What is the risk of cross-reactivity between cefdinir (Omnicef) and penicillin in patients with a known penicillin allergy?

From the Guidelines

Patients with a penicillin allergy have a very low risk of cross-reactivity with cefdinir (Omnicef), which is a third-generation cephalosporin, with a reaction rate of approximately 0.8% (95% CI: 0.13%-4.1%) among confirmed penicillin-allergic patients 1.

Key Points to Consider

• The risk of cross-reactivity between cefdinir and penicillin is lower than with first-generation cephalosporins, due to differences in side chains in third-generation cephalosporins like cefdinir 1.
• For patients with a history of mild penicillin allergy (such as rash), cefdinir can generally be used with caution, while for patients with a history of severe penicillin allergy (anaphylaxis, angioedema, or Stevens-Johnson syndrome), it's recommended to avoid cefdinir or administer it under medical supervision with emergency measures available.
• The cross-reactivity occurs because both penicillins and cephalosporins share a beta-lactam ring structure, though differences in side chains in third-generation cephalosporins like cefdinir reduce the likelihood of allergic response 1.

Important Considerations for Clinical Practice

• When treating patients with penicillin allergies, it's essential to document the nature and severity of the previous reaction to make an informed risk assessment before prescribing cefdinir 1.
• Skin testing is not recommended for routine use but may be advisable for specific patients with multiple drug allergies because of the possibility of coexisting sensitivities 1.
• The reaction rate among patients with a confirmed penicillin allergy was recently determined to be just 0.8% (95% CI: 0.13%-4.1%) among 131 patients who are confirmed to be penicillin-allergic, indicating a low risk of cross-reactivity with cefdinir 1.

From the FDA Drug Label

WARNINGS BEFORE THERAPY WITH CEFDINIR IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFDINIR, OTHER CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS IF CEFDINIR IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG β-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. The risk of cross-reactivity between cefdinir and penicillin in patients with a known penicillin allergy is estimated to occur in up to 10% of patients, as cross-hypersensitivity among β-lactam antibiotics has been clearly documented 2.

• Key points:
  • Cefdinir should be given with caution to penicillin-sensitive patients.
  • Cross-hypersensitivity may occur in up to 10% of patients with a history of penicillin allergy.
  • If an allergic reaction to cefdinir occurs, the drug should be discontinued.

From the Research

Cefdinir Penicillin Cross Reactivity

• The risk of cross-reactivity between cefdinir (Omnicef) and penicillin in patients with a known penicillin allergy is a concern for clinicians 3, 4, 5, 6, 7.
• Studies have shown that the overall cross-reactivity rate between penicillins and cephalosporins is lower than previously reported, with an estimated rate of approximately 1% to 2% 3, 4.
• The cross-reactivity between penicillins and cephalosporins is attributed to the R1 side chain, with first-generation cephalosporins having a higher cross-reactivity rate than second-generation cephalosporins 4.
• Cefdinir, a third-generation cephalosporin, is expected to have a negligible risk of cross-allergy with penicillins, especially if the patient's penicillin allergy is not severe 4, 6, 7.
• A study found that patients with a penicillin allergy can tolerate therapeutic doses of cephalosporins with a different side chain to the penicillin responsible for the allergic reaction, without any ill effect 7.

Risk Assessment

• Clinicians should assess the patient's allergy history and determine the severity of the penicillin allergy to estimate the risk of cross-reactivity with cefdinir 3, 5.
• Patients with a low-risk allergy history, such as isolated non-allergic symptoms or a family history of penicillin allergy, can be considered for cefdinir treatment 3.
• Patients with a moderate- to high-risk allergy history, such as anaphylaxis or positive penicillin skin testing, should be approached with caution and alternative treatments considered 3, 5.

Clinical Implications

• The use of cefdinir in patients with a known penicillin allergy should be based on a thorough evaluation of the patient's allergy history and the potential benefits and risks of treatment 3, 5, 6.
• Clinicians should be aware of the low cross-reactivity rate between penicillins and cephalosporins, such as cefdinir, and not avoid their use unnecessarily, as this can lead to the use of broad-spectrum antibiotics and increased risk of antimicrobial resistance 3, 5.