What is a suitable antibiotic regimen for a patient with a penicillin (PCN) allergy diagnosed with strep throat?

Antibiotic Regimen for Strep Throat in Penicillin-Allergic Patients

For patients with non-immediate (non-anaphylactic) penicillin allergy, prescribe a first-generation cephalosporin such as cephalexin 500 mg orally twice daily for 10 days; for patients with immediate/anaphylactic penicillin allergy, prescribe clindamycin 300 mg orally three times daily for 10 days. 1, 2

Treatment Algorithm Based on Type of Penicillin Allergy

The critical first step is determining whether the patient experienced an immediate/anaphylactic reaction (anaphylaxis, angioedema, respiratory distress, or urticaria within 1 hour of penicillin administration) versus a non-immediate reaction (delayed rash, mild gastrointestinal symptoms). 1, 3

For Non-Immediate Penicillin Allergy

• First-generation cephalosporins are the preferred first-line alternatives with strong, high-quality evidence supporting their efficacy. 4, 1
• Cephalexin 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days is recommended. 1
• Cefadroxil 30 mg/kg once daily (maximum 1 gram) for 10 days is an acceptable alternative. 1
• The cross-reactivity risk with first-generation cephalosporins is only 0.1% in patients with non-severe, delayed penicillin reactions. 1
• These narrow-spectrum agents are preferred over broad-spectrum cephalosporins due to lower cost, proven efficacy, and reduced selection pressure for antibiotic-resistant flora. 4

For Immediate/Anaphylactic Penicillin Allergy

• All beta-lactam antibiotics, including cephalosporins, must be avoided due to up to 10% cross-reactivity risk. 4, 1, 2
• Clindamycin is the preferred choice with strong, moderate-quality evidence: 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days. 1, 2
• Clindamycin demonstrates high efficacy in eradicating Group A Streptococcus, even in chronic carriers, with only approximately 1% resistance among isolates in the United States. 4, 1, 2

Alternative Options for Immediate Allergy

• Azithromycin 12 mg/kg once daily (maximum 500 mg) for 5 days is acceptable but less preferred due to 5-8% macrolide resistance rates in the United States. 1, 2
• Azithromycin is the only antibiotic requiring just 5 days due to its prolonged tissue half-life. 1, 2
• Clarithromycin 7.5 mg/kg per dose twice daily (maximum 250 mg per dose) for 10 days is another option but shares the same resistance concerns as azithromycin. 1
• Erythromycin 20-40 mg/kg/day divided 2-3 times daily (maximum 1 gram per day) for 10 days is the least preferred macrolide due to substantially higher rates of gastrointestinal side effects. 4, 5

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. 4, 1, 2
• Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk. 1
• The American Heart Association recommends 10 days of therapy for streptococcal pharyngitis to prevent rheumatic fever. 5

Important Resistance Considerations

• Macrolide resistance among Group A Streptococcus varies geographically and temporally, with approximately 5-8% resistance in the United States, though some areas experience much higher rates. 4, 1, 2
• Clindamycin resistance remains very low at approximately 1% in the United States, making it more reliable than macrolides when beta-lactams cannot be used. 4, 1, 2
• Be aware of local resistance patterns before prescribing macrolides, as resistance can exceed 10% in some regions. 1

Common Pitfalls to Avoid

• Do not assume all penicillin-allergic patients cannot receive cephalosporins - only those with immediate/anaphylactic reactions should avoid them. 1
• Do not prescribe broad-spectrum cephalosporins (cefaclor, cefuroxime, cefixime, cefdinir, cefpodoxime) when narrow-spectrum first-generation agents are appropriate, as they are more expensive and more likely to select for antibiotic-resistant flora. 4
• 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, 2
• Do not use trimethoprim-sulfamethoxazole (Bactrim) for strep throat due to high resistance rates and lack of efficacy against Group A Streptococcus. 1

Adjunctive Therapy

• Acetaminophen or NSAIDs (such as ibuprofen) should be considered for moderate to severe symptoms or high fever. 1, 2
• Aspirin must be avoided in children due to the risk of Reye syndrome. 1, 2
• Corticosteroids are not recommended as adjunctive therapy. 1, 2