What are the recommended courses of antibiotics (abx) for streptococcal infections in patients allergic to Penicillin (PCN)?

Antibiotic Treatment for Streptococcal Infections in Penicillin-Allergic Patients

For penicillin-allergic patients with streptococcal pharyngitis, use clindamycin 7 mg/kg three times daily for 10 days if the allergy is immediate/anaphylactic, or first-generation cephalosporins (cephalexin 20 mg/kg twice daily for 10 days) if the allergy is non-immediate. 1

Treatment Algorithm Based on Allergy Type

Non-Immediate (Delayed) Penicillin Allergy

First-generation cephalosporins are the preferred first-line alternatives for patients without immediate hypersensitivity reactions (no anaphylaxis, angioedema, respiratory distress, or urticaria). 1, 2

• Cephalexin: 20 mg/kg per dose twice daily (maximum 500 mg/dose) for 10 days 1
• Cefadroxil: 30 mg/kg once daily (maximum 1 gram) for 10 days 1
• These agents have strong, high-quality evidence supporting their efficacy 1
• Cross-reactivity risk with penicillin is minimal in non-immediate allergies 2

Immediate/Anaphylactic Penicillin Allergy

Avoid all beta-lactams (including cephalosporins) due to up to 10% cross-reactivity risk. 1 Use the following alternatives:

First-Line: Clindamycin

• Dosing: 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days 1, 2
• Rationale: Strong, moderate-quality evidence with high efficacy in eradicating streptococci, even in chronic carriers 1
• Resistance: Approximately 1% resistance among Group A Streptococcus isolates in the United States 1

Alternative: Macrolides

Azithromycin:

• Dosing: 12 mg/kg once daily (maximum 500 mg) for 5 days 1, 3
• Unique advantage: Only requires 5 days due to prolonged tissue half-life 1, 3
• Clinical efficacy: 95% bacteriologic eradication and 98% clinical success at Day 14 in comparative trials 3
• FDA-approved specifically for streptococcal pharyngitis as alternative to first-line therapy 3

Clarithromycin:

• Dosing: 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days 1
• Evidence: Strong, moderate-quality evidence 1

Erythromycin:

• Dosing: 20-40 mg/kg/day divided 2-3 times daily for 10 days 2
• Limitation: Substantially higher gastrointestinal side effects compared to azithromycin or clarithromycin 1

Critical 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, 2 Azithromycin is the only exception, requiring only 5 days due to its unique pharmacokinetics. 1, 3

Resistance Considerations

• Macrolide resistance: Approximately 5-8% among pharyngeal isolates in the United States 1
• Clindamycin resistance: Approximately 1% among Group A Streptococcus isolates 1
• Be aware of local resistance patterns when prescribing macrolides, as resistance varies geographically and temporally 1
• Susceptibility testing should be performed when treating with azithromycin, as some strains are resistant 3

Common Pitfalls to Avoid

• Do NOT use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to 10% cross-reactivity risk 1
• Do NOT prescribe shorter courses than recommended (except azithromycin), as this leads to treatment failure and complications including rheumatic fever 1
• Do NOT assume all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them 1
• Do NOT use trimethoprim-sulfamethoxazole for streptococcal pharyngitis due to high resistance rates and lack of efficacy 1
• Do NOT use tetracyclines or sulfonamides due to frequent treatment failures even with susceptible organisms 2

Adjunctive Therapy

• Acetaminophen or NSAIDs may be used for moderate to severe symptoms or high fever 1
• Avoid aspirin in children due to risk of Reye syndrome 1
• Do NOT use corticosteroids as adjunctive therapy 1

Special Considerations

• Routine post-treatment throat cultures are not recommended for asymptomatic patients who have completed therapy 1, 2
• For recurrent streptococcal pharyngitis, clindamycin may be particularly effective due to its ability to eradicate the organism in chronic carriers 1
• Data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available, though it is FDA-approved for streptococcal pharyngitis 3