What is the recommended antibiotic treatment for strep throat in patients with a penicillin allergy?

Antibiotic Treatment for Strep Throat in Patients with Penicillin Allergy

For patients with penicillin allergy, the recommended first-line antibiotic treatment for strep throat is cephalexin (for non-anaphylactic penicillin allergy) or clarithromycin/azithromycin (for severe/anaphylactic penicillin allergy). 1

Treatment Algorithm Based on Type of Penicillin Allergy

Non-Anaphylactic Penicillin Allergy

• First-generation cephalosporins are recommended as first-line alternatives 1
  • Cephalexin: 20 mg/kg per dose twice daily for 10 days (maximum 500 mg per dose) 1
  • Cefadroxil: 30 mg/kg once daily for 10 days (maximum 1 g per day) 1
• Up to 10% of patients with immediate hypersensitivity to penicillin may have cross-reactivity with first-generation cephalosporins, so these should be avoided in patients with history of anaphylaxis 1

Severe/Anaphylactic Penicillin Allergy

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

Efficacy and Evidence Quality

• First-generation cephalosporins have strong evidence for efficacy in non-anaphylactic penicillin-allergic patients 1
• Clindamycin demonstrates high efficacy in eradicating streptococci, even in chronic carriers 1
• Macrolides (clarithromycin, azithromycin) have moderate-quality evidence but carry concerns about resistance 1
• In clinical trials, azithromycin was statistically superior to penicillin in clinical success rates for streptococcal pharyngitis at both day 14 (98% vs 84%) and day 30 (94% vs 74%) 2

Duration of Therapy

• Most antibiotics require a full 10-day course to achieve maximal pharyngeal eradication of Group A Streptococcus 1
• Azithromycin is the exception, requiring only a 5-day course due to its prolonged tissue half-life 1, 2

Important Considerations and Potential Pitfalls

• Macrolide resistance among Group A Streptococcus varies geographically, with approximately 5-8% resistance in the United States 1, 3
• Clindamycin resistance among Group A Streptococcus isolates in the United States is approximately 1% 1
• Prescribing shorter courses than recommended (except for azithromycin) can lead to treatment failure and complications 1
• A common mistake is assuming all penicillin-allergic patients cannot receive cephalosporins - only those with immediate/anaphylactic reactions should avoid them 1
• Azithromycin is generally well-tolerated in patients with penicillin allergies 4

Side Effects and Tolerability

• The most common side effects of azithromycin are gastrointestinal: diarrhea/loose stools (6%), vomiting (6%), and abdominal pain (3%) 2
• Macrolides (especially erythromycin and clarithromycin) can cause prolongation of the QT interval in a dose-dependent manner 5
• Newer macrolides (clarithromycin and azithromycin) offer lower rates of gastrointestinal complaints compared to erythromycin 6

Special Populations and Situations

• For patients with recurrent streptococcal pharyngitis, clindamycin may be particularly effective due to its ability to eradicate the organism in chronic carriers 1
• In areas with high macrolide resistance, cephalexin is the preferred option for patients with severe penicillin allergy 3
• Penicillin remains the drug of choice for non-allergic patients due to its narrow spectrum, effectiveness, and low cost 7, 8