What is the next recommended antibiotic for patients with a positive strep test after a course of amoxicillin (amoxicillin)?

Treatment After Amoxicillin Failure for Group A Streptococcal Pharyngitis

For patients with persistent positive strep after completing amoxicillin, clindamycin 300 mg three times daily for 10 days (or 7 mg/kg per dose three times daily in children) is the recommended next antibiotic, as it demonstrates superior eradication rates in treatment failures and has only ~1% resistance among Group A Streptococcus in the United States. 1, 2, 3

Understanding the Clinical Scenario

When a patient remains strep-positive after amoxicillin, you must distinguish between treatment failure versus chronic carrier state with a new viral infection. This distinction is critical:

• True treatment failure presents with persistent or worsening symptoms and positive culture of the same serotype 4
• Chronic carriers are asymptomatic but harbor Group A Streptococcus, often experiencing concurrent viral infections that cause symptoms 2, 3

First-Line Recommendation: Clindamycin

Clindamycin is the preferred choice for amoxicillin treatment failures based on multiple compelling factors:

• Superior eradication rates: In patients with bacterial failure after penicillin, clindamycin achieved 100% eradication (26/26 patients) compared to only 36% with repeat penicillin therapy (8/22 patients) 4
• Minimal resistance: Approximately 1% resistance rate among Group A Streptococcus isolates in the United States 2, 3
• Strong evidence for chronic carriers: Clindamycin demonstrates high efficacy in eradicating streptococci even in chronic carrier states 1, 2

Dosing Regimen

• Adults: 300 mg orally three times daily for 10 days 1, 2, 3
• Children: 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days 1, 2, 3

Alternative Option: Amoxicillin-Clavulanate

If clindamycin cannot be used, amoxicillin-clavulanate is an acceptable alternative for chronic carriers:

• Dosing: 40 mg amoxicillin/kg per day in three divided doses (maximum 2,000 mg amoxicillin per day) for 10 days 1
• Rationale: The beta-lactamase inhibitor (clavulanate) may overcome bacterial resistance mechanisms that contributed to initial treatment failure 1
• Evidence quality: Strong recommendation with moderate-quality evidence for chronic carrier treatment 1

When to Consider Macrolides (Use with Caution)

Azithromycin or clarithromycin should only be considered if both clindamycin and amoxicillin-clavulanate are contraindicated, due to resistance concerns:

• Macrolide resistance: Approximately 5-8% in the United States, but varies geographically and can be higher in other regions 2, 3, 5
• Comparative efficacy: 10 days of clarithromycin (250 mg twice daily) achieved 91% eradication versus 82% with 5 days of azithromycin (P=0.012) 5
• If using azithromycin: 500 mg once daily for adults (12 mg/kg once daily for children, maximum 500 mg) for 5 days 1, 2, 6
• If using clarithromycin: 250 mg twice daily for adults (7.5 mg/kg per dose twice daily for children, maximum 250 mg per dose) for 10 days 1, 2

Critical Treatment Duration

A full 10-day course is essential for all antibiotics except azithromycin to achieve maximal pharyngeal eradication and prevent complications including acute rheumatic fever 1, 2, 3. Azithromycin requires only 5 days due to its prolonged tissue half-life 1, 2, 6.

Common Pitfalls to Avoid

• Do not simply repeat amoxicillin: Studies show only 36% success with repeat penicillin/amoxicillin therapy after initial failure, compared to 100% with clindamycin 4
• Do not use first-generation cephalosporins: These are appropriate for penicillin-allergic patients, but not for treatment failures after amoxicillin, as cross-resistance may exist 2, 3
• Do not assume all positive cultures require treatment: Asymptomatic patients who completed therapy may be chronic carriers experiencing a viral infection and generally do not require retreatment 2, 3
• Do not prescribe shorter courses: Even if symptoms improve, completing the full course prevents complications and reduces relapse risk 1, 2

When to Consider Chronic Carrier State

Routine post-treatment cultures are not recommended for asymptomatic patients who have completed therapy 2, 3. Consider chronic carrier status if:

• Patient is asymptomatic but culture remains positive 2, 3
• Multiple recurrences despite appropriate therapy 1, 2
• Household contacts have recurrent infections 1

Chronic carriers generally do not require antimicrobial therapy unless they are spreading infection to others or have special circumstances (e.g., history of rheumatic fever) 2, 3.