Is cefazolin safe to use in patients with a penicillin 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: February 22, 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

Cefazolin can be safely used in patients with a penicillin allergy, with a cross-reactivity rate of 0.7% (95% CrI: 0.1%-1.7%) as reported in the most recent study 1. When considering the use of cefazolin in patients with a penicillin allergy, it is essential to weigh the benefits and risks. The risk of cross-reactivity between penicillins and cephalosporins, such as cefazolin, is lower than previously thought. According to the latest evidence 1, the cross-reactivity rate among patients with an unverified penicillin allergy is 0.7%, and 0.8% among those with a confirmed penicillin allergy.

Key Considerations

  • The chemical structure of cefazolin is similar to that of penicillins, which may lead to cross-reactivity in some patients 1.
  • However, the actual risk of cross-reactivity is relatively low, and cefazolin can be used in patients with a penicillin allergy under close medical supervision.
  • Alternative antibiotics or allergy testing may be considered in some cases, especially if the penicillin allergy is severe or the patient has a history of anaphylaxis 1, 1.

Recommendations

  • Cefazolin can be used in patients with a penicillin allergy, but with caution and close monitoring 1.
  • Patients with a history of anaphylaxis or severe reactions to penicillins should be treated with alternative antibiotics, such as ciprofloxacin plus clindamycin or aztreonam plus vancomycin 1.
  • Allergy evaluation for tolerance to β-lactam therapy should be done in every case in which vancomycin is considered for use 1.

From the FDA Drug Label

WARNINGS BEFORE THERAPY WITH CEFAZOLIN IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFAZOLIN, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS IF THIS PRODUCT IS GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. CONTRAINDICATIONS CEFAZOLIN IS CONTRAINDICATED IN PATIENTS WITH KNOWN ALLERGY TO THE CEPHALOSPORIN GROUP OF ANTIBIOTICS.

Cefazolin is not absolutely safe to use in patients with a penicillin allergy due to the potential for cross-hypersensitivity among beta-lactam antibiotics, which may occur in up to 10% of patients with a history of penicillin allergy 2. However, it is not contraindicated in patients with a penicillin allergy, but rather in patients with a known allergy to the cephalosporin group of antibiotics 2. Caution should be exercised when administering cefazolin to penicillin-sensitive patients.

From the Research

Safety of Cefazolin in Patients with Penicillin Allergy

  • Cefazolin is considered safe to use in patients with a penicillin allergy, with a low risk of cross-reactivity between the two antibiotics 3, 4, 5, 6.
  • The risk of allergic reaction to cefazolin in patients with a penicillin allergy is estimated to be less than 1% 6.
  • Studies have shown that cefazolin can be prescribed safely for penicillin-allergic patients, with no increased risk of severe allergic reactions 7, 5.

Conditions for Safe Use

  • Cefazolin should only be avoided in patients with a history of severe, life-threatening delayed hypersensitivity reaction to penicillin, such as Steven-Johnson Syndrome, hepatitis, nephritis, serum sickness, and hemolytic anemia 3.
  • Patients with a confirmed penicillin allergy may require additional care and evaluation before receiving cefazolin 6.

Benefits of Using Cefazolin

  • Cefazolin is the most common first-line antibiotic for surgical prophylaxis and is associated with lower rates of surgical-site infections and multi-drug resistant infections compared to alternative antibiotics 7.
  • Using cefazolin as the first-line antibiotic can reduce the risk of antimicrobial resistance and adverse events 4.

Evaluation and Management of Penicillin Allergy

  • Evaluation of penicillin allergy is important to determine the safety of using cefazolin and other beta-lactam antibiotics 4.
  • Penicillin skin testing and amoxicillin challenge can be used to evaluate patients with a reported penicillin allergy 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.

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.