What is the treatment for streptococcal pharyngitis in a patient with a penicillin (PCN) allergy and an allergy to azithromycin (Zithromax, Z-Pak)?

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From the Guidelines

For patients allergic to both penicillin (PCN) and azithromycin (Z-Pak), clindamycin is the recommended treatment for strep throat, as stated in the 2012 update by the Infectious Diseases Society of America 1. The typical adult dosage is clindamycin 300 mg orally three times daily for 10 days, and for children, the dosage is 7 mg/kg/dose three times daily (max = 300 mg/dose) for 10 days, as outlined in the guideline 1. Alternative options include first-generation cephalosporins like cephalexin (20 mg/kg/dose twice daily, max = 500 mg/dose) for 10 days, if the penicillin allergy is not severe or anaphylactic, considering the approximately 10% cross-reactivity between penicillins and cephalosporins 1. It's crucial to complete the full course of antibiotics even if symptoms improve before finishing the medication. Patients should also take measures to relieve symptoms, including:

  • Adequate hydration
  • Rest
  • Over-the-counter pain relievers like acetaminophen or ibuprofen for fever and throat pain
  • Warm salt water gargles Strep throat requires antibiotic treatment to prevent complications such as rheumatic fever and kidney inflammation, so proper treatment despite allergies is essential, as emphasized in the clinical practice guideline 1. If symptoms worsen or don't improve within 48 hours of starting antibiotics, medical reevaluation is necessary.

From the Research

Treatment Options for Strep Throat

If a patient is allergic to PCN (penicillin) and Z-Pak (azithromycin), there are alternative treatment options available for strep throat.

  • First-generation cephalosporins can be used as a substitute for penicillin in patients with non-anaphylactic allergies to penicillin 2, 3.
  • Clindamycin is another option for patients allergic to penicillin 2.
  • Macrolide antibiotics, such as erythromycin or clarithromycin, can also be used, but there is significant resistance to these antibiotics in some parts of the United States 3.

Considerations for Antibiotic Selection

When selecting an antibiotic for a patient with a penicillin allergy, it is essential to consider the type of allergic reaction the patient has experienced.

  • Patients with unknown or possible reactions to penicillin, or those with a drug fever or rash, may be able to tolerate beta-lactam antibiotics 4.
  • However, patients with hives or anaphylactic reactions should not be given penicillins or beta-lactams, and alternative antibiotics that do not cross-react with penicillins or beta-lactams should be used instead 4.

Efficacy of Alternative Antibiotics

Research has shown that alternative antibiotics, such as cephalosporins and macrolides, may be effective in treating strep throat, although the evidence is not always conclusive.

  • Cephalosporins may be more effective than penicillin in preventing clinical relapse, especially in adults 5, 6.
  • Carbacephem may provide better symptom resolution post-treatment in adults and children compared to penicillin 6.
  • However, the evidence is generally of low certainty, and more research is needed to determine the most effective antibiotic treatments for strep throat in patients with penicillin allergies 5, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Common Questions About Streptococcal Pharyngitis.

American family physician, 2016

Research

Streptococcal Pharyngitis: Rapid Evidence Review.

American family physician, 2024

Research

Antibiotic selection in the penicillin-allergic patient.

The Medical clinics of North America, 2006

Research

Different antibiotic treatments for group A streptococcal pharyngitis.

The Cochrane database of systematic reviews, 2013

Research

Different antibiotic treatments for group A streptococcal pharyngitis.

The Cochrane database of systematic reviews, 2021

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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