Is there a contraindication to Cefazolin (Ancef) use in patients with a Cefdinir (Omnicef) allergy?

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From the Guidelines

An allergy to Omnicef (cefdinir) does not necessarily create a hard contraindication to Ancef (cefazolin), as cross-reactivity between different generations of cephalosporins is generally low, around 1-10% 1.

Key Considerations

  • Patients with a history of mild reactions to Omnicef (such as rash) may often tolerate Ancef safely, but caution is warranted, and clinical judgment is essential.
  • If the previous reaction to Omnicef was severe (anaphylaxis, Stevens-Johnson syndrome, or other life-threatening reaction), then Ancef should be avoided as the risk of cross-reactivity becomes more concerning.
  • In cases of mild previous reactions, some clinicians may choose to administer Ancef with careful monitoring, possibly starting with a test dose.

Rationale

  • The cross-reactivity occurs because cephalosporins share a similar beta-lactam ring structure, but differences in side chains between various cephalosporins affect the likelihood of cross-reactivity 1.
  • A recent study found that the reaction rate among patients with a confirmed penicillin allergy was just 0.8% (95% CI: 0.13%-4.1%) among 131 patients who are confirmed to be penicillin-allergic 1.
  • Another study found that the cross-reactivity rate to cefazolin among patients with an unverified penicillin allergy is 0.7% (95% CrI: 0.1%-1.7%) 1.

Clinical Implications

  • The decision to administer Ancef to a patient with a history of Omnicef allergy should be individualized based on the severity of the prior reaction, the necessity of the antibiotic, and available alternatives.
  • Clinicians should exercise caution and consider the potential risks and benefits of administering Ancef to a patient with a history of Omnicef allergy.
  • Further evaluation, such as skin testing, may be necessary in some cases to determine the safety of administering Ancef to a patient with a history of Omnicef allergy 1.

From the FDA Drug Label

CEFAZOLIN IS CONTRAINDICATED IN PATIENTS WITH KNOWN ALLERGY TO THE CEPHALOSPORIN GROUP OF ANTIBIOTICS. There is a contraindication to Cefazolin (Ancef) use in patients with a known allergy to the cephalosporin group of antibiotics. Since Cefdinir (Omnicef) is a cephalosporin antibiotic, patients with a Cefdinir allergy may be at risk. Therefore, Cefazolin is contraindicated in patients with a Cefdinir allergy, due to the risk of cross-reactivity within the cephalosporin group 2.

From the Research

Cephalosporin Allergy and Cross-Reactivity

  • Cephalosporins are a class of antibiotics that are commonly prescribed due to their wide clinical utility and general tolerability 3.
  • The cross-reactivity between cephalosporins and other antibiotics, such as penicillins, is a concern for clinicians when prescribing antibiotics to patients with a history of allergy 4, 5.
  • Studies have shown that the cross-reactivity between cephalosporins and penicillins is lower than previously reported, with an overall cross-reactivity rate of approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 5.

Cefazolin and Penicillin Allergy

  • Cefazolin, a first-generation cephalosporin, is often used in surgery to treat or prevent bacterial infection of the surgical site 6.
  • There is no direct evidence to suggest a contraindication to Cefazolin use in patients with a Cefdinir (Omnicef) allergy, as Cefdinir is a third-generation cephalosporin and Cefazolin is a first-generation cephalosporin.
  • However, patients with a penicillin allergy may have a higher risk of cross-reactivity with first-generation cephalosporins like Cefazolin, although the risk is still considered low 4, 5.

R1 Side Chain and Cross-Reactivity

  • The R1 side chain of cephalosporins is responsible for cross-reactivity with penicillins, and clinicians should be aware of R1 side chain similarities when prescribing alternate β-lactams in allergic individuals 3, 5.
  • Later-generation cephalosporins, which have distinct side chains, do not have any skin test cross-reactivity with penicillin/amoxicillin 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cross-reactivity in β-Lactam Allergy.

The journal of allergy and clinical immunology. In practice, 2018

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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