What are the first and second line treatments for strep (streptococcal) pharyngitis in a pediatric or young adult patient, including those with a penicillin allergy?

First and Second Line Treatment for Strep Pharyngitis

First-Line Treatment

Penicillin or amoxicillin for 10 days remains the gold standard first-line treatment for strep pharyngitis in patients without penicillin allergy, due to proven efficacy, zero documented resistance worldwide, narrow spectrum, safety, and low cost. 1, 2

Specific Dosing Regimens

For pediatric patients:

• Amoxicillin 50 mg/kg once daily (maximum 1000 mg) for 10 days is the preferred regimen due to enhanced adherence while maintaining equivalent efficacy 3
• Alternative: Amoxicillin 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days 3
• Penicillin V 250 mg twice daily for 10 days is also acceptable 4

For adults:

• Penicillin or amoxicillin for 10 days, with specific dosing based on formulation 1, 2

Critical Treatment Duration

• A full 10-day course is mandatory regardless of symptom resolution to achieve maximal pharyngeal eradication and prevent acute rheumatic fever 3, 1
• Shortening the course by even a few days results in appreciable increases in treatment failure rates 1
• Therapy can be safely postponed up to 9 days after symptom onset and still prevent acute rheumatic fever 3

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Second-Line Treatment (Penicillin-Allergic Patients)

The choice of second-line antibiotic depends critically on the type of penicillin allergy—this distinction is essential for safe and effective treatment.

For Non-Immediate (Non-Anaphylactic) Penicillin Allergy

First-generation cephalosporins are the preferred second-line alternatives, with strong, high-quality evidence supporting their efficacy. 5, 3

Specific regimens:

• Cephalexin 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days 5, 3
• Cefadroxil 30 mg/kg once daily (maximum 1 gram) for 10 days 5, 3

Key safety consideration:

• Cross-reactivity risk with first-generation cephalosporins is only 0.1% in patients with non-severe, delayed penicillin reactions 5

For Immediate/Anaphylactic Penicillin Allergy

Patients with immediate hypersensitivity reactions (anaphylaxis, angioedema, respiratory distress, or urticaria within 1 hour) must avoid ALL beta-lactam antibiotics, including cephalosporins, due to up to 10% cross-reactivity risk. 5, 3

Preferred alternative: Clindamycin

• Clindamycin 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days 5, 3
• Adults: 300 mg three times daily for 10 days 5
• Clindamycin has strong, moderate-quality evidence with only ~1% resistance among Group A Streptococcus in the United States 5
• Particularly effective in chronic carriers and treatment failures 5

Acceptable alternatives: Macrolides

• Azithromycin 12 mg/kg once daily (maximum 500 mg) for 5 days 5, 3, 6

  • Only antibiotic requiring just 5 days due to prolonged tissue half-life 5
  • However, macrolide resistance is 5-8% in the United States 5
  • FDA label specifically notes: "Data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available" 6

• Clarithromycin 7.5 mg/kg per dose twice daily (maximum 250 mg per dose) for 10 days 5, 3

  • Similar resistance concerns as azithromycin 5

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Critical Pitfalls to Avoid

• Never prescribe cephalosporins to patients with immediate/anaphylactic penicillin reactions due to 10% cross-reactivity risk 5, 3
• Never shorten the 10-day course (except azithromycin's 5-day regimen) as this dramatically increases treatment failure and rheumatic fever risk 3, 1
• Never use broad-spectrum cephalosporins (cefaclor, cefuroxime, cefixime, cefdinir, cefpodoxime) when narrow-spectrum first-generation agents are appropriate—they are more expensive and select for resistant flora 5, 3
• Never use trimethoprim-sulfamethoxazole, tetracyclines, or sulfonamides as they are ineffective for Group A Streptococcus eradication 5, 3
• Never use azithromycin as first-line therapy when penicillin or amoxicillin can be used—it should be reserved for documented penicillin allergy 5

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Adjunctive Therapy

• Acetaminophen or NSAIDs (ibuprofen) should be offered to all patients for moderate to severe symptoms or high fever 5, 3, 1
• Aspirin must be avoided in children due to Reye syndrome risk 5, 3
• Corticosteroids are not recommended as adjunctive therapy 5

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Treatment Algorithm Summary

1. Confirm diagnosis with rapid antigen detection test or throat culture before treating 1

2. Assess for penicillin allergy:

   • No allergy: Amoxicillin 50 mg/kg once daily × 10 days (preferred) 3
   • Non-immediate allergy: Cephalexin 20 mg/kg twice daily × 10 days 5, 3
   • Immediate/anaphylactic allergy: Clindamycin 7 mg/kg three times daily × 10 days (preferred) or azithromycin 12 mg/kg once daily × 5 days 5, 3

3. Ensure full treatment course completion (10 days for all except azithromycin) 3, 1

4. Add analgesic therapy (acetaminophen or ibuprofen) for symptom control 5, 3, 1