Can a patient with a hypersensitivity to Penicillin receive Ceftriaxone (a cephalosporin antibiotic)?

From the Guidelines

Patients with a penicillin allergy can often receive ceftriaxone, but caution is warranted, especially for those with severe penicillin allergies, as there is a risk of cross-reactivity, and alternative antibiotics may be safer options, as noted in the 2015 guidelines 1. For patients with mild penicillin allergies, such as a rash, ceftriaxone is generally safe to administer. However, for those with severe penicillin allergies, including anaphylaxis, angioedema, or severe skin reactions like Stevens-Johnson syndrome, there is approximately a 1-3% risk of cross-reactivity with cephalosporins like ceftriaxone, as mentioned in the guidelines 1. In these cases, careful risk assessment is needed, and if ceftriaxone is deemed necessary despite a severe penicillin allergy, consider skin testing first or administering the first dose under medical supervision where anaphylaxis can be treated. Some key points to consider when deciding whether to administer ceftriaxone to a patient with a penicillin allergy include:

• The severity of the penicillin allergy: patients with severe allergies, such as anaphylaxis, are at higher risk of cross-reactivity with ceftriaxone.
• The type of infection being treated: alternative antibiotics from different classes, such as fluoroquinolones, macrolides, or tetracyclines, may be safer options for patients with severe penicillin allergies, depending on the infection being treated, as suggested in the guidelines 1.
• The availability of alternative antibiotics: in some cases, alternative antibiotics may be preferred over ceftriaxone for patients with penicillin allergies, as noted in the guidelines 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 Key Considerations:

• The patient's allergy to penicillin may increase the risk of hypersensitivity to ceftriaxone.
• Ceftriaxone is contraindicated in patients with known hypersensitivity to ceftriaxone or any other cephalosporin. Answer: A patient who is allergic to penicillin may be at greater risk of hypersensitivity to ceftriaxone, but the FDA drug label does not provide a direct answer to whether they can receive ceftriaxone. However, due to the potential increased risk, it is recommended to exercise caution. 2

From the Research

Ceftriaxone Administration in Penicillin-Allergic Patients

• Ceftriaxone is a third-generation cephalosporin, and its use in penicillin-allergic patients has been studied in several research papers 3, 4.
• According to a study published in The Journal of family practice, ceftriaxone does not increase the risk of an allergic reaction in patients with penicillin allergy 3.
• Another study published in The Journal of emergency medicine found that the overall cross-reactivity rate between penicillins and cephalosporins is lower than previously reported, and the use of third- or fourth-generation cephalosporins, such as ceftriaxone, carries a negligible risk of cross-allergy 4.
• A review of penicillin allergy management published in JAMA noted that cross-reactivity between penicillin and cephalosporin drugs occurs in about 2% of cases, which is less than the previously reported 8% 5.
• A study published in Allergy and asthma proceedings also mentioned that patients with an unconfirmed penicillin allergy have a low risk of reacting to cephalosporins, including ceftriaxone 6.

Key Considerations

• The risk of cross-reactivity between penicillin and ceftriaxone is considered low, but it is essential to evaluate each patient's individual risk factors and medical history 5, 4.
• Patients with a history of penicillin allergy should be assessed for their risk of cross-reactivity with cephalosporins, and ceftriaxone can be considered a safe option for those with a low risk of cross-reactivity 3, 4.
• Penicillin skin testing and graded challenge can be used to evaluate patients with a history of penicillin allergy, and desensitization may be considered in some cases where treatment with penicillins is essential 7.