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

Treatment of Streptococcal Pharyngitis in Penicillin-Allergic Patients

For patients with non-immediate (non-anaphylactic) penicillin allergy, use a first-generation cephalosporin such as cephalexin 500 mg orally twice daily for 10 days; for patients with immediate/anaphylactic penicillin reactions, use clindamycin 300 mg orally three times daily for 10 days as the preferred alternative. 1

Critical First Step: Determine the Type of Penicillin Allergy

The treatment algorithm hinges entirely on whether the patient experienced an immediate versus non-immediate reaction to penicillin:

• Immediate/anaphylactic reactions include anaphylaxis, angioedema, respiratory distress, or urticaria occurring within 1 hour of penicillin administration 1
• Non-immediate reactions include delayed rashes, mild gastrointestinal symptoms, or other non-life-threatening symptoms occurring hours to days after exposure 1
• Up to 10% cross-reactivity exists between penicillin and cephalosporins in patients with immediate hypersensitivity, making all beta-lactams unsafe in this group 2, 1

Treatment Algorithm for Non-Immediate Penicillin Allergy

First-generation cephalosporins are the preferred choice with strong, high-quality evidence supporting their efficacy 2, 1:

• Cephalexin: 500 mg orally every 12 hours for 10 days in adults 1
• Cefadroxil: 30 mg/kg once daily (maximum 1 gram) for 10 days 1
• Cross-reactivity risk is only 0.1% in patients with non-severe, delayed penicillin reactions 1
• These agents have narrow spectrum, proven efficacy, and low cost 1

Treatment Algorithm for Immediate/Anaphylactic Penicillin Allergy

All beta-lactam antibiotics must be avoided in patients with immediate hypersensitivity reactions 2, 1. The preferred alternatives are:

First-Line: Clindamycin (Preferred)

• Dosing: 300 mg orally three times daily for 10 days in adults; 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days in children 2, 1
• Evidence: Strong, moderate-quality evidence for efficacy 2, 1
• Resistance: Approximately 1% resistance rate among Group A Streptococcus in the United States 1
• Advantages: Highly effective even in chronic carriers who have failed penicillin treatment 2, 1

Second-Line: Azithromycin

• Dosing: 500 mg orally once daily for 5 days in adults; 12 mg/kg once daily (maximum 500 mg) for 5 days in children 2, 1, 3
• Evidence: Strong, moderate-quality evidence but with important limitations 2, 1
• Resistance: 5-8% macrolide resistance in the United States, varying geographically 2, 1
• Unique feature: Only antibiotic requiring just 5 days due to prolonged tissue half-life 2, 1
• FDA indication: Approved for pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy 3

Third-Line: Clarithromycin

• Dosing: 250 mg orally twice daily for 10 days in adults; 7.5 mg/kg per dose twice daily (maximum 250 mg/dose) for 10 days in children 2, 1
• Evidence: Strong, moderate-quality evidence 2, 1
• Resistance: Same 5-8% macrolide resistance concerns as azithromycin 2, 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 2, 1:

• Shortening the course by even a few days results in appreciable increases in treatment failure rates 1
• Azithromycin requires only 5 days due to its unique pharmacokinetics and prolonged tissue half-life 2, 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 immediate/anaphylactic penicillin allergy

• Patients with anaphylaxis, angioedema, or immediate urticaria to penicillin must avoid all cephalosporins due to 10% cross-reactivity risk 2, 1
• This is a critical safety consideration that cannot be overlooked 1

Do NOT assume all penicillin-allergic patients cannot receive cephalosporins

• Only those with immediate/anaphylactic reactions should avoid them 1
• Patients with non-immediate reactions can safely receive first-generation cephalosporins with only 0.1% cross-reactivity risk 1

Do NOT use macrolides as first-line when cephalosporins can be used

• Macrolides should be reserved for true immediate/anaphylactic penicillin allergy 1
• Geographic variation in macrolide resistance (5-8% in the US) makes clindamycin more reliable 2, 1

Do NOT prescribe shorter courses than recommended

• Except for azithromycin's 5-day regimen, all antibiotics require the full 10 days 2, 1
• Shortening courses dramatically increases treatment failure and rheumatic fever risk 1

Do NOT use trimethoprim-sulfamethoxazole (Bactrim)

• High resistance rates (50%) and not recommended for Group A Streptococcus 1

Adjunctive Therapy

For symptom management, consider the following adjuncts 2, 1:

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

Special Considerations for Recurrent Infections

• Patients with recurrent streptococcal pharyngitis may be experiencing either multiple true infections or may be chronic carriers experiencing viral infections 2, 1
• Clindamycin may be particularly effective for recurrent infections due to its ability to eradicate streptococci in chronic carriers 1, 4
• Chronic carriers generally do not require antimicrobial therapy, as they are unlikely to spread disease and are at little risk for complications 1

Post-Treatment Testing

• Routine follow-up throat cultures or rapid antigen detection tests are not recommended for asymptomatic patients who have completed therapy 2, 1
• Testing should only be considered in special circumstances, such as patients with a history of rheumatic fever 1