What is the recommended treatment for an adult with a Penicillin (PCN) allergy diagnosed with streptococcal pharyngitis (strep throat)?

Treatment for Strep Throat in Adults with Penicillin Allergy

For adults with penicillin allergy and strep throat, use first-generation cephalosporins (cephalexin 500 mg twice daily for 10 days) if the allergy is non-immediate/non-anaphylactic, or clindamycin (300 mg three times daily for 10 days) if the allergy is immediate/anaphylactic. 1, 2

Determine the Type of Penicillin Allergy First

The critical first step is distinguishing between immediate and non-immediate reactions, as this determines whether cephalosporins can be safely used 1:

• Immediate/anaphylactic reactions include anaphylaxis, angioedema, respiratory distress, or urticaria occurring within 1 hour of penicillin administration 1
• Non-immediate reactions are delayed, non-severe reactions such as rash appearing hours to days later 1

Treatment Algorithm Based on Allergy Type

For Non-Immediate Penicillin Allergy (Preferred Option)

First-generation cephalosporins are the preferred first-line alternative with strong, high-quality evidence supporting their efficacy 1, 2:

• Cephalexin 500 mg orally twice daily for 10 days 1, 2
• Cefadroxil 1 gram orally once daily for 10 days 1, 2
• Cross-reactivity risk is only 0.1% in patients with non-severe, delayed penicillin reactions 1
• These agents have narrow spectrum, proven efficacy, and low cost 1

For Immediate/Anaphylactic Penicillin Allergy

Avoid all beta-lactams including cephalosporins due to up to 10% cross-reactivity risk 1, 2, 3

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

• Clindamycin 300 mg orally three times daily for 10 days 1, 2
• Approximately 1% resistance rate among Group A Streptococcus in the United States 1
• Highly effective in eradicating streptococci, even in chronic carriers 1

Azithromycin is an acceptable alternative 1, 2:

• Azithromycin 500 mg orally once daily for 5 days 1, 4
• Only requires 5 days due to prolonged tissue half-life 1, 4
• Macrolide resistance is 5-8% in the United States, varying geographically 1, 5
• Clinical cure rates of 94-98% at 30 days in comparative trials 4, 6

Clarithromycin is also an option 1:

• Clarithromycin 250 mg orally twice daily for 10 days 1
• Similar resistance concerns as azithromycin 1

Critical Treatment Duration Requirements

A full 10-day course is essential for all antibiotics except azithromycin 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, 2
• Azithromycin is the only exception, requiring only 5 days due to its unique pharmacokinetics 1, 4
• The primary goal is not just symptomatic improvement but prevention of acute rheumatic fever, which requires adequate bacterial eradication 1

Evidence Quality and Relative Strengths

The evidence hierarchy for penicillin alternatives 2:

• First-generation cephalosporins for non-immediate allergy: Strong, high-quality evidence from multiple guidelines 1, 2
• Clindamycin: Strong, moderate-quality evidence, particularly effective in treatment failures and carriers 1, 2
• Macrolides (azithromycin/clarithromycin): Strong, moderate-quality evidence but with resistance concerns 1, 2, 5

Common Pitfalls to Avoid

• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to the 10% cross-reactivity risk 1, 2, 3
• Do not assume all penicillin-allergic patients cannot receive cephalosporins - only those with immediate/anaphylactic reactions should avoid them 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 use azithromycin as first-line therapy - it should only be used when penicillin and preferred alternatives cannot be used 1
• Be aware of local macrolide resistance patterns before prescribing azithromycin or clarithromycin, as resistance varies geographically and can lead to treatment failure 1, 5

Adjunctive Therapy

• Acetaminophen or NSAIDs (such as ibuprofen) should be considered for moderate to severe symptoms or high fever 1
• Avoid aspirin in children due to Reye syndrome risk 1
• Corticosteroids are not recommended as adjunctive therapy 1

Post-Treatment Considerations

• Routine follow-up throat cultures are not recommended for asymptomatic patients who have completed therapy 1, 2
• Consider follow-up testing only in special circumstances, such as patients with a history of rheumatic fever 1
• Patients with worsening symptoms after appropriate antibiotic initiation or with symptoms lasting 5 days after the start of treatment should be reevaluated 5