Will a patient with a history of anaphylaxis to Augmentin (amoxicillin-clavulanate) react to cefazolin?

From the Guidelines

A patient with a history of anaphylaxis to Augmentin (amoxicillin-clavulanate) should generally avoid cefazolin due to the risk of cross-reactivity between penicillins and cephalosporins, although the risk is lower than previously thought, estimated to be around 2% for first-generation cephalosporins like cefazolin 1. The cross-reactivity risk exists because both medication classes share a similar beta-lactam ring structure. However, recent studies suggest that the cross-reactivity between penicillins and cephalosporins is lower than previously estimated, with a reaction rate of 0.8% (95% CI: 0.13%-4.1%) among patients with confirmed penicillin allergy 1.

Key Considerations

• The risk of cross-reactivity is particularly concerning in patients with a history of anaphylaxis, which is a severe, potentially life-threatening allergic reaction.
• Cefazolin has a unique side chain and appears to have very low cross-reactivity with penicillins despite being a first-generation cephalosporin 1.
• For patients with a history of anaphylaxis to penicillins, alternative antibiotic classes such as macrolides, fluoroquinolones, or clindamycin should be considered depending on the infection being treated.
• If a cephalosporin is absolutely necessary, consultation with an allergist for potential skin testing or graded challenge might be appropriate, although the utility of skin testing is still debated 1.

Recommendations

• Avoid cefazolin in patients with a history of anaphylaxis to Augmentin (amoxicillin-clavulanate) unless no reasonable alternatives exist and the benefit clearly outweighs the risk.
• Consider alternative antibiotic classes such as macrolides, fluoroquinolones, or clindamycin for patients with a history of anaphylaxis to penicillins.
• Consult with an allergist for potential skin testing or graded challenge if a cephalosporin is absolutely necessary.

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.

The patient with a history of anaphylaxis to Augmentin (amoxicillin-clavulanate), which is a penicillin-based antibiotic, may be at risk of cross-hypersensitivity reaction to cefazolin, as it is a cephalosporin antibiotic, and cross-hypersensitivity among beta-lactam antibiotics has been documented.

• Key points:
  • Cefazolin is a cephalosporin antibiotic
  • Augmentin is a penicillin-based antibiotic
  • Cross-hypersensitivity among beta-lactam antibiotics may occur in up to 10% of patients with a history of penicillin allergy Given this information, caution should be exercised when administering cefazolin to a patient with a history of anaphylaxis to Augmentin 2.

From the Research

Allergic Reaction to Cefazolin

• A patient with a history of anaphylaxis to Augmentin (amoxicillin-clavulanate) may be concerned about reacting to cefazolin, a type of cephalosporin antibiotic.
• According to a study published in 2012 3, the cross-reactivity between penicillins and cephalosporins 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.
• Cefazolin is a first-generation cephalosporin, and its use in penicillin-allergic patients may confer an increased risk of allergic reaction, as reported in a study published in 2006 4.
• However, another study published in 2018 5 suggests that later-generation cephalosporins, which have distinct side chains, do not have any skin test cross-reactivity with penicillin/amoxicillin, and that the use of cephalosporins in patients with isolated confirmed penicillin or amoxicillin allergy carries a negligible risk of cross allergy.

Cross-Reactivity and Allergic Reactions

• The cross-reactivity between β-lactam antibiotics, including penicillins and cephalosporins, is mainly due to the similarity of their side-chain structures, as reported in a study published in 2021 6.
• A study published in 2012 3 found that penicillins have a cross allergy with first-generation cephalosporins, but a negligible cross allergy with second-generation cephalosporins.
• The management of anaphylaxis, a life-threatening systemic reaction, involves removal of the trigger, early administration of intramuscular epinephrine, and supportive care, as reported in a study published in 2020 7.

Cefazolin Use in Penicillin-Allergic Patients

• While there is a potential risk of cross-reactivity between penicillins and cefazolin, the overall risk is considered low, and cefazolin can be prescribed safely for penicillin-allergic patients, as reported in a study published in 2006 4.
• However, it is essential to carefully evaluate the patient's allergy history and consider alternative antibiotics if necessary, as reported in a study published in 2021 6.