What are the considerations for administering cephalosporins (a type of antibiotic) to patients with a history of Immunoglobulin E (IgE)-mediated allergic reactions to cephalosporins or penicillins?

From the Guidelines

Patients with a history of IgE-mediated allergic reactions to cephalosporins or penicillins should generally avoid receiving the same or structurally similar cephalosporins due to the risk of cross-reactivity. For patients with confirmed cephalosporin allergy, alternative antibiotic classes should be used when possible. If a cephalosporin is absolutely necessary, skin testing should be performed first to assess risk, followed by graded challenge or desensitization protocols under close medical supervision, as recommended by the most recent practice parameter update 1. The cross-reactivity between penicillins and cephalosporins is primarily related to their beta-lactam ring structure, with first-generation cephalosporins having approximately 10% cross-reactivity with penicillins, while later generations (third and fourth) have much lower rates (less than 2%) 1. Some key points to consider when evaluating a patient's allergy history include:

• Distinguishing between true IgE-mediated reactions (hives, anaphylaxis, angioedema) and non-immunologic adverse effects (gastrointestinal upset, non-specific rash) 1
• The use of aztreonam, which has no cross-reactivity with penicillin and most cephalosporins, except for ceftazidime, which shares a common R-group side chain 1
• The importance of skin testing and graded challenge or desensitization protocols in patients with a history of penicillin or cephalosporin allergy who require cephalosporin treatment 1 For patients requiring cephalosporins despite allergies, administration should occur in a controlled setting with emergency medications readily available, including epinephrine, antihistamines, and corticosteroids, as the benefit of administering the cephalosporin must clearly outweigh the risk of a potentially severe allergic reaction 1.

From the FDA Drug Label

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefepime Injection and other antibacterial drugs, Cefepime Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. WARNINGS AND PRECAUTIONS • Cross-hypersensitivity among beta-lactam antibacterial drugs may occur in up to 10% of patients with a history of penicillin allergy. CONTRAINDICATIONS • Prior immediate hypersensitivity reactions to cefepime or the cephalosporin class of antibacterial drugs, penicillins, and other beta-lactam antibacterial drugs

IgE-mediated allergic reactions to cephalosporins, including cefepime, can occur.

• Key considerations for administering cephalosporins to patients with a history of IgE-mediated allergic reactions to cephalosporins or penicillins include:
  • Assessing the patient's allergy history and the severity of previous reactions
  • Considering alternative antibiotic options
  • Monitoring the patient closely for signs of an allergic reaction if cefepime is administered 2
  • Being aware of the potential for cross-hypersensitivity among beta-lactam antibacterial drugs, which may occur in up to 10% of patients with a history of penicillin allergy 2 Cefepime is contraindicated in patients who have shown immediate hypersensitivity reactions to cefepime or the cephalosporin class of antibacterials, penicillins or other beta-lactam antibacterial drugs 2

From the Research

Considerations for Administering Cephalosporins

• Patients with a history of IgE-mediated allergic reactions to cephalosporins or penicillins require careful consideration before administering cephalosporins 3, 4, 5, 6, 7.
• The risk of 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 5.
• The use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin carries a negligible risk of cross allergy 5, 7.
• Skin testing to the cephalosporin in question, using a nonirritating concentration, provides additional information to guide the work-up of a patient suspected of having an allergy to that drug 6.
• Patients with an IgE-mediated hypersensitivity to penicillins could be treated with cephalosporins such as cefuroxime and ceftriaxone that have side-chain determinants different from those of penicillins and are negative in pretreatment skin testing 7.

Cross-Reactivity Patterns

• Cross-reactivity between penicillins and cephalosporins seems to be mainly related to side chain similarity or identity 5, 7.
• Patients with a history of penicillin allergy are at increased risk of adverse drug reactions when administered cephalosporin, especially first-generation cephalosporins 4.
• Co-sensitisation to other cephalosporins or penicillins is uncommon, and when it occurs, is usually consistent with side chain cross-reactivity 3.

Diagnostic Approaches

• Specific IgE testing to penicillin, amoxycillin, and cefaclor, followed by skin prick testing, intradermal testing, and drug provocation testing with a panel of penicillins and cephalosporins can help define cross-reactivity patterns in patients with confirmed allergy to a cephalosporin 3.
• Serum specific IgE assays for cefaclor, as well as skin tests with various cephalosporins, can be used to assess cross-reactivity with cephalosporins in patients with IgE-mediated hypersensitivity to penicillins 7.