What is the appropriate first‑line antibiotic for a patient with confirmed group A streptococcal infection who is allergic to penicillin and azithromycin?

Recommended Antibiotic for Penicillin- and Azithromycin-Allergic Patients with Strep Throat

For a patient with confirmed Group A streptococcal pharyngitis who is allergic to both penicillin and azithromycin, prescribe oral clindamycin 300 mg three times daily for a full 10-day course.

Critical Allergy Assessment First

• The type of penicillin allergy determines whether first-generation cephalosporins can be safely used—patients with immediate/anaphylactic reactions (anaphylaxis, angioedema, urticaria within 1 hour) must avoid all beta-lactams due to up to 10% cross-reactivity risk. 1, 2
• Patients with non-immediate (delayed) penicillin reactions have only 0.1% cross-reactivity with first-generation cephalosporins, making cephalexin or cefadroxil safe alternatives. 1, 2
• Since the question specifies azithromycin allergy, macrolides (azithromycin, clarithromycin, erythromycin) should be avoided entirely. 1

Why Clindamycin Is the Optimal Choice

• Clindamycin is the preferred alternative for patients with immediate/anaphylactic penicillin allergy who cannot use macrolides, with strong, moderate-quality evidence supporting its efficacy. 1, 2, 3
• Clindamycin resistance among Group A Streptococcus in the United States is only approximately 1%, making it highly reliable. 1, 2
• The FDA specifically indicates clindamycin for serious streptococcal infections in penicillin-allergic patients. 3
• Clindamycin demonstrates substantially higher eradication rates than penicillin in chronic carriers and treatment failures. 1

Specific Dosing Regimen

• Adults: Clindamycin 300 mg orally three times daily for 10 days. 1, 3
• Pediatric patients: Clindamycin 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days. 1, 2

Critical Treatment Duration Requirement

• A full 10-day course is mandatory to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever. 1, 2
• Shortening the course by even a few days leads to appreciable increases in treatment failure rates and rheumatic fever risk. 1
• Even if symptoms resolve within 3–4 days, the full 10-day course must be completed. 1

Alternative Option If Non-Immediate Penicillin Allergy

• If the penicillin allergy is non-immediate (delayed rash occurring >1 hour after exposure), first-generation cephalosporins are preferred over clindamycin due to stronger evidence and lower cost. 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 per dose). 1, 2
• Cefadroxil 1 gram orally once daily for 10 days (adults) or 30 mg/kg once daily for 10 days (children). 1, 2

Common Pitfalls to Avoid

• Do not prescribe cephalosporins if the patient had anaphylaxis, angioedema, or immediate urticaria to penicillin—the 10% cross-reactivity risk makes all beta-lactams unsafe. 1, 2
• Do not prescribe trimethoprim-sulfamethoxazole (Bactrim)—it fails to eradicate Group A Streptococcus in 20–25% of cases and is absolutely contraindicated. 1
• Do not shorten the clindamycin course below 10 days, as this dramatically increases treatment failure and rheumatic fever risk. 1, 2
• Do not order routine post-treatment throat cultures for asymptomatic patients who have completed therapy. 1

Adjunctive Symptomatic Treatment

• Offer acetaminophen or NSAIDs (ibuprofen) for moderate to severe sore throat or high fever. 1, 2
• Avoid aspirin in children due to Reye syndrome risk. 1, 2
• Corticosteroids are not recommended as adjunctive therapy. 1

Patient Counseling

• Emphasize completing the entire 10-day clindamycin regimen even if symptoms improve rapidly, to prevent acute rheumatic fever and reduce treatment failure. 1
• Warn about potential gastrointestinal side effects with clindamycin, including the rare but serious risk of Clostridioides difficile colitis. 3