Alternative Antibiotics for Strep Throat Not Responding to Amoxicillin
For strep throat (streptococcal pharyngitis) that is not responding to amoxicillin, switch to clindamycin, cephalosporins, or macrolides as second-line therapy. 1
First-Line Treatment Failure
When a patient with streptococcal pharyngitis fails to respond to amoxicillin after 3-5 days of treatment, this constitutes treatment failure and requires a change in antibiotic therapy. Treatment failure rates with penicillin/amoxicillin have increased over time and are now reported to be approximately 30% 2.
Causes of Treatment Failure
- Poor medication compliance with the 10-day regimen
- Reexposure to Streptococcus-infected family members
- Bacterial co-pathogenicity
- Penicillin tolerance
- Bacterial resistance
Second-Line Treatment Options
1. Cephalosporins (Preferred Option)
- High-dose amoxicillin-clavulanate: 90 mg/kg amoxicillin and 6.4 mg/kg clavulanate, not exceeding 2g every 12 hours 3
- Cefuroxime axetil: Adult dose 250-500 mg twice daily for 10 days 3
- Cephalexin: 20 mg/kg twice daily (maximum 500 mg per dose) for 10 days 1
Cephalosporins have been demonstrated to be superior to penicillin at eradicating group A beta-hemolytic Streptococcus 2.
2. Clindamycin
- Dosage: 7 mg/kg three times daily (maximum 300 mg per dose) for 10 days 1
- Particularly effective for patients with recurrent strep throat or penicillin failure
- Reserved for penicillin-allergic patients or when other antibiotics are inappropriate 4
3. Macrolides
- Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days 1
- Effective for eradication of susceptible strains of Streptococcus pyogenes 5
- Important note: Some strains are resistant to azithromycin, so susceptibility testing should be performed when possible 5
Duration of Treatment
- Standard duration for most antibiotics is 10 days to prevent acute rheumatic fever 1
- Azithromycin is typically given for 5 days due to its longer half-life 1
- Some evidence suggests that shortened 5-7 day courses of antibiotics may be as effective as the traditional 10-day course for certain antibiotics 6, but this approach should be used with caution
Special Considerations
For Penicillin-Allergic Patients:
- Non-anaphylactic allergy: Consider cephalosporins (if no history of anaphylaxis to penicillin)
- Severe penicillin allergy: Use clindamycin or macrolides 1
Monitoring Response:
- Clinical improvement should occur within 24-48 hours of starting the new antibiotic
- Patients are considered non-contagious after 24 hours of effective antibiotic therapy 1
- Follow-up testing is not routinely recommended for asymptomatic patients after completing treatment 1
Recurrent Strep Throat
For patients who experience recurrence shortly after treatment completion:
- Consider retreatment with the same antibiotic used initially
- Alternative: Intramuscular benzathine penicillin G for improved compliance 1
- For multiple recurrences, consider investigation for chronic carriers in the household
Caution
- Avoid tetracyclines in children under 8 years of age 3
- Azithromycin resistance is increasingly common, so it should not be used as first-line therapy 7
- Corticosteroids are not routinely recommended but may be considered in adult patients with severe presentations in conjunction with antibiotic therapy 1
By following this approach to alternative antibiotic selection, most cases of strep throat that fail to respond to amoxicillin can be effectively treated, reducing the risk of complications such as rheumatic fever.