What is the recommended treatment for a patient with a Penicillin (PCN) allergy diagnosed with strep throat?

Treatment of Strep Throat with Penicillin Allergy

For patients with non-immediate (non-anaphylactic) penicillin allergy, first-generation cephalosporins such as cephalexin 500 mg twice daily for 10 days are the preferred first-line treatment, with strong high-quality evidence and only 0.1% cross-reactivity risk. 1

Determine the Type of Penicillin Allergy First

The critical first step is distinguishing between immediate/anaphylactic versus non-immediate reactions, as this fundamentally changes which antibiotics are safe 1:

• Immediate/anaphylactic reactions include anaphylaxis, angioedema, respiratory distress, or urticaria occurring within 1 hour of penicillin administration 1
• Non-immediate reactions include delayed rashes, mild gastrointestinal symptoms, or other non-life-threatening reactions occurring after 1 hour 1

Treatment Algorithm Based on Allergy Type

For Non-Immediate Penicillin Allergy (Preferred Approach)

First-generation cephalosporins are the treatment of choice 1, 2:

• Cephalexin: 500 mg orally twice daily for 10 days (adults) or 20 mg/kg per dose twice daily for 10 days (children, maximum 500 mg/dose) 1
• Cefadroxil: 30 mg/kg once daily for 10 days (alternative option) 1
• Cross-reactivity risk is only 0.1% in patients with non-severe, delayed penicillin reactions 1
• Strong, high-quality evidence supports efficacy comparable to penicillin 1

For Immediate/Anaphylactic Penicillin Allergy

All beta-lactam antibiotics must be avoided due to up to 10% cross-reactivity risk 1, 2. Use these alternatives:

Clindamycin (Preferred) 1:

• Adults: 300 mg orally three times daily for 10 days
• Children: 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days
• Only ~1% resistance rate among Group A Streptococcus in the United States 1
• Strong, moderate-quality evidence with high efficacy even in chronic carriers 1
• Particularly effective for treatment failures or recurrent infections 1

Azithromycin (Alternative) 1, 3:

• Adults: 500 mg once daily for 5 days (or 12 mg/kg once daily, maximum 500 mg)
• Children: 12 mg/kg once daily (maximum 500 mg) for 5 days
• Only antibiotic requiring just 5 days due to prolonged tissue half-life 1
• However, 5-8% macrolide resistance in the United States (varies geographically) 1
• Should be reserved for patients who cannot tolerate clindamycin or cephalosporins 1

Clarithromycin (Alternative) 1, 3:

• Adults: 250 mg orally twice daily for 10 days
• Children: 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days
• Same resistance concerns as azithromycin (5-8% macrolide resistance) 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, 4. Shortening the course by even a few days dramatically increases treatment failure rates and rheumatic fever risk 1.

Important Resistance Considerations

• Clindamycin resistance: Only ~1% in the United States, making it highly reliable 1
• Macrolide resistance: 5-8% nationally but varies geographically—some areas have much higher rates 1
• Penicillin resistance: No documented resistance anywhere in the world 1
• Be aware of local resistance patterns when prescribing macrolides 1, 2

Common Pitfalls to Avoid

• Do not assume all penicillin-allergic patients need to avoid cephalosporins—only those with immediate/anaphylactic reactions should avoid them 1
• Do not use cephalosporins in patients with immediate hypersensitivity due to 10% cross-reactivity risk 1, 2
• Do not prescribe broad-spectrum cephalosporins (cefdinir, cefpodoxime, cefixime) when narrow-spectrum first-generation agents are appropriate—they are more expensive and select for resistant flora 1
• Do not shorten antibiotic courses below 10 days (except azithromycin's 5-day regimen)—this increases treatment failure and rheumatic fever risk 1, 4
• Do not use azithromycin as first-line therapy—it should be reserved for true penicillin allergy due to resistance concerns 1
• Do not use trimethoprim-sulfamethoxazole (Bactrim) for strep throat—it has high resistance rates and is not recommended 1

Adjunctive Therapy

• Acetaminophen or NSAIDs (such as ibuprofen) for moderate to severe symptoms or high fever 1
• Avoid aspirin in children due to Reye syndrome risk 1
• Do not use corticosteroids as adjunctive therapy 1

Special Considerations for Treatment Failures or Chronic Carriers

If a patient has failed initial antibiotic therapy or has recurrent infections 1:

• Clindamycin demonstrates superior eradication rates in chronic carriers and treatment failures 1
• Consider whether the patient is a chronic carrier experiencing viral pharyngitis rather than true recurrent streptococcal infections 1
• Chronic carriers generally do not require treatment unless special circumstances exist (community outbreak, family history of rheumatic fever) 1