What is the management of a Ceftriaxone (Cephalosporin antibiotic) allergy?

From the Guidelines

For patients with a ceftriaxone allergy, management should prioritize avoiding all beta-lactam antibiotics if the patient had a severe immediate hypersensitivity reaction, and using alternative agents such as aztreonam, fluoroquinolones, or macrolides depending on the infection being treated. The approach to managing ceftriaxone allergy involves considering the severity and type of the previous reaction. According to the Dutch Working Party on Antibiotic Policy (SWAB) guideline 1, patients with a suspected immediate-type allergy to cephalosporins can receive penicillins with dissimilar side chains, irrespective of severity and time since the index reaction. However, for non-severe reactions, cross-reactivity patterns should be considered, and patients may tolerate other classes of beta-lactams.

Key considerations include:

• The severity of the previous reaction: Severe immediate hypersensitivity reactions necessitate avoiding all beta-lactam antibiotics.
• The type of previous reaction: Immediate-type vs. delayed-type hypersensitivity reactions have different management strategies.
• Cross-reactivity patterns: Ceftriaxone is a third-generation cephalosporin, and patients may tolerate other classes of beta-lactams.

For empiric coverage similar to ceftriaxone, options include:

• Aztreonam 1-2g IV every 8 hours
• Levofloxacin 750mg daily
• Moxifloxacin 400mg daily

In cases where beta-lactams are strongly preferred, desensitization protocols can be considered under specialist supervision 1. It is essential to document the nature of the allergic reaction in detail, as many reported "allergies" are actually non-immunologic adverse effects. If the original reaction was a rash occurring days after administration, it may represent a delayed hypersensitivity reaction rather than an IgE-mediated allergy, potentially allowing use of structurally different beta-lactams with caution. Consider infectious disease or allergy consultation for complex cases requiring beta-lactam therapy in the setting of documented allergy.

From the FDA Drug Label

WARNINGS Hypersensitivity Reactions 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. Serious acute hypersensitivity reactions may require the use of subcutaneous epinephrine and other emergency measures. In case of severe hypersensitivity reactions, treatment with ceftriaxone must be discontinued immediately and adequate emergency measures must be initiated

Ceftriaxone allergy management involves:

• Careful inquiry into the patient's history of hypersensitivity reactions to cephalosporins, penicillins, and other beta-lactam agents
• Cautious administration to patients with a history of allergy, particularly to drugs
• Discontinuation of treatment and initiation of emergency measures in case of severe hypersensitivity reactions
• Use of subcutaneous epinephrine and other emergency measures for serious acute hypersensitivity reactions 2

Contraindications include:

• Known hypersensitivity to ceftriaxone, its excipients, or other cephalosporins
• Premature neonates up to a postmenstrual age of 41 weeks
• Hyperbilirubinemic neonates
• Neonates requiring calcium-containing IV solutions 2

From the Research

Ceftriaxone Allergy Management

• Ceftriaxone is a third-generation cephalosporin, and its use in penicillin-allergic patients is considered safe due to its low cross-reactivity with penicillins 3, 4.
• The overall cross-reactivity rate between penicillins and cephalosporins is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 3.
• Ceftriaxone does not increase the risk of an allergic reaction in patients with penicillin allergy, according to a study published in The Journal of family practice 4.
• A case study reported a patient who experienced anaphylaxis after receiving ceftriaxone, despite tolerating cefazolin therapy, highlighting the importance of understanding the unique side chains of cephalosporins that can precipitate anaphylaxis 5.
• Ceftriaxone has been used to treat bacterial meningitis in adults, with a clinical cure rate of 100% in one study, and has been shown to be effective against pneumococcal meningitis, including strains resistant to penicillin and cephalosporins 6, 7.