What antibiotics (abx) can be used to treat streptococcal (strep) infections in patients with a penicillin (pcn) allergy?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: March 27, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

For strep throat in patients allergic to penicillin, macrolides like azithromycin (500 mg on day 1, then 250 mg daily for 4 days) or clarithromycin (250 mg twice daily for 10 days) are good first-line alternatives, as recommended by the most recent study 1. When considering treatment options for streptococcal infections in patients with a penicillin allergy, it's essential to prioritize alternatives that are effective, safe, and have a low risk of cross-reactivity.

  • Macrolides, such as azithromycin and clarithromycin, are suitable choices, as they have been shown to be effective in treating group A streptococcal pharyngitis 1.
  • Clindamycin (300 mg three times daily for 10 days) is also an effective option for more severe cases or when macrolides are not suitable, as noted in earlier studies 1.
  • Cephalosporins, like cefuroxime (250 mg twice daily for 10 days), may be used in patients with non-anaphylactic penicillin allergies, as the cross-reactivity is relatively low (around 5-10%) 1. However, it's crucial to avoid cephalosporins in patients with severe penicillin allergies due to the potential for cross-reactivity. The most recent study 1 supports the use of macrolides as a first-line alternative, and it's essential to complete the full course of antibiotics to prevent complications like rheumatic fever. If you have a history of severe allergic reactions to penicillin, it's vital to inform all healthcare providers and consider wearing a medical alert bracelet.

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

Azithromycin can be used to treat streptococcal infections in patients with a penicillin allergy, as an alternative to first-line therapy.

  • Key points:
    • Azithromycin is effective in eradicating susceptible strains of Streptococcus pyogenes from the nasopharynx.
    • Susceptibility tests should be performed when patients are treated with azithromycin, as some strains may be resistant.
    • Data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available 2 2.

From the Research

Alternatives to Penicillin for Treating Streptococcal Infections

In patients with a penicillin allergy, alternative antibiotics can be used to treat streptococcal infections. The following options are available:

  • Macrolides, such as clarithromycin and azithromycin, which offer lower rates of gastrointestinal complaints and more convenient dosing compared to erythromycin 3
  • Cephalosporins, which have a low cross-reactivity with penicillins, estimated at 2-3% among patients with a verified penicillin allergy 4
  • Other antibiotics that do not cross-react with penicillins or beta-lactams, which can be used safely in patients with a penicillin allergy 5

Specific Antibiotics for Streptococcal Pharyngitis

For the treatment of streptococcal pharyngitis, the following antibiotics can be used:

  • Clarithromycin, which has been shown to be as safe and effective as penicillin VK in the treatment of streptococcal pharyngitis 6
  • Azithromycin, which offers a convenient once-daily dosing regimen and a shorter treatment duration of 5 days compared to penicillin, erythromycin, and clarithromycin 3

Management of Penicillin Allergy

In patients with a penicillin allergy, skin tests can be used to exclude the risk of IgE-mediated reactions to subsequent penicillin administration 7. If penicillin is the first choice for treatment and the patient has an IgE-mediated allergy, desensitization therapy to the drug can be performed 7. Allergy evaluation using a detailed patient history and allergy testing (skin testing and/or oral challenge) when indicated has been shown to be safe and effective and is an important part of antibiotic stewardship 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Macrolides in the management of streptococcal pharyngitis/tonsillitis.

The Pediatric infectious disease journal, 1997

Research

Antibiotic selection in the penicillin-allergic patient.

The Medical clinics of North America, 2006

Research

Clarithromycin versus penicillin in the treatment of streptococcal pharyngitis.

The Journal of antimicrobial chemotherapy, 1991

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.