How to treat streptococcal A pharyngitis in a patient on Amoxicillin (amoxicillin) who is resistant to Ampicillin (ampicillin)?

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Last updated: April 14, 2025View editorial policy

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From the Guidelines

For strep A pharyngitis that is resistant to ampicillin but the patient is currently on amoxicillin, you should switch to an alternative antibiotic, such as cephalexin, due to the high risk of treatment failure and complications like rheumatic fever, as recommended by the most recent guidelines 1.

Recommended Treatment Options

  • Cephalexin (500 mg twice daily for 10 days) is a recommended alternative antibiotic for patients without penicillin allergy, as it has a lower rate of relapse and good tolerability 1.
  • For patients with penicillin allergy, macrolides like azithromycin (500 mg once daily for 5 days) or clindamycin (300 mg three times daily for 10 days) are appropriate alternatives, although resistance rates should be considered 1.

Rationale for Switching Antibiotics

  • Amoxicillin and ampicillin share the same mechanism of action as they are both aminopenicillins, so resistance to ampicillin typically means resistance to amoxicillin as well 1.
  • The resistance occurs when bacteria produce beta-lactamase enzymes that break down the beta-lactam ring in these antibiotics, rendering them ineffective 1.

Importance of Complete Treatment

  • Complete treatment is crucial to prevent complications like rheumatic fever and to ensure eradication of the bacteria from the pharynx 1.
  • Inappropriate antimicrobial use for upper respiratory tract infections, including acute pharyngitis, has been a major contributor to the development of antimicrobial resistance among common pathogens 1.

From the FDA Drug Label

Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy NOTE: Penicillin by the intramuscular route is the usual drug of choice in the treatment of Streptococcus pyogenes infection and the prophylaxis of rheumatic fever. Azithromycin is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx Because some strains are resistant to azithromycin, susceptibility tests should be performed when patients are treated with azithromycin.

The patient is on amoxicillin but the bacteria is resistant to ampicillin, azithromycin can be used as an alternative therapy for strep A pharyngitis in individuals who cannot use first-line therapy, such as those with resistance to ampicillin 2 2. Susceptibility tests should be performed to ensure the bacteria is susceptible to azithromycin. Key considerations include:

  • Azithromycin is often effective in eradicating susceptible strains of Streptococcus pyogenes
  • Penicillin is the usual drug of choice, but azithromycin can be used as an alternative
  • Susceptibility tests are necessary to ensure the bacteria is susceptible to azithromycin

From the Research

Treatment of Strep A Pharyngitis

If a patient is on amoxicillin but resistant to ampicillin, the following options can be considered:

  • Cephalosporins: There is low-certainty evidence that cephalosporins may be as effective as penicillin in treating GABHS tonsillopharyngitis 3, 4.
  • Macrolides: The evidence is uncertain regarding the effectiveness of macrolides compared to penicillin in treating GABHS tonsillopharyngitis 3, 4.
  • Carbacephem: There is low-certainty evidence that carbacephem may provide better symptom resolution post-treatment in adults and children compared to penicillin 3, 4.
  • Azithromycin: One unpublished trial in children found that azithromycin in a single dose may be as effective as amoxicillin for 10 days in treating GABHS tonsillopharyngitis, but the evidence is very low-certainty 3, 4.

Key Points

  • The effectiveness of antibiotics in treating GABHS pharyngitis is modest, and the choice of antibiotic should be based on individual patient factors and resistance patterns 3, 4, 5.
  • Penicillin can be used as a first-line treatment for GABHS pharyngitis if an antibiotic is indicated 4, 5.
  • There is a need for trials in low-income countries and disadvantaged populations to determine the best approach to diagnosis and treatment of GABHS pharyngitis 3, 4.

Considerations

  • The treatment of GABHS pharyngitis should be guided by clinical judgment and individual patient factors, including antibiotic resistance patterns and potential allergies 5.
  • The use of antibiotics should be balanced with the risk of adverse effects and the potential for antimicrobial resistance 3, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Different antibiotic treatments for group A streptococcal pharyngitis.

The Cochrane database of systematic reviews, 2021

Research

Different antibiotic treatments for group A streptococcal pharyngitis.

The Cochrane database of systematic reviews, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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