Is ceftriaxone (a cephalosporin antibiotic) safe to use in patients with a penicillin allergy?

From the Guidelines

Ceftriaxone can be used in many patients with penicillin allergy, but caution is needed, especially in those with severe penicillin allergies, where cross-reactivity is approximately 1-3%. For patients with mild penicillin allergies (like rash), ceftriaxone is generally safe to use 1. However, for patients with severe penicillin allergies (anaphylaxis, angioedema, or severe skin reactions like Stevens-Johnson syndrome), skin testing or graded challenge might be considered, or alternative antibiotics should be used 1. The cross-reactivity occurs because both penicillins and cephalosporins share a beta-lactam ring structure, though newer generation cephalosporins like ceftriaxone (third-generation) have less cross-reactivity than first-generation cephalosporins. Some key points to consider when using ceftriaxone in patients with penicillin allergy include:

• The typical adult dose of ceftriaxone is 1-2 grams IV/IM daily or divided twice daily, depending on the infection being treated.
• Always document the nature of the penicillin allergy in the patient's chart and monitor closely when administering ceftriaxone to patients with penicillin allergy.
• A study of 417 patients across 12 clinical studies conducted after 1980 found that 8 (2%) had reactions to cephalosporins, representing cross-reactivity ranging between 2.0% and 4.8% 1.
• Another study found that the reaction rate among patients with a confirmed penicillin allergy was recently determined to be just 0.8% (95% CI: 0.13%-4.1%) among 131 patients who are confirmed to be penicillin-allergic 1. It is essential to weigh the benefits and risks of using ceftriaxone in patients with penicillin allergy, considering the severity of the allergy and the potential for cross-reactivity.

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 Antibacterial drugs should be administered with caution to any patient who has demonstrated some form of allergy, particularly to drugs.

Ceftriaxone Safety in Penicillin Allergy:

• Ceftriaxone may not be safe to use in patients with a penicillin allergy, as these patients may be at a greater risk of hypersensitivity reactions.
• The drug should be given cautiously to penicillin-sensitive patients.
• Patients with a history of allergy to penicillin or other beta-lactam agents should be monitored closely for signs of hypersensitivity reactions when treated with ceftriaxone 222.

From the Research

Ceftriaxone Safety in Patients with Penicillin Allergy

• Ceftriaxone, a cephalosporin antibiotic, can be safely used in patients with a penicillin allergy, as the cross-reactivity between penicillins and cephalosporins is extremely low, estimated at 2% to 3% among patients with a verified penicillin allergy 3.
• Studies have shown that cephalosporins, including ceftriaxone, do not increase the risk of an allergic reaction in patients with penicillin allergy 4.
• The use of ceftriaxone in patients with penicillin allergy is supported by guidelines, which recommend the routine use of structurally dissimilar cephalosporins, such as ceftriaxone, even in patients with an anaphylactic penicillin allergy 3.
• A literature review found that the overall cross-reactivity rate between penicillins and cephalosporins is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains, and that third- or fourth-generation cephalosporins, such as ceftriaxone, carry a negligible risk of cross allergy 5.
• Another study found that ceftriaxone is one of the cephalosporins that does not increase the risk of an allergic reaction among patients with penicillin allergy 4.

Key Findings

• More than 90% of patients who report a penicillin allergy are not truly allergic and would tolerate penicillins if administered 3.
• Allergy evaluation using a detailed patient history and allergy testing (skin testing and/or oral challenge) when indicated has been shown to be safe and effective 3.
• The use of alternative antibiotics in patients with penicillin allergy can lead to increased antibiotic resistance, toxicity, and healthcare cost 3.
• Ceftriaxone can be safely used in patients with penicillin allergy, and its use is supported by guidelines and studies 3, 4, 5.