess

Failure to respond after 72 hours of appropriate antibiotic therapy warrants either switching to alternative antimicrobial therapy or clinical reevaluation. 1 Consider suppurative complications (peritonsillar abscess, cervical lymphadenitis) or alternative diagnoses if symptoms persist or worsen despite treatment. 1