Antibiotic Treatment for Strep Throat with Penicillin Allergy
For patients with non-immediate penicillin allergy, first-generation cephalosporins (cephalexin 500 mg twice daily or cefadroxil 1 gram once daily for 10 days) are the preferred first-line alternatives; for patients with immediate/anaphylactic penicillin allergy, clindamycin 300 mg three times daily for 10 days is the treatment of choice. 1, 2
Treatment Algorithm Based on Type of Penicillin Allergy
Non-Immediate Penicillin Allergy (No History of Anaphylaxis, Angioedema, or Urticaria)
- First-generation cephalosporins are the preferred option with strong, high-quality evidence supporting their efficacy and cost-effectiveness 1, 2
- Cephalexin: 500 mg twice daily for 10 days 2
- Cefadroxil: 1 gram once daily for 10 days 2
- These agents have demonstrated superior bacteriologic eradication rates compared to penicillin in multiple studies 1
Immediate/Anaphylactic Penicillin Allergy
Clindamycin is the preferred choice with strong, moderate-quality evidence and approximately 1% resistance rate among Group A Streptococcus in the United States 1, 3
Dosing: 300 mg three times daily for 10 days 1
Clindamycin demonstrates high efficacy in eradicating streptococci, even in chronic carriers 1
Azithromycin is an acceptable alternative when clindamycin cannot be used 1, 4
Dosing: 500 mg on day 1, then 250 mg once daily for days 2-5 (total 5-day course) 1
The FDA label confirms azithromycin is indicated as an alternative to first-line therapy in individuals who cannot use first-line therapy 4
Azithromycin requires only 5 days due to its prolonged tissue half-life 1
Critical Safety Consideration
Up to 10% of patients with immediate hypersensitivity to penicillin may have cross-reactivity with first-generation cephalosporins, so cephalosporins must be avoided in patients with anaphylactic-type reactions to penicillin. 1, 2, 3
Treatment Duration Requirements
- All antibiotics except azithromycin require a full 10-day course to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever 1, 2, 3
- Shortening the course by even a few days results in appreciable increases in treatment failure rates 1
- Azithromycin is the only exception, requiring 5 days due to its unique pharmacokinetics 1, 4
Resistance Considerations
- Macrolide resistance among Group A Streptococcus is approximately 5-8% in the United States, though this varies geographically 1, 3
- The FDA label warns that susceptibility tests should be performed when treating with azithromycin because some strains are resistant 4
- Clindamycin resistance remains very low at approximately 1% in the United States 1, 3
- Be aware of local resistance patterns before prescribing macrolides 1
Efficacy Evidence
- In FDA-approved studies, azithromycin (12 mg/kg once daily for 5 days in pediatrics) was clinically and microbiologically superior to penicillin V at Day 14 and Day 30, with bacteriologic eradication rates of 95% vs 73% at Day 14 4
- First-generation cephalosporins have strong, high-quality evidence for efficacy in non-anaphylactic penicillin-allergic patients 1, 2, 3
Common Pitfalls to Avoid
- Do not prescribe cephalosporins to patients with immediate/anaphylactic penicillin reactions due to the 10% cross-reactivity risk 1, 2
- Do not prescribe shorter courses than recommended (except azithromycin's 5-day regimen) to prevent treatment failure and 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
- Do not use azithromycin as first-line therapy - it should only be used when penicillin and preferred alternatives cannot be used 1
Adjunctive Therapy
- Acetaminophen or NSAIDs (such as ibuprofen) should be considered for moderate to severe symptoms or high fever 1, 3
- Aspirin must be avoided in children due to the risk of Reye syndrome 1, 3
- Corticosteroids are not recommended as adjunctive therapy 1