What is the recommended antibiotic treatment for tonsillitis caused by Group A beta-hemolytic streptococci (GABHS)?

Antibiotic Treatment for Group A Streptococcal Tonsillitis

Penicillin V or amoxicillin for 10 days remains the first-line treatment for Group A beta-hemolytic streptococcal (GABHS) tonsillitis, with penicillin V dosed at 250 mg twice or three times daily in children and 250 mg four times daily or 500 mg twice daily in adolescents and adults. 1

First-Line Treatment for Non-Allergic Patients

Penicillin remains the drug of choice due to its proven efficacy, narrow spectrum, safety profile, and low cost, with no documented penicillin resistance in GABHS anywhere in the world. 1, 2

Recommended Regimens:

• Penicillin V (oral): Children receive 250 mg twice or three times daily; adolescents and adults receive 250 mg four times daily or 500 mg twice daily for 10 days (strong, high-quality evidence). 1
• Amoxicillin (oral): 50 mg/kg once daily (maximum 1000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days (strong, high-quality evidence). 1 Amoxicillin is often preferred in children due to better taste acceptance. 2
• Benzathine penicillin G (intramuscular): <27 kg: 600,000 units; ≥27 kg: 1,200,000 units as a single dose (strong, high-quality evidence). 1

Critical Duration Requirement:

The full 10-day course is essential to achieve maximal pharyngeal eradication of GABHS and prevent acute rheumatic fever—shortening the course by even a few days results in appreciable increases in treatment failure rates. 1, 2, 3

Treatment for Penicillin-Allergic Patients

The choice of alternative antibiotic depends critically on the type of penicillin allergy—this distinction determines whether cephalosporins can be safely used. 4, 3

For Non-Immediate (Non-Anaphylactic) Penicillin Allergy:

First-generation cephalosporins are the preferred first-line alternatives with strong, high-quality evidence supporting their efficacy. 1, 4, 3

• Cephalexin: 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days; adults receive 500 mg twice daily for 10 days. 1, 4, 3
• Cefadroxil: 30 mg/kg once daily (maximum 1 gram) for 10 days. 1, 4, 3

The cross-reactivity risk with first-generation cephalosporins is only 0.1% in patients with non-severe, delayed penicillin reactions. 4

For Immediate/Anaphylactic Penicillin Allergy:

All beta-lactam antibiotics must be avoided due to up to 10% cross-reactivity risk with cephalosporins in patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, respiratory distress, or urticaria occurring within 1 hour). 1, 4, 3

Clindamycin is the preferred alternative for immediate/anaphylactic penicillin allergy:

• Clindamycin: 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days; adults receive 300 mg three times daily for 10 days (strong, moderate-quality evidence). 1, 4, 3
• Clindamycin has approximately 1% resistance rate among GABHS isolates in the United States. 4, 3
• Clindamycin is particularly effective in chronic carriers and patients with recurrent infections due to its superior intracellular penetration and ability to eradicate the organism even in difficult cases. 4, 3, 5

Macrolides are acceptable alternatives but less preferred:

• Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days only due to its prolonged tissue half-life (strong, moderate-quality evidence). 1, 4, 3, 6
• Clarithromycin: 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days (strong, moderate-quality evidence). 1, 4, 3

Critical Resistance Considerations

Macrolide resistance among GABHS varies geographically and temporally, with approximately 5-8% resistance in the United States, making clindamycin or first-generation cephalosporins preferred alternatives in areas with high macrolide resistance. 4, 3 Local resistance patterns should be considered before prescribing macrolides. 4

Azithromycin demonstrated 95% bacteriologic eradication at Day 14 and 77% at Day 30 in clinical trials, compared to 73% and 63% for penicillin V, though approximately 1% of azithromycin-susceptible S. pyogenes isolates became resistant following therapy. 6

Common Pitfalls to Avoid

• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to the 10% cross-reactivity risk. 1, 4, 3
• Do not prescribe shorter courses than recommended (except azithromycin's 5-day regimen)—this leads to treatment failure and increased risk of acute rheumatic fever. 4, 2, 3
• Do not use azithromycin as first-line therapy—it should only be used when penicillin and preferred alternatives cannot be used. 4
• Do not assume all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them. 4
• Avoid aspirin in children due to Reye syndrome risk. 4

Adjunctive Symptomatic Treatment

Acetaminophen or NSAIDs (such as ibuprofen) should be considered for moderate to severe symptoms or high fever. 4, 2, 3 Corticosteroids are not recommended as adjunctive therapy. 4, 2

Management of Treatment Failures

Penicillin treatment failures occur in 5-35% of patients, with beta-lactamase-producing bacteria (BLPB) recovered from over 75% of tonsils in patients with recurrent infection. 7, 8, 5 For patients who fail penicillin therapy, retreatment with the same regimen can be considered if compliance was adequate, or intramuscular benzathine penicillin G if compliance is questionable. 2 Clindamycin or amoxicillin-clavulanate are particularly effective following penicillin failures due to their ability to eradicate BLPB and superior intracellular penetration. 2, 3, 8, 5

Post-Treatment Follow-Up

Routine post-treatment throat cultures or rapid antigen detection tests are not recommended for asymptomatic patients who have completed therapy. 4, 3 Testing should only be considered in special circumstances, such as patients with a history of rheumatic fever. 4, 3