What is the next step in treatment for a patient with streptococcal (strep) infection who has failed treatment with amoxicillin (amoxycillin)?

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Last updated: March 24, 2025View editorial policy

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From the Guidelines

If amoxicillin treatment for strep throat has failed, the next step is to consider alternative antibiotics such as clindamycin, azithromycin, or cephalosporins, as recommended by the Infectious Diseases Society of America 1. The most common second-line treatment is typically a 10-day course of either penicillin-resistant antibiotics like clindamycin (20-30 mg/kg/d in 3 doses) or azithromycin (12 mg/kg once daily) 1. Some key points to consider in the management of strep throat include:

  • Completing the full course of any prescribed antibiotic even if symptoms improve
  • Managing symptoms with over-the-counter pain relievers like acetaminophen or ibuprofen, warm salt water gargles, and plenty of fluids
  • Recognizing that untreated strep infections can lead to serious complications including rheumatic fever or kidney inflammation, so prompt medical attention is essential
  • Considering the potential for treatment failure due to poor medication adherence, bacterial resistance, or because the patient is a strep carrier with a concurrent viral infection It's also important to note that the choice of antibiotic should be based on the patient's medical history, including any allergies or previous reactions to antibiotics, as well as the severity of the infection and the potential for complications. In general, the goal of treatment is to eradicate the streptococcal infection, prevent complications, and improve symptoms, while also considering the potential risks and benefits of different antibiotic regimens, as outlined in the guidelines from the American Heart Association and the Infectious Diseases Society of America 1.

From the Research

Treatment Options for Streptococcal Infection

  • The patient has failed treatment with amoxicillin, and alternative antibiotics should be considered 2.
  • Cephalosporins, amoxicillin/clavulanate, and extended-spectrum macrolides are logical options for treatment 2.
  • A study comparing different antibiotics found that cephalosporins may be more effective than penicillin in symptom resolution, but the evidence is uncertain 3, 4.
  • Macrolides may have a similar effect to penicillin in resolving symptoms, but the evidence is also uncertain 3, 4.
  • Azithromycin may be an option, but the evidence is very low-certainty, and it may have more adverse events compared to amoxicillin 3, 4.
  • Carbacephem may provide better symptom resolution post-treatment compared to penicillin, but the evidence is low-certainty 3, 4.

Considerations for Treatment

  • The primary cause of penicillin treatment failure may be lack of compliance with the 10-day therapeutic regimen 5.
  • Other causes of treatment failure include reexposure to Streptococcus-infected family members or peers, copathogenicity, antibiotic-associated eradication of normal protective pharyngeal flora, and penicillin tolerance 5.
  • Short-course antimicrobial therapy may be effective in treating group A streptococcal tonsillopharyngitis 6.
  • The choice of antibiotic should be based on the patient's specific situation, and the potential benefits and risks of each option should be considered 3, 4.

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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