What is the next best antibiotic for a patient with streptococcal (strep) infection who is not responding to amoxicillin?

Next Best Antibiotic for Strep Throat When Amoxicillin Fails

If amoxicillin is truly not working for strep throat, clindamycin 300 mg orally three times daily for 10 days is the optimal next choice, as it demonstrates substantially higher eradication rates than penicillin-based antibiotics in treatment failures and chronic carriers, with only 1% resistance among Group A Streptococcus in the United States. 1, 2, 3

Critical First Step: Determine Why Amoxicillin "Isn't Working"

Before switching antibiotics, you must distinguish between three scenarios:

• True treatment failure - Patient completed full 10-day course with persistent symptoms and positive culture 2
• Poor compliance - Patient didn't complete the full course (most common reason for "failure") 2
• Chronic carrier with viral superinfection - Patient is colonized with Group A Streptococcus but experiencing repeated viral pharyngitis, which fundamentally changes management since carriers generally don't require treatment 1, 2

Why Clindamycin is Superior for Treatment Failures

Clindamycin is substantially more effective than penicillin or amoxicillin in eliminating chronic streptococcal carriage and treating persistent infections. 1, 2

• The Infectious Diseases Society of America specifically recommends clindamycin with strong, moderate-quality evidence for treatment failures and chronic carriers 1
• Clindamycin resistance remains extremely low at approximately 1% among Group A Streptococcus isolates in the United States, making it highly reliable 1, 2
• It demonstrates high efficacy even in chronic carriers who have failed multiple courses of penicillin-based therapy 1

Specific Dosing Regimen

• Adults: Clindamycin 300 mg orally three times daily for 10 days 1, 2, 3
• Pediatric patients: 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days 1
• The FDA label confirms that for β-hemolytic streptococcal infections, treatment must continue for at least 10 days 3

Alternative Options (Listed in Order of Preference)

If Clindamycin Cannot Be Used

1. Amoxicillin-clavulanate: 40 mg amoxicillin/kg/day in 3 doses (max 2000 mg amoxicillin/day) for 10 days - recommended by the Infectious Diseases Society of America for chronic carriers or treatment failures 1

2. First-generation cephalosporins (if non-anaphylactic penicillin allergy): Cephalexin 500 mg twice daily for 10 days in adults, or 20 mg/kg per dose twice daily in children 1, 2

   • Critical caveat: Do NOT use if patient had anaphylaxis, angioedema, or immediate urticaria to amoxicillin due to 10% cross-reactivity risk 1

3. Azithromycin (least preferred): 500 mg once daily for 5 days in adults, or 12 mg/kg once daily (maximum 500 mg) for 5 days in children 1, 4

   • Major limitations: 5-8% macrolide resistance in the United States (varies geographically), and lack of data proving it prevents rheumatic fever 1, 5
   • Should be reserved for situations where compliance with 10-day regimen is unlikely 1

Critical Treatment Duration Requirements

A full 10-day course is mandatory for all antibiotics except azithromycin (which requires 5 days) to achieve maximal pharyngeal eradication and prevent acute rheumatic fever. 1, 2, 3

• Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk 1, 2
• Symptoms typically resolve in 3-4 days, but completing the full course is essential for preventing complications 1

Common Pitfalls to Avoid

• Don't repeat the same antibiotic - If cephalexin or amoxicillin already failed, repeating it is unlikely to achieve better results 1
• Don't order routine post-treatment cultures - These are not recommended unless symptoms persist or special circumstances exist like history of rheumatic fever 1, 2
• Don't assume all "failures" need retreatment - Chronic carriers experiencing viral infections don't require antimicrobial therapy, as they're unlikely to spread infection or develop complications 1, 2
• Don't use trimethoprim-sulfamethoxazole (Bactrim) - It's absolutely contraindicated for strep pharyngitis because sulfonamides do not eradicate Group A Streptococcus 1

When to Consider Intramuscular Benzathine Penicillin G

If compliance with the initial course was questionable, intramuscular benzathine penicillin G 1.2 million units as a single dose may be preferable to another oral regimen. 2

When to Reevaluate for Complications

Patients with worsening symptoms after appropriate antibiotic initiation or symptoms lasting 5 days after treatment starts should be reevaluated for complications such as peritonsillar abscess, parapharyngeal abscess, or Lemierre syndrome. 2