What is the recommended treatment for a patient with streptococcal (strep) pharyngitis who has received amoxicillin in the last 90 days?

Treatment of Streptococcal Pharyngitis with Recent Amoxicillin Exposure

For patients with streptococcal pharyngitis who received amoxicillin in the last 90 days, switch to a first-generation cephalosporin (cephalexin 500 mg twice daily for 10 days in adults, or 20 mg/kg/dose twice daily in children) if there is no history of immediate penicillin allergy, or use clindamycin (300 mg three times daily for 10 days in adults, or 7 mg/kg/dose three times daily in children) if there is immediate/anaphylactic penicillin allergy. 1

Rationale for Avoiding Repeat Amoxicillin

While the 2012 IDSA guidelines establish penicillin and amoxicillin as first-line therapy for streptococcal pharyngitis 2, recent amoxicillin exposure within 90 days raises concerns about:

• Potential selection of resistant oral flora that may interfere with treatment efficacy
• Increased risk of treatment failure when the same antibiotic class is used repeatedly in short succession
• Need for broader antimicrobial coverage to address potential beta-lactamase producing organisms in the oropharynx

Treatment Algorithm Based on Allergy History

For Non-Immediate (Non-Anaphylactic) Penicillin Allergy or No Allergy

First-generation cephalosporins are the preferred alternative when avoiding repeat amoxicillin exposure 1:

• Cephalexin: 500 mg orally twice daily for 10 days (adults) or 20 mg/kg/dose twice daily for 10 days (children, maximum 500 mg/dose) 1, 3
• Cefadroxil: 30 mg/kg once daily for 10 days (children) 1
• Cross-reactivity risk is only 0.1% in patients with non-severe, delayed penicillin reactions 1

For Immediate/Anaphylactic Penicillin Allergy

Clindamycin is the preferred choice due to superior efficacy and lower resistance rates 1:

• Dosing: 300 mg orally three times daily for 10 days (adults) or 7 mg/kg/dose three times daily for 10 days (children, maximum 300 mg/dose) 1, 3
• Resistance rate: Only ~1% among Group A Streptococcus in the United States 1, 3
• Efficacy: Demonstrates high eradication rates even in chronic carriers 1
• Critical advantage: Clindamycin is particularly effective in patients who have failed previous penicillin treatment 1

Alternative: Azithromycin (Less Preferred)

Azithromycin may be considered when compliance with a 10-day regimen is unlikely 1:

• Dosing: 500 mg on day 1, then 250 mg once daily for days 2-5 (adults) or 12 mg/kg once daily for 5 days (children, maximum 500 mg) 1, 4
• Major limitation: 5-8% macrolide resistance in the United States, with geographic variation 1
• Bacteriologic inferiority: A 2001 study demonstrated that 10 days of clarithromycin achieved 91% eradication versus only 82% with 5 days of azithromycin (P=0.012) 5

Critical Treatment Duration Requirements

A full 10-day course is essential for all antibiotics except azithromycin to achieve maximal pharyngeal eradication and prevent acute rheumatic fever 1, 6, 3:

• Azithromycin requires only 5 days due to its prolonged tissue half-life 1, 6
• Shortening courses below 10 days (except azithromycin) dramatically increases treatment failure rates 6
• The primary goal is prevention of acute rheumatic fever, which requires adequate bacterial eradication 1

Common Pitfalls to Avoid

• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to up to 10% cross-reactivity risk 1
• Do not prescribe azithromycin as first-line when cephalosporins or clindamycin can be used, given the 5-8% resistance rate 1, 3
• Do not shorten the antibiotic course below 10 days (except for azithromycin's 5-day regimen) as this increases treatment failure and rheumatic fever risk 1, 6
• Do not use trimethoprim-sulfamethoxazole (Bactrim) for streptococcal pharyngitis due to high resistance rates and lack of efficacy 1

Adjunctive Symptomatic Management

• Acetaminophen or NSAIDs (ibuprofen) for moderate to severe symptoms or high fever 1, 3
• Avoid aspirin in children due to Reye syndrome risk 1, 6
• Corticosteroids are not recommended as adjunctive therapy 1

Follow-Up Considerations

• Routine post-treatment cultures are not recommended for asymptomatic patients who completed therapy 2, 1
• Consider follow-up testing only in special circumstances, such as patients with a history of rheumatic fever 1
• Patients with recurrent episodes should be evaluated to determine whether they are experiencing true recurrent infections or are chronic carriers with viral infections 1, 6