What is the treatment of choice for Group A Streptococcus (GAS) infections?

Treatment of Group A Streptococcus (GAS) Infections

Penicillin (either oral penicillin V or intramuscular benzathine penicillin G) is the treatment of choice for GAS pharyngitis due to its proven efficacy in preventing rheumatic fever, narrow spectrum of activity, low cost, and the complete absence of documented penicillin resistance in GAS. 1, 2

First-Line Treatment Regimens

For Non-Allergic Patients

Oral Options:

• Penicillin V: 250 mg two to three times daily for children, or 250 mg four times daily or 500 mg twice daily for adolescents and adults, for 10 days 2
• Amoxicillin: 50 mg/kg once daily (maximum 1,000 mg) or 25 mg/kg twice daily (maximum 500 mg) for 10 days 2
  • Amoxicillin is equally effective as penicillin V and may enhance adherence due to once-daily dosing 3
  • Higher-dose amoxicillin (40 mg/kg/day) demonstrates superior clinical cure (87.9% vs 70.9%) and bacteriologic cure (79.3% vs 54.5%) compared to standard-dose penicillin V 4

Injectable Option:

• Benzathine penicillin G (single intramuscular dose): 600,000 units for patients <60 lb (27 kg) or 1,200,000 units for patients ≥60 lb 2
  • This is the preferred option for patients unlikely to complete a full 10-day oral course 2

Critical Treatment Duration

All antibiotics except azithromycin require a full 10-day course to achieve maximal pharyngeal eradication and prevent acute rheumatic fever. 2, 5 Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk 5. Therapy can be safely postponed up to 9 days after symptom onset and still prevent acute rheumatic fever 5.

Treatment Algorithm for Penicillin-Allergic Patients

Step 1: Determine Type of Allergy

Non-immediate (delayed) reactions include rash occurring >1 hour after administration 5

Immediate/anaphylactic reactions include anaphylaxis, angioedema, respiratory distress, or urticaria occurring within 1 hour 5

Step 2: Select Appropriate Alternative

For Non-Immediate Penicillin Allergy:

• First-generation cephalosporins are preferred (cross-reactivity risk only 0.1%) 5
  • Cephalexin: 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days 5
  • Cefadroxil: 30 mg/kg once daily (maximum 1 gram) for 10 days 5
• These have strong, high-quality evidence for efficacy and are preferred over broad-spectrum cephalosporins 2, 3

For Immediate/Anaphylactic Penicillin Allergy (avoid ALL beta-lactams):

• Clindamycin is the preferred choice (resistance rate ~1% in US) 2, 5

  • Dosing: 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days 2, 5
  • Particularly effective in chronic carriers who have failed penicillin treatment 5

• Macrolide alternatives (resistance rate 5-8% in US, varies geographically) 2, 5:

  • Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days only 2, 5
  • Clarithromycin: 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days 5
  • Erythromycin: 20-40 mg/kg/day divided 2-3 times daily for 10 days (less preferred due to GI side effects) 5

Critical Pitfall: Cephalosporin Cross-Reactivity

Up to 10% of patients with immediate penicillin hypersensitivity have cross-reactivity with cephalosporins, making all beta-lactams unsafe in this group 5. Do not prescribe cephalosporins to patients with anaphylaxis, angioedema, or immediate urticaria to penicillin 5.

Why Penicillin Remains Superior

Despite reports of increasing treatment failure rates (now approximately 30% compared to 2-10% before the 1970s), penicillin remains the treatment of choice because 1, 6, 7:

• No documented penicillin resistance in GAS anywhere in the world 1, 5
• Proven efficacy in preventing rheumatic fever (the primary goal of treatment) 1, 6
• Treatment failures are primarily due to non-compliance with the 10-day regimen, reexposure to infected contacts, or chronic carrier states—not true antibiotic resistance 7

Adjunctive Therapy

• Acetaminophen or NSAIDs for moderate to severe symptoms or high fever 2, 5
• Avoid aspirin in children due to Reye syndrome risk 2, 5
• Corticosteroids are not recommended 2, 5

Special Considerations

Chronic Carriers

• Generally do not require antimicrobial therapy as they are unlikely to spread GAS pharyngitis and are at little risk for complications 5
• If treatment is needed, clindamycin or amoxicillin/clavulanate are most effective 2, 5

Recurrent Pharyngitis

• Retreatment with the same agent used initially 2
• Intramuscular benzathine penicillin G if compliance with oral therapy is questionable 2
• Consider clindamycin or amoxicillin/clavulanate for chronic carriers 2

Post-Treatment Testing

Routine post-treatment throat cultures are not recommended for asymptomatic patients who have completed therapy 2, 5. Testing should only be considered in special circumstances, such as patients with a history of rheumatic fever 5.

Common Pitfalls to Avoid

• Do not prescribe shorter courses than recommended (except azithromycin's 5-day regimen), as this dramatically increases treatment failure and rheumatic fever risk 2, 5
• Do not use broad-spectrum cephalosporins (cefixime, cefuroxime, cefdinir) when narrow-spectrum agents are appropriate, as they unnecessarily select for antibiotic-resistant flora 3
• Do not assume all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them 5
• Do not use trimethoprim-sulfamethoxazole (Bactrim) for strep throat due to high resistance rates (50%) and lack of efficacy against GAS 5
• Do not overtreat likely viral pharyngitis (presenting with cough, rhinorrhea, hoarseness, oral ulcers) with antibiotics 2