What is the first‑line antibiotic regimen for acute pharyngitis or soft‑tissue infection caused by Streptococcus groups C or G, and what are the recommended alternatives for patients with a penicillin allergy?

Treatment of Group C and Group G Streptococcal Infections

Critical Limitation: Lack of Specific Evidence for Groups C and G

The provided evidence focuses exclusively on Group A Streptococcus (GAS), and there are no guidelines or studies specifically addressing Groups C or G Streptococcus in the evidence base. However, in clinical practice, Groups C and G streptococci are treated similarly to Group A for pharyngitis and soft-tissue infections, using the same antibiotic regimens.

First-Line Treatment for Pharyngitis

For acute pharyngitis caused by Group C or G Streptococcus in patients without penicillin allergy, prescribe penicillin V 500 mg orally twice daily for 10 days or amoxicillin 50 mg/kg once daily (maximum 1000 mg) for 10 days. 1

• Amoxicillin is often preferred due to better palatability and once-daily dosing convenience, with equivalent efficacy to penicillin V. 1
• For patients in whom adherence is uncertain, intramuscular benzathine penicillin G (600,000 units if <27 kg; 1,200,000 units if ≥27 kg) as a single dose ensures compliance. 1

Treatment Algorithm for Penicillin-Allergic Patients

Non-Immediate (Delayed) Penicillin Allergy

For patients with non-immediate penicillin allergy (e.g., delayed rash), first-generation cephalosporins are the preferred alternatives with strong, high-quality evidence. 2, 1

• Cephalexin 500 mg orally twice daily for 10 days (adults) or 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days (children) is the recommended regimen. 1
• Cefadroxil 1 gram once daily for 10 days (adults) or 30 mg/kg once daily (maximum 1 gram) for 10 days (children) is an alternative. 2, 1
• The cross-reactivity risk with first-generation cephalosporins is only 0.1% in patients with non-severe, delayed penicillin reactions. 2

Immediate/Anaphylactic Penicillin Allergy

For patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, urticaria within 1 hour), avoid all beta-lactams including cephalosporins due to up to 10% cross-reactivity risk. 2, 3

• Clindamycin is the preferred choice: 300 mg orally three times daily for 10 days (adults) or 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days (children). 2, 1
• Clindamycin has only approximately 1% resistance among streptococci in the United States and demonstrates high efficacy even in chronic carriers. 2, 3
• Azithromycin 500 mg orally once daily for 5 days (adults) or 12 mg/kg once daily (maximum 500 mg) for 5 days (children) is an acceptable alternative. 2, 1
• Macrolide resistance rates are approximately 5-8% in the United States, making clindamycin more reliable. 2, 3
• Clarithromycin 250 mg orally twice daily for 10 days (adults) or 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days (children) is another option. 2

Treatment of Soft-Tissue Infections

For severe invasive soft-tissue infections such as necrotizing fasciitis or streptococcal toxic shock syndrome caused by any streptococcal group, combination therapy with clindamycin plus penicillin is recommended. 2

• Penicillin 2-4 million units IV every 4-6 hours plus clindamycin 600-900 mg IV every 8 hours provides superior efficacy versus penicillin alone. 2
• Clindamycin suppresses production of streptococcal pyrogenic exotoxins and modulates cytokine production, providing unique benefits beyond antimicrobial activity. 2

Critical Treatment Duration Requirements

All antibiotics except azithromycin require a full 10-day course to achieve maximal pharyngeal eradication and prevent complications. 2, 1, 3

• Azithromycin is the only exception, requiring only 5 days due to its prolonged tissue half-life. 2, 1
• Shortening the course by even a few days results in appreciable increases in treatment failure rates. 1, 3

Common Pitfalls to Avoid

• Do not use cephalosporins in patients who had anaphylaxis, angioedema, or immediate urticaria to penicillin due to 10% cross-reactivity risk. 1, 3
• Do not prescribe trimethoprim-sulfamethoxazole (Bactrim) for streptococcal infections, as it fails to eradicate the organism in 20-25% of cases. 2
• Do not prescribe shorter courses than recommended (except azithromycin's 5-day regimen), as this leads to treatment failure. 1, 3
• Do not assume all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them. 3

Adjunctive Symptomatic Treatment

• Acetaminophen or NSAIDs (such as ibuprofen) should be considered for moderate to severe symptoms or high fever. 2, 1
• Aspirin must be avoided in children due to risk of Reye syndrome. 2, 1
• Corticosteroids are not recommended as adjunctive therapy. 2