What antibiotic should be prescribed for a patient with a positive rapid strep (streptococcal) test who is allergic to penicillin?

Treatment for Positive Rapid Strep with Penicillin Allergy

For patients with non-immediate (non-anaphylactic) penicillin allergy, prescribe a first-generation cephalosporin such as cephalexin 500 mg twice daily for 10 days in adults or 20 mg/kg per dose twice daily for 10 days in children. 1, 2, 3

For patients with immediate/anaphylactic penicillin allergy (hives, angioedema, bronchospasm within 1 hour), prescribe clindamycin 300 mg three times daily for 10 days in adults or 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days in children. 1, 3

Critical First Step: Determine Type of Penicillin Allergy

Before prescribing, you must distinguish between immediate and non-immediate reactions 1:

• 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 after 1 hour 1

This distinction is critical because up to 10% of patients with immediate hypersensitivity to penicillin have cross-reactivity with first-generation cephalosporins, making cephalosporins unsafe for this group 1, 2, 3

Treatment Algorithm

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

First-line choice: First-generation cephalosporins 1, 2, 3

• Cephalexin: 500 mg orally twice daily for 10 days (adults) or 20 mg/kg per dose twice daily for 10 days (children, maximum 500 mg/dose) 1, 3
• Cefadroxil: 1 gram orally once daily for 10 days (adults) or 30 mg/kg once daily for 10 days (children, maximum 1 gram) 1, 3

Why this is preferred: First-generation cephalosporins have strong, high-quality evidence supporting their efficacy, with only 0.1% cross-reactivity risk in patients with non-severe, delayed penicillin reactions 1, 3. They are narrow-spectrum, cost-effective, and highly effective at eradicating Group A Streptococcus 1, 3.

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

First-line choice: Clindamycin 1, 3, 4

• Clindamycin: 300 mg orally three times daily for 10 days (adults) or 7 mg/kg per dose three times daily for 10 days (children, maximum 300 mg/dose) 1, 3, 4

Why clindamycin is preferred over macrolides: Clindamycin has approximately 1% resistance among Group A Streptococcus isolates in the United States, compared to 5-8% macrolide resistance 1, 3. Clindamycin also demonstrates high efficacy in eradicating streptococci, even in chronic carriers 1.

Alternative: Azithromycin (if clindamycin cannot be used) 1, 3, 5

• Azithromycin: 500 mg orally once daily for 5 days (adults) or 12 mg/kg once daily for 5 days (children, maximum 500 mg) 1, 3, 5

Important caveat about azithromycin: While azithromycin is FDA-approved for streptococcal pharyngitis and requires only 5 days of treatment due to its prolonged tissue half-life 1, 5, it should be reserved for patients who cannot tolerate clindamycin 1. Macrolide resistance is 5-8% in the United States but can be higher in other geographic regions 1, 3. The FDA label specifically states azithromycin is indicated "as an alternative to first-line therapy in individuals who cannot use first-line therapy" 5.

Other macrolide options (less preferred than clindamycin): 1

• Clarithromycin: 250 mg orally twice daily for 10 days (adults) or 7.5 mg/kg per dose twice daily for 10 days (children, maximum 250 mg/dose) 1
• Erythromycin: 250-500 mg every 6-12 hours for 10 days (adults) or 20-40 mg/kg/day divided 2-3 times daily for 10 days (children) - less preferred due to gastrointestinal side effects 1

Critical Treatment 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, 3 Shortening the course by even a few days results in appreciable increases in treatment failure rates 2.

Azithromycin is the only exception, requiring only 5 days due to its unique pharmacokinetics and prolonged tissue half-life. 1, 3, 5

Common Pitfalls to Avoid

• Do not prescribe cephalosporins to patients with immediate/anaphylactic penicillin reactions (anaphylaxis, angioedema, urticaria within 1 hour) due to the 10% cross-reactivity risk 1, 2, 3
• Do not shorten the treatment course below 10 days (except for azithromycin's 5-day regimen) despite clinical improvement, as this increases treatment failure rates and risk of acute rheumatic fever 1, 2
• Do not use azithromycin as first-line therapy - it should only be used when penicillin and preferred alternatives (cephalosporins or clindamycin) cannot be used 1
• Do not assume all penicillin-allergic patients cannot receive cephalosporins - only those with immediate/anaphylactic reactions should avoid them 2
• Be aware of local macrolide resistance patterns before prescribing azithromycin or clarithromycin, as resistance varies geographically 1, 3

Adjunctive Therapy

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

Post-Treatment Considerations

• Routine post-treatment throat cultures are not recommended for asymptomatic patients who have completed therapy 1, 2
• Follow-up testing should only be considered in special circumstances, such as patients with a history of rheumatic fever 1, 2