What is the recommended treatment for a patient with a streptococcal (strep) infection and a penicillin (PCN) allergy?

Treatment for Streptococcal Infections with Penicillin Allergy

For patients with non-immediate (non-anaphylactic) penicillin allergy, first-generation cephalosporins such as cephalexin 500 mg twice daily for 10 days are the preferred first-line alternative; for patients with immediate/anaphylactic penicillin allergy, clindamycin 300 mg three times daily for 10 days is the treatment of choice. 1, 2

Critical First Step: Determine the Type of Penicillin Allergy

The type of allergic reaction dictates which antibiotics are safe versus contraindicated:

• Immediate/anaphylactic reactions include anaphylaxis, angioedema, respiratory distress, or urticaria occurring within 1 hour of penicillin administration—these patients must avoid ALL beta-lactam antibiotics including cephalosporins due to up to 10% cross-reactivity risk 1, 3

• Non-immediate reactions include delayed rashes, mild gastrointestinal symptoms, or other non-severe reactions occurring after 1 hour—these patients can safely receive first-generation cephalosporins with only 0.1% cross-reactivity risk 1

Treatment Algorithm Based on Allergy Type

For Non-Immediate Penicillin Allergy (Preferred Option)

First-generation cephalosporins are the preferred choice with strong, high-quality evidence:

• Cephalexin: 500 mg orally twice daily for 10 days (pediatric: 20 mg/kg per dose twice daily, maximum 500 mg/dose) 1, 2
• Cefadroxil: 1 gram orally once daily for 10 days (pediatric: 30 mg/kg once daily, maximum 1 gram) 1, 2

These agents offer narrow spectrum, proven efficacy comparable to penicillin, and low cost 1, 2

For Immediate/Anaphylactic Penicillin Allergy

Clindamycin is the preferred alternative with strong, moderate-quality evidence:

• Clindamycin: 300 mg orally three times daily for 10 days (pediatric: 7 mg/kg per dose three times daily, maximum 300 mg/dose) 1, 2
• Clindamycin has approximately 1% resistance rate among Group A Streptococcus in the United States 1
• Particularly effective in chronic streptococcal carriers who have failed penicillin treatment 1

Alternative macrolide options (with important caveats):

• Azithromycin: 500 mg orally once daily for 5 days (pediatric: 12 mg/kg once daily, maximum 500 mg) 1, 2, 4

  • Only antibiotic requiring just 5 days due to prolonged tissue half-life 1, 2
  • Macrolide resistance is 5-8% in the United States, varying geographically 1, 2

• Clarithromycin: 250 mg orally twice daily for 10 days (pediatric: 7.5 mg/kg per dose twice daily, maximum 250 mg/dose) 1, 2

• Erythromycin: 250-500 mg orally every 6-12 hours for 10 days (pediatric: 20-40 mg/kg/day divided 2-3 times daily) 1

  • Less preferred due to high rate of gastrointestinal side effects 1

Critical Treatment Duration Requirements

A full 10-day course is essential for all antibiotics EXCEPT azithromycin to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever. 1, 2, 3

• Shortening the course by even a few days results in appreciable increases in treatment failure rates 1
• Azithromycin is the only exception, requiring only 5 days due to its unique pharmacokinetics 1, 2, 4

Common Pitfalls to Avoid

• Do NOT use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to 10% cross-reactivity risk—this is a critical safety consideration 1, 3

• Do NOT assume all penicillin-allergic patients cannot receive cephalosporins—only those with immediate/anaphylactic reactions should avoid them; patients with non-immediate reactions can safely receive first-generation cephalosporins 1, 2

• Do NOT prescribe shorter courses than recommended (except azithromycin's 5-day regimen) as this leads to treatment failure and complications including acute rheumatic fever 1, 2

• Do NOT use trimethoprim-sulfamethoxazole (Bactrim) for strep throat due to approximately 50% resistance rates among Group A Streptococcus 1, 2

• Do NOT use broad-spectrum cephalosporins (second or third generation) when narrow-spectrum first-generation agents are appropriate—they are more expensive and more likely to select for antibiotic-resistant flora 1

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

Adjunctive Therapy

• Acetaminophen or NSAIDs (such as ibuprofen) should be considered for moderate to severe symptoms or control of high fever 1
• Avoid aspirin in children due to risk of Reye syndrome 1
• Do NOT use corticosteroids as adjunctive therapy 1

Special Considerations

• Patients become non-contagious after 24 hours of appropriate antibiotic therapy 2
• Routine post-treatment throat cultures are not recommended for asymptomatic patients who have completed therapy 1
• For patients with recurrent streptococcal pharyngitis, clindamycin may be particularly effective due to its ability to eradicate the organism in chronic carriers 1, 3
• Most patients reporting penicillin allergy (90-97%) do not have a true allergy and could potentially receive cephalosporins safely after appropriate allergy evaluation 5, 6