What is the best antibiotic for streptococcal pharyngitis (strep throat) in patients with a penicillin allergy?

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Last updated: July 8, 2025View editorial policy

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From the Guidelines

For patients with a penicillin allergy who have streptococcal pharyngitis (strep throat), the best antibiotic alternative is typically a first-generation cephalosporin such as cephalexin (20 mg/kg/dose twice daily, max = 500 mg/dose, for 10 days) if the allergy is non-severe, or macrolides such as azithromycin (12 mg/kg once daily, max = 500 mg, for 5 days) or clarithromycin (7.5 mg/kg/dose twice daily, max = 250 mg/dose, for 10 days) if there is a history of severe or immediate penicillin allergy, as recommended by the Infectious Diseases Society of America in 2012 1. The choice of antibiotic should consider the severity of the penicillin allergy, local resistance patterns, and patient-specific factors.

  • Cephalexin is a suitable option for patients with non-severe penicillin allergies, with a strong, high recommendation from the Infectious Diseases Society of America 1.
  • Macrolides, such as azithromycin and clarithromycin, are effective alternatives for patients with severe penicillin allergies, with a strong, moderate recommendation from the Infectious Diseases Society of America 1.
  • Clindamycin (7 mg/kg/dose 3 times daily, max = 300 mg/dose, for 10 days) is another effective option for those with severe penicillin allergies, with a strong, moderate recommendation from the Infectious Diseases Society of America 1. It's essential to note that about 10% of patients with penicillin allergies may also react to cephalosporins due to cross-reactivity, so caution is needed when using cephalosporins in these patients. The Infectious Diseases Society of America recommends avoiding cephalosporins in individuals with immediate-type hypersensitivity to penicillin 1. These alternatives work by different mechanisms to inhibit bacterial growth or kill the Streptococcus pyogenes bacteria that cause strep throat, though they may have slightly lower efficacy rates compared to penicillin, which remains the gold standard for non-allergic patients. The most recent and highest quality study, published in 2012 by the Infectious Diseases Society of America, provides the basis for these recommendations 1.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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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