What is a suitable treatment for an adult or child with strep (Group A beta-hemolytic streptococcal) pharyngitis who is allergic to penicillin and azithromycin (Zithromax)?

Treatment of Strep Pharyngitis with Penicillin and Azithromycin Allergy

For patients allergic to both penicillin and azithromycin, clindamycin 300 mg orally three times daily for 10 days (adults) or 7 mg/kg per dose three times daily for 10 days in children (maximum 300 mg/dose) is the treatment of choice, offering superior efficacy with only 1% resistance among Group A Streptococcus in the United States. 1

Critical First Step: Determine Type of Penicillin Allergy

Before selecting an antibiotic, you must distinguish between immediate and non-immediate penicillin reactions, as this fundamentally changes your treatment options 1:

• Immediate/anaphylactic reactions include anaphylaxis, angioedema, respiratory distress, or urticaria occurring within 1 hour of penicillin administration—these patients carry up to 10% cross-reactivity risk with cephalosporins and must avoid all beta-lactam antibiotics 1
• Non-immediate reactions (delayed rashes, mild reactions) carry only 0.1% cross-reactivity risk with first-generation cephalosporins 1

Treatment Algorithm Based on Allergy Profile

For Non-Immediate Penicillin Allergy (Delayed Rash, Mild Reaction)

First-generation cephalosporins are your best option despite the penicillin allergy 1:

• Cephalexin 500 mg orally twice daily for 10 days (adults) or 20 mg/kg per dose twice daily for 10 days in children (maximum 500 mg/dose) 1
• Cefadroxil 1 gram once daily for 10 days (adults) or 30 mg/kg once daily for 10 days in children (maximum 1 gram) 1
• These have strong, high-quality evidence supporting efficacy with only 0.1% cross-reactivity risk in non-immediate reactions 1, 2

For Immediate/Anaphylactic Penicillin Allergy

Clindamycin is the preferred choice 1, 3:

• Adults: 300 mg orally three times daily for 10 days 1
• Children: 7 mg/kg per dose three times daily for 10 days (maximum 300 mg/dose) 1
• Clindamycin has only ~1% resistance among Group A Streptococcus in the United States, making it more reliable than macrolides 1
• It demonstrates high efficacy in eradicating streptococci, even in chronic carriers and treatment failures 1

Alternative if Clindamycin Cannot Be Used

Clarithromycin is an acceptable second-line option 1:

• Adults: 250 mg orally twice daily for 10 days 1
• Children: 7.5 mg/kg per dose twice daily for 10 days (maximum 250 mg/dose) 1
• However, macrolide resistance is 5-8% in the United States and varies geographically, making it less reliable than clindamycin 1

Erythromycin is a less preferred alternative due to high gastrointestinal side effects 1, 4:

• 20-40 mg/kg/day divided 2-3 times daily for 10 days (maximum 1 gram per day) 1

Critical Treatment Duration Requirements

A full 10-day course is mandatory for all antibiotics to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever 1, 2:

• Shortening the course by even a few days results in appreciable increases in treatment failure rates 1
• The only exception was azithromycin (5 days), but your patient is allergic to it 1
• Treatment can be initiated up to 9 days after symptom onset and still prevent acute rheumatic fever 1, 2

Why Azithromycin Allergy Matters

Since your patient is allergic to azithromycin, this eliminates the most convenient macrolide option 1:

• Azithromycin was unique in requiring only 5 days due to its prolonged tissue half-life 1, 5
• Cross-reactivity between different macrolides (azithromycin, clarithromycin, erythromycin) is possible but not absolute—they have distinct side chain structures 1
• However, if the azithromycin allergy was severe, exercise caution with other macrolides and strongly favor clindamycin 1

Common Pitfalls to Avoid

• Do not assume all penicillin-allergic patients need to avoid cephalosporins—only those with immediate/anaphylactic reactions should avoid them, as non-immediate reactions carry only 0.1% cross-reactivity risk 1, 3
• Do not shorten the treatment course below 10 days, even if symptoms improve rapidly, as this dramatically increases treatment failure and rheumatic fever risk 1, 2
• Do not use trimethoprim-sulfamethoxazole (Bactrim)—it has 50% resistance rates and is not recommended for Group A Streptococcus 1
• Do not prescribe broad-spectrum cephalosporins (cefdinir, cefixime, cefpodoxime) when narrow-spectrum first-generation agents are appropriate, as they are more expensive and select for resistant flora 1

Adjunctive Therapy

• Acetaminophen or NSAIDs (such as ibuprofen) should be considered for moderate to severe symptoms or high fever 1, 2, 6
• Avoid aspirin in children due to Reye syndrome risk 1, 2
• Corticosteroids are not recommended as adjunctive therapy 1, 2

Special Considerations for Treatment Failures

If your patient has failed previous antibiotic courses, clindamycin is particularly effective 1:

• Clindamycin demonstrates substantially higher eradication rates than penicillin in chronic carriers and treatment failures 1
• Consider whether the patient is a chronic carrier experiencing viral pharyngitis rather than true recurrent streptococcal infections—chronic carriers generally don't require treatment 1