What is the recommended treatment for an immunocompetent adult patient with strep throat and a known allergy to amoxicillin (a type of penicillin)?

Treatment for Strep Throat with Amoxicillin Allergy

For an immunocompetent adult with strep throat and amoxicillin allergy, use cephalexin 500 mg orally twice daily for 10 days if the allergy was non-immediate (e.g., delayed rash), or clindamycin 300 mg orally three times daily for 10 days if the allergy was immediate/anaphylactic (e.g., hives, angioedema, or anaphylaxis within 1 hour). 1, 2

Critical First Step: Determine the Type of Allergic Reaction

The type of penicillin allergy fundamentally changes which antibiotics are safe:

• Non-immediate/delayed reactions (e.g., rash appearing days later, mild skin reactions) carry only 0.1% cross-reactivity risk with cephalosporins, making first-generation cephalosporins safe and preferred 1, 2

• Immediate/anaphylactic reactions (e.g., anaphylaxis, angioedema, urticaria, or respiratory distress within 1 hour of penicillin) carry up to 10% cross-reactivity risk with cephalosporins, requiring complete avoidance of all beta-lactam antibiotics 1, 2

Treatment Algorithm Based on Allergy Type

For Non-Immediate Amoxicillin Allergy (Preferred Approach)

First-generation cephalosporins are the treatment of choice with strong, high-quality evidence: 1, 2

• Cephalexin 500 mg orally twice daily for 10 days (preferred due to twice-daily dosing) 1, 2
• Cefadroxil 1 gram orally once daily for 10 days (alternative with once-daily convenience) 1, 2

These agents have narrow spectrum activity, proven efficacy comparable to penicillin, essentially zero resistance among Group A Streptococcus, and low cost 1, 2

For Immediate/Anaphylactic Amoxicillin Allergy

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

• Clindamycin 300 mg orally three times daily for 10 days 1, 2
• Clindamycin has only ~1% resistance among Group A Streptococcus in the United States 1, 3
• Particularly effective in chronic carriers and treatment failures 1

Azithromycin is an acceptable alternative if clindamycin cannot be used: 2, 3

• Azithromycin 500 mg orally once daily for 5 days 2, 3
• Only requires 5 days due to prolonged tissue half-life 1, 3
• However, macrolide resistance is 5-8% in the United States and varies geographically 1, 3
• Clindamycin is more reliable due to lower resistance rates 1, 2

Critical Treatment Duration Requirements

A full 10-day course is essential for all antibiotics except azithromycin (which requires 5 days) to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever. 1, 2 Shortening the course by even a few days dramatically increases treatment failure rates and rheumatic fever risk 1, 2

Common Pitfalls to Avoid

• Do not use cephalosporins if the patient had anaphylaxis, angioedema, or immediate urticaria to amoxicillin - the 10% cross-reactivity risk makes this dangerous 1, 2

• Do not assume all penicillin-allergic patients need to avoid cephalosporins - only those with immediate/anaphylactic reactions should avoid them 1, 2

• Do not prescribe azithromycin as first-line therapy - it should be reserved for patients who cannot use cephalosporins or clindamycin due to resistance concerns 3

• Do not shorten the antibiotic course below 10 days (except azithromycin's 5-day regimen) as this increases treatment failure and rheumatic fever 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

Adjunctive Symptomatic Treatment

• Acetaminophen or NSAIDs (ibuprofen) for moderate to severe symptoms or high fever 1, 3
• Avoid aspirin in children due to Reye syndrome risk 1, 3
• Do not use corticosteroids as adjunctive therapy 1, 3

Why This Hierarchy Matters

First-generation cephalosporins have the strongest evidence (strong, high-quality) for non-immediate allergy, while clindamycin has strong, moderate-quality evidence for immediate allergy 1, 2. Azithromycin also has strong, moderate-quality evidence but carries higher resistance concerns 1, 3. The primary goal is not just symptom relief but prevention of acute rheumatic fever and suppurative complications, which requires complete bacterial eradication 1.