What is the next step in treatment for a patient with strep throat who has failed amoxicillin (amox) therapy?

Treatment After Amoxicillin Failure for Strep Throat

For patients with confirmed strep throat who have failed amoxicillin therapy, switch to clindamycin as the first-line alternative, as it achieves superior eradication rates compared to repeating penicillin-based therapy. 1, 2, 3

Verify True Treatment Failure vs. Carrier State

Before initiating alternative therapy, distinguish between actual treatment failure and asymptomatic carriage:

• Symptomatic patients with persistent positive cultures warrant retreatment, while asymptomatic patients with positive cultures after completing therapy are often chronic carriers who do not require additional antibiotics 1, 2
• Carriers are unlikely to spread the organism or develop complications, and eradication is significantly more difficult in carriers than in acute infections 1
• Assess medication adherence first—poor compliance is a common cause of apparent treatment failure; if adherence is questionable, consider intramuscular benzathine penicillin G instead of oral alternatives 1, 2

Recommended Alternative Antibiotics

First-Line Alternative: Clindamycin

Clindamycin is the most effective option for penicillin/amoxicillin treatment failures:

• Achieves 100% eradication in patients who failed penicillin, compared to 36% success with repeating penicillin 3
• Dosing: Children 20-30 mg/kg/day divided into 3 doses; Adults 600 mg/day divided into 2-4 doses for 10 days 1
• Provides protection from recurrence for at least 3 months and may serve as an alternative to tonsillectomy in recurrent cases 4

Other Effective Alternatives

Amoxicillin-clavulanate overcomes beta-lactamase-producing organisms that may contribute to treatment failure:

• Children: 40 mg/kg/day divided into 3 doses; Adults: 500 mg twice daily for 10 days 1, 2
• Note that two 250-mg tablets are not equivalent to one 500-mg tablet due to different clavulanate content 1

Narrow-spectrum cephalosporins provide superior bacteriologic eradication compared to penicillin 2, 5

Macrolides (azithromycin, clarithromycin) are acceptable but have important limitations:

• 5-8% resistance rate in the United States 2
• 10 days of clarithromycin (250 mg twice daily) is more effective than 5 days of azithromycin (91% vs. 82% eradication) 6
• Bacterial failure rates of 20-25% are possible with macrolides 7

For Recurrent Treatment Failures

Benzathine penicillin G with rifampin may be beneficial when oral compliance is questionable:

• Single intramuscular dose of benzathine penicillin G plus rifampin 20 mg/kg/day orally in 2 divided doses for 4 days (maximum 600 mg/day) 1
• Rifampin is relatively contraindicated in pregnant women 1

Antibiotics to Avoid

• Tetracyclines: High prevalence of resistant strains 2
• Sulfonamides and trimethoprim-sulfamethoxazole: Do not eradicate GAS 2
• Fluoroquinolones: Older agents (ciprofloxacin) have limited GAS activity; newer agents (levofloxacin, moxifloxacin) are unnecessarily broad-spectrum and expensive 2

Follow-Up and Monitoring

Post-treatment cultures are indicated only in specific circumstances:

• Patients who remain symptomatic after completing therapy 2
• Patients with recurrent symptoms 2
• Patients with a history of rheumatic fever 2
• Cultures should be performed 2-7 days after completion of therapy 2

Do not routinely retest asymptomatic patients who have completed therapy, as many are chronic carriers who do not require further treatment 1, 2

Special Considerations for Persistent Failures

Screen household contacts when eradication attempts repeatedly fail:

• Close personal contacts can be the source of reinfection to patients 1
• If family members are symptomatic, swabbing and treatment should be coordinated with their primary care provider 1
• Consider screening asymptomatic close contacts when failure of eradication or recolonization occurs 1

Consider pet screening in complex cases where household contacts screen negative, as pets have been implicated in reinfection 1, 2

Common Pitfalls to Avoid

• Treating asymptomatic carriers: This is difficult, often unsuccessful, and unnecessary unless preventing rheumatic fever recurrence 1
• Inadequate treatment duration: Ensure completion of full 10-day courses for most regimens 1, 7
• Ignoring compliance issues: Consider intramuscular therapy when adherence is questionable rather than cycling through multiple oral agents 1, 2
• Premature follow-up cultures: Wait at least 24 hours after completing treatment before obtaining clearance cultures 1