What is the alternative treatment for a patient with streptococcal (strep) infection who has a penicillin allergy?

Treatment of Streptococcal Infection in Penicillin-Allergic Patients

For patients with streptococcal infection and penicillin allergy, the treatment choice depends critically on whether the allergy was immediate/anaphylactic: use first-generation cephalosporins (cephalexin or cefadroxil) for non-immediate reactions, but switch to clindamycin for immediate/anaphylactic reactions. 1

Critical First Step: Classify the Penicillin Allergy Type

You must determine if the patient had an immediate/anaphylactic reaction before selecting an antibiotic. 1, 2

• Immediate/anaphylactic reactions include: anaphylaxis, angioedema, respiratory distress, or urticaria occurring within 1 hour of penicillin administration 3, 1
• Non-immediate reactions include: delayed rashes, mild gastrointestinal symptoms, or other non-life-threatening reactions 1
• The cross-reactivity risk with cephalosporins is only 0.1% for non-immediate reactions but up to 10% for immediate/anaphylactic reactions 1, 2

Treatment Algorithm Based on Allergy Type

For Non-Immediate Penicillin Allergy (Safe to Use Cephalosporins)

First-generation cephalosporins are the preferred first-line alternatives with strong, high-quality evidence. 1

Adults:

• Cephalexin 500 mg orally every 12 hours for 10 days 1
• Alternative: Cefadroxil 1 gram orally once daily for 10 days 1

Children:

• Cephalexin 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days 1
• Alternative: Cefadroxil 30 mg/kg once daily (maximum 1 gram) for 10 days 1

Rationale: First-generation cephalosporins have narrow spectrum, proven efficacy, and low cost compared to alternatives. 1

For Immediate/Anaphylactic Penicillin Allergy (Must Avoid All Beta-Lactams)

Clindamycin is the preferred first-line alternative for immediate/anaphylactic penicillin allergy. 2

Dosing:

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

Why clindamycin is preferred:

• Demonstrates high efficacy in eradicating streptococci, even in chronic carriers 1, 2
• Only approximately 1% resistance among Group A Streptococcus in the United States 1, 2
• More reliable than macrolides in areas with resistance concerns 2

Acceptable alternative: Azithromycin

• Adults: 500 mg orally once daily for 5 days 1, 2
• Children: 12 mg/kg once daily (maximum 500 mg) for 5 days 1, 2, 4
• Important caveat: Azithromycin has 5-8% macrolide resistance in the United States 1, 2, and data establishing efficacy in preventing rheumatic fever are not available 4

Other macrolide option:

• Clarithromycin 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days 1
• Same resistance concerns as azithromycin 1

Critical Treatment Duration Requirements

All antibiotics except azithromycin require a full 10-day course to achieve maximal pharyngeal eradication and prevent acute rheumatic fever. 1, 2

• Azithromycin is the only exception, requiring only 5 days due to its prolonged tissue half-life 1, 2, 4
• Shortening the course by even a few days results in appreciable increases in treatment failure rates 1
• The primary goal is not just symptomatic improvement but prevention of acute rheumatic fever, which requires adequate bacterial eradication 1

Common Pitfalls to Avoid

Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to the 10% cross-reactivity risk—this is a critical safety consideration. 1, 2

Do not prescribe azithromycin as first-line therapy when penicillin or preferred alternatives can be used—it should be reserved for patients with documented penicillin allergy who cannot tolerate other options. 1

Do not shorten treatment courses below 10 days (except for azithromycin's 5-day regimen) despite clinical improvement, as this increases treatment failure and rheumatic fever risk. 1, 2

Be aware of local macrolide resistance patterns before prescribing azithromycin or clarithromycin, as resistance varies geographically and can lead to treatment failure. 1, 2

Do not assume all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them. 1

Adjunctive Therapy

For symptom management:

• Use acetaminophen or NSAIDs (ibuprofen) for moderate to severe symptoms or high fever 1, 2
• Avoid aspirin in children due to risk of Reye syndrome 1, 2
• Do not use corticosteroids as adjunctive therapy 1, 2

Special Considerations for Group B Streptococcus (Intrapartum Prophylaxis)

For pregnant women requiring intrapartum antibiotic prophylaxis:

• Non-immediate penicillin allergy: Use cefazolin 3, 1
• Immediate/anaphylactic penicillin allergy: Use clindamycin or vancomycin depending on susceptibility testing 3, 1
• Antimicrobial susceptibility testing should be ordered for antenatal GBS cultures in penicillin-allergic women at high risk for anaphylaxis 3