Is a skin test necessary before administering ceftriaxone (a cephalosporin antibiotic) to patients with a history of allergic reactions to penicillins or other beta-lactam antibiotics?

From the Guidelines

Skin testing is not routinely necessary before administering ceftriaxone to patients with a history of penicillin allergy. For most patients with reported penicillin allergies, ceftriaxone can be safely administered without prior skin testing, as the cross-reactivity risk is low, approximately 2-3% for patients with severe, immediate-type allergic reactions to penicillins 1.

Key Considerations

• Patients with a history of severe, immediate-type allergic reactions to penicillins (such as anaphylaxis, angioedema, or urticaria occurring within 1 hour of administration) may require caution and consideration of alternative antibiotics or consultation with an allergist 1.
• The risk of cross-reactivity is even lower for patients with mild, non-immediate reactions to penicillins (such as delayed rashes) 1.
• Ceftriaxone has different side chains than penicillins, reducing the likelihood of cross-reactivity, as most allergic reactions are directed at the side chains rather than the core beta-lactam structure 1.

Administration Guidance

• If ceftriaxone must be used in a patient with severe penicillin allergy, consider administering the first dose in a monitored setting where emergency treatment for anaphylaxis is readily available 1.
• For patients with a history of penicillin allergy who have negative penicillin skin test responses, cephalosporins like ceftriaxone might be safely received 1.

Evidence Basis

The recommendation against routine skin testing before administering ceftriaxone to patients with a history of penicillin allergy is based on the most recent and highest quality studies available, including the 2022 practice parameter update on drug allergy 1, which highlights the low cross-reactivity risk between penicillins and cephalosporins, especially for ceftriaxone.

From the FDA Drug Label

Before therapy with ceftriaxone for injection is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins and other beta-lactam agents or other drugs. This product should be given cautiously to penicillin and other beta-lactam agent-sensitive patients Patients with previous hypersensitivity reactions to penicillin and other beta lactam antibacterial agents may be at greater risk of hypersensitivity to ceftriaxone

Skin Test Necessity:

• The FDA drug label does not explicitly state that a skin test is necessary before administering ceftriaxone to patients with a history of allergic reactions to penicillins or other beta-lactam antibiotics.
• However, it does recommend careful inquiry and caution when administering the drug to patients with a history of hypersensitivity reactions to cephalosporins, penicillins, and other beta-lactam agents.
• Key Considerations:
  • Patients with previous hypersensitivity reactions to penicillin and other beta-lactam antibacterial agents may be at greater risk of hypersensitivity to ceftriaxone.
  • The drug should be given cautiously to penicillin and other beta-lactam agent-sensitive patients.
• Clinical Decision:
  • A conservative approach would be to exercise caution when administering ceftriaxone to patients with a history of allergic reactions to penicillins or other beta-lactam antibiotics.
  • However, the decision to perform a skin test should be made on a case-by-case basis, taking into account the patient's medical history and the potential risks and benefits of the drug 2, 2, 2.

From the Research

Skin Testing for Ceftriaxone Administration

• The decision to perform a skin test before administering ceftriaxone to patients with a history of allergic reactions to penicillins or other beta-lactam antibiotics depends on several factors.
• According to 3, patients with a history of penicillin allergy should be evaluated when they are well and not in immediate need of antibiotic therapy, and penicillin skin test-negative patients may be safely treated with all beta-lactam antibiotics.
• However, the extent of allergic cross-reactivity between penicillin and cephalosporins/carbapenems is uncertain, and penicillin skin test-positive patients should only receive these antibiotics via cautious graded challenge or desensitization 3.

Diagnostic Skin Testing

• Validated diagnostic skin testing to detect the presence of drug-specific IgE antibodies is available for penicillin, but for non-penicillin beta-lactams, the immunogenic determinants that are produced by degradation are unknown, and diagnostic skin testing is of more limited value 3.
• Penicillin skin testing can help detect patients at risk of developing an immediate allergic reaction to penicillin, and those patients with a negative test may be able to use a penicillin antibiotic safely 4.
• Cephalosporin skin testing should be restricted to research settings, as it is rarely needed clinically to safely manage patients and has unclear predictive value at this time 5.

Desensitization Procedures

• Oral desensitization is an effective, relatively safe approach to administering beta-lactam antibiotics to penicillin-allergic patients with life-threatening infections 6.
• Rapid intravenous desensitization is a rapid, safe, and effective technique for patients demonstrating hypersensitivity to beta-lactam antibiotics who require therapy with these medications 7.
• Desensitization procedures can be used to safely administer ceftriaxone to patients with a history of allergic reactions to penicillins or other beta-lactam antibiotics, but should be performed with caution and under close monitoring.