What are alternative antibiotics for a patient with a penicillin (PCN) allergy who has anaphylactic reactions and is diagnosed with streptococcal pharyngitis (strep throat)?

Treatment of Streptococcal Pharyngitis in Patients with Anaphylactic Penicillin Allergy

For patients with anaphylactic penicillin allergy and strep throat, use clindamycin 7 mg/kg three times daily (maximum 300 mg/dose) for 10 days as the preferred first-line alternative, or azithromycin 12 mg/kg once daily (maximum 500 mg) for 5 days as an acceptable alternative. 1

Treatment Algorithm for Anaphylactic Penicillin Allergy

Avoid All Beta-Lactams

• Patients with immediate/anaphylactic penicillin reactions must avoid all cephalosporins due to up to 10% cross-reactivity risk with first-generation cephalosporins 2, 1
• This includes cephalexin and cefadroxil, which are only safe for non-anaphylactic penicillin allergies 1

First-Line: Clindamycin

• Clindamycin is the preferred alternative for anaphylactic penicillin allergy with strong, moderate-quality evidence supporting its efficacy 1
• Dosing: 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days 2, 1
• Clindamycin demonstrates high efficacy in eradicating streptococci, even in chronic carriers 1
• Clindamycin resistance among Group A Streptococcus isolates in the United States is approximately 1%, making it highly reliable 1

Acceptable Alternative: Azithromycin

• Azithromycin 12 mg/kg once daily (maximum 500 mg) for 5 days is an acceptable alternative 2, 1
• Azithromycin requires only 5 days of treatment due to its prolonged tissue half-life, unlike other antibiotics that require 10 days 2, 1
• In clinical trials, azithromycin achieved 95% bacteriologic eradication at Day 14 and 77% at Day 30 when compared to penicillin V 3
• The FDA label confirms azithromycin is indicated for pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy 3

Other Macrolide Option: Clarithromycin

• Clarithromycin 7.5 mg/kg twice daily (maximum 250 mg/dose) for 10 days is also acceptable 2, 1
• Clarithromycin has strong, moderate-quality evidence but requires the full 10-day course 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
• Azithromycin is the only exception, requiring only 5 days due to its unique pharmacokinetics 2, 1
• Prescribing shorter courses than recommended (except for azithromycin) can lead to treatment failure and complications 1

Important Resistance Considerations

Macrolide Resistance

• Macrolide resistance among Group A Streptococcus varies geographically and temporally, with approximately 5-8% resistance in the United States 1
• Be aware of local macrolide resistance patterns before prescribing azithromycin or clarithromycin 1, 4
• In areas with high macrolide resistance, clindamycin becomes even more important as the preferred alternative 1

Clindamycin Advantage

• Clindamycin resistance is only approximately 1% in the United States, making it more reliable than macrolides in areas with resistance concerns 1

Common Pitfalls to Avoid

• Never use first-generation cephalosporins in patients with immediate/anaphylactic penicillin reactions due to the 10% cross-reactivity risk 1, 4
• Do not assume all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them 1
• Avoid trimethoprim-sulfamethoxazole (Bactrim) for strep throat due to high resistance rates (50%) and lack of efficacy against Group A Streptococcus 1
• Do not prescribe inadequate treatment durations, as this can lead to complications such as rheumatic fever 5

Adjunctive Therapy

• Use acetaminophen or NSAIDs for moderate to severe symptoms or high fever 2, 1
• Avoid aspirin in children due to risk of Reye syndrome 2, 1
• Corticosteroids are not recommended as adjunctive therapy 2, 1

Special Considerations

• For patients with recurrent streptococcal pharyngitis, clindamycin may be particularly effective due to its ability to eradicate the organism in chronic carriers 1, 4
• Routine post-treatment throat cultures are not recommended for asymptomatic patients who have completed therapy 5