Can cefazolin be used instead of ceftriaxone for tetanus in a patient with a documented ceftriaxone allergy?

Cefazolin Can Be Safely Used in Patients with Ceftriaxone Allergy

Cefazolin is safe to use in patients with a documented ceftriaxone allergy because these two cephalosporins have completely different R1 side chains, making cross-reactivity negligible. 1, 2

Understanding the Mechanism of Cross-Reactivity

Cross-reactivity between cephalosporins depends entirely on R1 side chain similarity, not the shared beta-lactam ring structure 1, 2. This is a critical concept that many clinicians misunderstand.

• Cefazolin has a unique side chain structure that differs from all currently available penicillins and most other cephalosporins, including ceftriaxone 1
• The reaction rate to cefazolin among patients with confirmed penicillin allergy is only 0.8% (95% CI: 0.13%-4.1%), demonstrating its exceptional safety profile 1
• Ceftriaxone and cefazolin do not share side chains, so tolerance of one does not predict tolerance of the other, but more importantly, allergy to one does not predict allergy to the other 3

Clinical Decision Algorithm

Step 1: Determine the Type of Ceftriaxone Reaction

For immediate-type reactions (urticaria, angioedema, bronchospasm, anaphylaxis occurring within 1-6 hours):

• Cefazolin can be used safely regardless of severity or timing of the ceftriaxone reaction 2
• Consider administering the first dose in a monitored setting if the ceftriaxone reaction was severe and recent 4

For delayed-type reactions (maculopapular rash, delayed urticaria occurring after 1 hour):

• Cefazolin can be used without restriction 2
• No special monitoring is required 4

Step 2: Identify Absolute Contraindications

Avoid cefazolin only if the patient experienced:

• Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome with ceftriaxone 2, 4
• Organ-specific reactions such as hemolytic anemia, drug-induced liver injury, or acute interstitial nephritis 4
• In these cases, all beta-lactam antibiotics should be avoided 4

Important Caveats

A documented case report demonstrates that tolerance to cefazolin does not predict tolerance to ceftriaxone 3. A 48-year-old woman tolerated cefazolin for 4 days but developed anaphylaxis to ceftriaxone, with skin testing confirming that the allergic determinant was the unique ceftriaxone R2 side chain 3. This case reinforces that each cephalosporin should be evaluated based on its individual side chain structure.

The reverse is equally true: allergy to ceftriaxone does not predict allergy to cefazolin due to their dissimilar side chains 2, 3.

Documentation Requirements

When prescribing cefazolin to a patient with ceftriaxone allergy, document the type and timing of the original ceftriaxone reaction in the medical record 4. This ensures appropriate clinical context and helps avoid unnecessary avoidance of effective antibiotics.