Is it safe to administer ceftriaxone (a cephalosporin antibiotic) in a patient with a penicillin allergy?

From the Guidelines

Ceftriaxone can be safely administered in patients with a penicillin allergy, except in those with a history of anaphylaxis, Stevens Johnson syndrome, or toxic epidermal necrolysis, where its use is contraindicated. When considering the administration of ceftriaxone in a patient with a penicillin allergy, it is crucial to obtain a detailed allergy history, including the specific reaction, its timing, and severity 1. The cross-reactivity between penicillins and cephalosporins, such as ceftriaxone, is estimated to be less than 5% 1, with the risk being lower for third-generation cephalosporins like ceftriaxone.

For patients with mild penicillin allergies, such as a non-urticarial rash, ceftriaxone can often be used safely 1. However, for patients with severe penicillin allergies requiring broad-spectrum coverage, alternative antibiotics like aztreonam, fluoroquinolones, or vancomycin plus an aminoglycoside may be more appropriate. If ceftriaxone is deemed necessary despite a severe penicillin allergy, consideration should be given to consulting an allergist for potential skin testing or graded challenge protocols 1. Key points to consider include:

• The severity of the penicillin allergy
• The specific reaction to penicillin
• The timing and severity of the reaction
• The potential benefits and risks of administering ceftriaxone
• The availability of alternative antibiotics.

Given the most recent and highest quality evidence, the use of ceftriaxone in patients with a penicillin allergy should be approached with caution, taking into account the individual patient's allergy history and the potential risks and benefits 1.

From the FDA Drug Label

Patients with previous hypersensitivity reactions to penicillin and other beta lactam antibacterial agents may be at greater risk of hypersensitivity to ceftriaxone This product should be given cautiously to penicillin and other beta-lactam agent-sensitive patients Serious acute hypersensitivity reactions may require the use of subcutaneous epinephrine and other emergency measures.

It is not safe to administer ceftriaxone to a patient with a penicillin allergy without caution. Hypersensitivity reactions are a concern, and the patient should be closely monitored. The drug should be given cautiously to patients with a history of hypersensitivity to penicillin or other beta-lactam agents. Key considerations include:

• Previous hypersensitivity reactions to penicillin or other beta-lactam agents
• Risk of hypersensitivity to ceftriaxone
• Need for caution when administering the drug to sensitive patients
• Potential for serious acute hypersensitivity reactions 2 2

From the Research

Cephalosporin Administration in Penicillin-Allergic Patients

• The administration of ceftriaxone, a cephalosporin antibiotic, in patients with a penicillin allergy is considered safe by some studies 3.
• Ceftriaxone is listed as one of the cephalosporins that do not increase the risk of an allergic reaction in patients with penicillin allergy 3.
• However, other studies suggest that patients with a definite history of an immediate reaction to penicillin are more likely to develop a cephalosporin reaction, including anaphylaxis 4.
• The overall cross-reactivity rate between penicillins and cephalosporins is estimated to be around 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 5.
• Third- or fourth-generation cephalosporins, such as ceftriaxone, or cephalosporins with dissimilar side chains than the offending penicillin, carry a negligible risk of cross-allergy in penicillin-allergic patients 5.

Factors Influencing Cross-Reactivity

• The presence of an amino benzyl side chain in the cephalosporin molecule may increase the risk of cross-reactivity in penicillin-allergic patients 4.
• The type of penicillin allergy reaction, such as immediate or delayed, may also influence the risk of cross-reactivity with cephalosporins 4.
• The use of second-generation cephalosporins, especially those with an amino benzyl side chain, may be associated with a higher risk of cross-reactivity in penicillin-allergic patients 4.

Clinical Implications

• Clinicians should be aware of the low cross-reactivity rate between penicillins and cephalosporins, especially with third- or fourth-generation cephalosporins 5.
• Patients with a history of penicillin allergy can be safely treated with ceftriaxone, but caution should be exercised in patients with a definite history of an immediate reaction to penicillin 4, 3.
• Electronic health care record systems should be updated to reflect the current evidence on cephalosporin use in penicillin-allergic patients, as avoiding β-lactam antibiotics can result in worse long-term global outcomes 6.