What is a suitable antibiotic for a patient with strep throat who is allergic to penicillin (PCN)?

Treatment of Strep Throat in Penicillin-Allergic Patients

For patients with non-immediate (non-anaphylactic) penicillin allergy, use first-generation cephalosporins like cephalexin 500 mg twice daily for 10 days; for patients with immediate/anaphylactic penicillin reactions, use clindamycin 300 mg three times daily for 10 days as the preferred alternative. 1

Critical First Step: Determine the Type of Penicillin Allergy

The type of penicillin reaction dictates which antibiotics are safe versus dangerous:

• Immediate/anaphylactic reactions include anaphylaxis, angioedema, respiratory distress, or urticaria occurring within 1 hour of penicillin administration 1
• Non-immediate reactions are delayed reactions without the above features 1
• This distinction is critical because patients with immediate hypersensitivity have up to 10% cross-reactivity with cephalosporins and must avoid all beta-lactam antibiotics 1, 2
• Patients with non-immediate reactions have only 0.1% cross-reactivity risk with cephalosporins, making them safe to use 3

Treatment Algorithm Based on Allergy Type

For Non-Immediate Penicillin Allergy (Preferred Option)

First-generation cephalosporins are the preferred first-line alternatives with strong, high-quality evidence supporting their efficacy 1:

• Adults: Cephalexin 500 mg orally every 12 hours for 10 days 1
• Children: Cephalexin 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days 1
• Alternative: Cefadroxil 30 mg/kg once daily (maximum 1 gram) for 10 days 1

These agents offer narrow spectrum, proven effectiveness, and low cost compared to other alternatives 1, 3

For Immediate/Anaphylactic Penicillin Allergy

Clindamycin is the preferred choice with strong, moderate-quality evidence 1, 2:

• Adults: Clindamycin 300 mg orally three times daily for 10 days 1, 2
• Children: Clindamycin 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days 1, 2

Why clindamycin is preferred:

• Demonstrates high efficacy in eradicating streptococci, even in chronic carriers 1, 2
• Only approximately 1% resistance among Group A Streptococcus in the United States 1, 2
• More reliable than macrolides in areas with resistance concerns 2

Alternative: Macrolides (Less Preferred)

If clindamycin cannot be used, macrolides are acceptable alternatives 1:

• Azithromycin: 500 mg once daily for 5 days (adults) or 12 mg/kg once daily (maximum 500 mg) for 5 days (children) 1, 2, 4
• Clarithromycin: 250 mg twice daily for 10 days (adults) or 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days (children) 1

Important caveats about macrolides:

• Macrolide resistance is 5-8% in the United States and varies geographically 1, 2
• Azithromycin is FDA-approved for strep throat "as an alternative to first-line therapy in individuals who cannot use first-line therapy" 4
• A 2001 study showed 10 days of clarithromycin was more effective than 5 days of azithromycin in eradicating Group A Streptococcus (91% vs 82%, P=0.012) 5

Critical Treatment Duration Requirements

A full 10-day course is mandatory for all antibiotics except azithromycin to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever 1, 3, 2:

• Azithromycin is the only exception, requiring only 5 days due to its prolonged tissue half-life 1, 2, 4
• Shortening the course by even a few days results in appreciable increases in treatment failure rates 1
• The primary goal is not just symptomatic improvement but prevention of acute rheumatic fever, which requires adequate bacterial eradication 1

Common Pitfalls to Avoid

• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to 10% cross-reactivity risk 1, 2
• Do not assume all penicillin-allergic patients cannot receive cephalosporins - only those with immediate reactions should avoid them 1
• Do not prescribe shorter courses than recommended (except azithromycin's 5-day regimen) as this increases treatment failure and rheumatic fever risk 1, 3
• Do not use trimethoprim-sulfamethoxazole (Bactrim) for strep throat due to high resistance rates and lack of efficacy against Group A Streptococcus 1
• Be aware of local macrolide resistance patterns before prescribing azithromycin or clarithromycin, as resistance can be much higher than 5-8% in some areas 1

Adjunctive Therapy

• For symptom relief: Acetaminophen or NSAIDs (ibuprofen) for moderate to severe symptoms or high fever 1, 2
• Avoid aspirin in children due to risk of Reye syndrome 1, 2
• Do not use corticosteroids as adjunctive therapy 1, 2