Treatment of Streptococcal Infections in Penicillin-Allergic Patients
For patients with non-immediate penicillin allergy, use first-generation cephalosporins (cephalexin 500 mg twice daily or cefadroxil 1 gram once daily for 10 days); for patients with immediate/anaphylactic penicillin allergy, use clindamycin 300 mg three times daily for 10 days or azithromycin 500 mg once daily for 5 days. 1, 2
Treatment Algorithm Based on Allergy Type
Non-Immediate Penicillin Allergy (No History of Anaphylaxis, Angioedema, or Urticaria)
First-generation cephalosporins are the preferred first-line alternative with strong, high-quality evidence supporting their use. 3, 1, 2
- Cephalexin 500 mg twice daily for 10 days (pediatric: 20 mg/kg per dose twice daily, maximum 500 mg/dose) 1, 2
- Cefadroxil 1 gram once daily for 10 days (pediatric: 30 mg/kg once daily, maximum 1 gram) 1, 2
- Narrow-spectrum first-generation cephalosporins are strongly preferred over broad-spectrum agents to minimize selection of antibiotic-resistant flora 3
Immediate/Anaphylactic Penicillin Allergy
Avoid all beta-lactams including cephalosporins due to up to 10% cross-reactivity risk in patients with immediate hypersensitivity reactions. 3, 1, 2
Clindamycin is the preferred alternative with strong, moderate-quality evidence:
- Adult dose: 300 mg three times daily for 10 days 1, 2
- Pediatric dose: 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days 1
- Clindamycin resistance among Group A Streptococcus in the United States is approximately 1%, making this an excellent choice 3, 1
- Particularly effective in chronic carriers and treatment failures due to superior pharyngeal penetration 1, 4
Macrolides are acceptable alternatives with strong, moderate-quality evidence but carry resistance concerns:
- Azithromycin 500 mg once daily for 5 days (pediatric: 12 mg/kg once daily, maximum 500 mg) 3, 1, 5
- Clarithromycin 250 mg twice daily for 10 days (pediatric: 7.5 mg/kg per dose twice daily, maximum 250 mg/dose) 3, 1
- Erythromycin 500 mg 2-3 times daily for 10 days (pediatric: 20-40 mg/kg/day divided 2-3 times daily) - associated with substantially higher gastrointestinal side effects 3, 6
Critical Treatment Duration Requirements
All antibiotics require a full 10-day course except azithromycin, which requires only 5 days due to its prolonged tissue half-life. 3, 1, 2, 5, 7
- Completing the full 10-day course is essential to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever 1, 2, 4
- Azithromycin's unique pharmacokinetics allow for the shortened 5-day regimen with comparable efficacy to 10-day penicillin courses 5, 8, 7
Important Resistance Patterns and Efficacy Considerations
Macrolide resistance among Group A Streptococcus varies geographically, with approximately 5-8% resistance in most areas of the United States in recent years. 3, 1
- Be aware of local resistance patterns before prescribing macrolides, as resistance can be highly prevalent in some regions 3, 1, 4
- One study suggests 10 days of clarithromycin may be more effective than 5 days of azithromycin in eradicating Group A Streptococcus 3
- Clindamycin resistance remains low at approximately 1% in the United States, making it highly reliable 3, 1
Common Pitfalls to Avoid
Do not use cephalosporins in patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, urticaria) to penicillin due to 10% cross-reactivity risk. 3, 1, 2
Do not prescribe shorter courses than recommended (except azithromycin's 5-day regimen), as this leads to treatment failure and increased risk of acute rheumatic fever. 1, 2
Do not assume all penicillin-allergic patients cannot receive cephalosporins - only those with immediate/anaphylactic reactions should avoid them. 1, 2
Avoid these antibiotics for streptococcal pharyngitis:
- Tetracyclines - high prevalence of resistant strains 3
- Sulfonamides and trimethoprim-sulfamethoxazole - do not eradicate Group A Streptococcus 3
- Older fluoroquinolones (ciprofloxacin) - limited activity against Group A Streptococcus 3
- Newer fluoroquinolones (levofloxacin, moxifloxacin) - unnecessarily broad spectrum and expensive 3
Special Populations and Considerations
Chronic carriers generally do not require antimicrobial therapy, as they are unlikely to spread infection or develop complications. 1, 2
- If treatment is indicated for chronic carriers, clindamycin is particularly effective due to its ability to eradicate the organism 1, 4
Routine post-treatment cultures are not recommended for asymptomatic patients who have completed therapy, except in special circumstances such as patients with a history of rheumatic fever. 1, 2
Adjunctive Therapy
Consider acetaminophen or NSAIDs for moderate to severe symptoms or high fever as adjuncts to appropriate antibiotic therapy. 3, 1