What antibiotics are recommended for a patient with a known amoxicillin (amoxicillin) allergy and streptococcal pharyngitis (strep throat)?

Antibiotics for Strep Throat in Amoxicillin-Allergic Patients

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

Critical First Step: Determine the Type of Allergy

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

• Non-immediate reactions (delayed rash, mild symptoms occurring >1 hour after administration) carry only 0.1% cross-reactivity risk with cephalosporins 1
• Immediate/anaphylactic reactions (anaphylaxis, angioedema, respiratory distress, urticaria within 1 hour) carry up to 10% cross-reactivity risk with all beta-lactam antibiotics including cephalosporins 1, 2

Treatment Algorithm

For Non-Immediate Amoxicillin Allergy

First-line: Cephalexin 1, 3

• Dosing: 500 mg orally twice daily for 10 days (adults); 20 mg/kg per dose twice daily for children (max 500 mg/dose) 1
• Alternative: Cefadroxil 1 gram once daily for 10 days (adults); 30 mg/kg once daily for children (max 1 gram) 1
• Evidence: Strong, high-quality evidence supports first-generation cephalosporins as preferred alternatives with proven efficacy, narrow spectrum, and low cost 1, 3

For Immediate/Anaphylactic Amoxicillin Allergy

All cephalosporins must be avoided due to 10% cross-reactivity risk 1, 2

First-line: Clindamycin 1, 3

• Dosing: 300 mg orally three times daily for 10 days (adults); 7 mg/kg per dose three times daily for children (max 300 mg/dose) 1
• Evidence: Strong, moderate-quality evidence with only ~1% resistance rate among Group A Streptococcus in the United States 1, 3
• Advantages: Highly effective even in chronic carriers who have failed penicillin treatment 1

Second-line: Azithromycin 1, 3, 4

• Dosing: 500 mg once daily for 5 days (adults); 12 mg/kg once daily for children (max 500 mg) 1, 4
• Evidence: Acceptable alternative but has 5-8% macrolide resistance in the United States 1, 3
• Unique feature: Only antibiotic requiring just 5 days due to prolonged tissue half-life 1, 3
• FDA indication: Approved for pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy 4

Third-line: Clarithromycin 1

• Dosing: 250 mg orally twice daily for 10 days (adults); 7.5 mg/kg per dose twice daily for children (max 250 mg/dose) 1
• Same resistance concerns as azithromycin (5-8% macrolide resistance) 1

Critical 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 and rheumatic fever risk 1, 3.

Azithromycin is the only exception, requiring just 5 days due to its unique pharmacokinetics and prolonged tissue half-life 1, 3, 4.

Common Pitfalls to Avoid

• Never use cephalosporins in patients with immediate/anaphylactic amoxicillin reactions - the 10% cross-reactivity risk makes this dangerous 1, 2, 3
• Do not assume all amoxicillin-allergic patients cannot receive cephalosporins - only those with immediate/anaphylactic reactions should avoid them 1
• Do not shorten antibiotic courses below 10 days (except azithromycin's 5-day regimen) as this dramatically increases treatment failure and rheumatic fever risk 1, 3
• Check local macrolide resistance patterns before prescribing azithromycin or clarithromycin - resistance varies geographically and can exceed 5-8% in some areas 1, 3
• Do not use trimethoprim-sulfamethoxazole (Bactrim) - it has 50% resistance rates and is not recommended for Group A Streptococcus 1

Why Clindamycin Over Macrolides for Immediate Allergy

Clindamycin is preferred over azithromycin/clarithromycin for immediate penicillin allergy because 1, 3:

• Only ~1% resistance rate versus 5-8% for macrolides
• More reliable eradication even in chronic carriers
• No geographic variability in resistance patterns

However, azithromycin remains acceptable when compliance with a 10-day regimen is unlikely, as its 5-day course improves adherence 1.

Post-Treatment Considerations

Routine follow-up throat cultures are not recommended for asymptomatic patients who have completed therapy 1, 3. Testing should only be considered in special circumstances such as patients with a history of rheumatic fever 1, 3.

Adjunctive Therapy

• Use acetaminophen or NSAIDs (like 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