Does aztreonam cross-react with any cephalosporins, and if so which?

Aztreonam Cross-Reactivity with Cephalosporins

Aztreonam has no cross-reactivity with any cephalosporin except ceftazidime (and cefiderocol), which share an identical R1 side chain with aztreonam. 1

The Exception: Ceftazidime and Cefiderocol

• Ceftazidime is the only commonly used cephalosporin that cross-reacts with aztreonam due to their shared identical R1 side chain structure. 1

• Cefiderocol also shares this identical side chain and should be avoided in aztreonam-allergic patients. 1

• Patients with confirmed ceftazidime allergy should not receive aztreonam without prior allergy testing. 1

• Conversely, patients who are aztreonam-allergic may be treated with all beta-lactams except ceftazidime and cefiderocol. 1

Safe Cephalosporins in Aztreonam Allergy

• All other cephalosporins (cefazolin, cefepime, ceftriaxone, cefuroxime, cephalexin, cefaclor, etc.) can be safely administered to aztreonam-allergic patients without additional precautions. 1

• No cross-reactivity has been demonstrated between aztreonam and these cephalosporins in either IgE-mediated or T-cell–mediated hypersensitivity reactions. 1, 2

Clinical Application

• In patients with penicillin or cephalosporin allergy (other than ceftazidime/cefiderocol), aztreonam may be administered without prior testing. 1

• This recommendation applies to both immediate-type and delayed-type reactions. 1

• The FDA label confirms that aztreonam is "rarely cross-reactive with other beta-lactam antibiotics," though it recommends caution in any patient with beta-lactam allergy history. 3

Mechanistic Basis

• Cross-reactivity between beta-lactams is determined by R1 side chain similarity, not the shared beta-lactam ring structure. 1, 4

• Aztreonam's unique side chain differs from all cephalosporins except ceftazidime and cefiderocol. 1

• Research studies with 98 cephalosporin-allergic patients showed only 3.1% had positive skin tests to aztreonam, and these were specifically in patients allergic to ceftazidime. 5

• Studies of 45 beta-lactam-allergic patients demonstrated 100% tolerance to aztreonam challenges when skin tests were negative. 6

• A study of 214 patients with T-cell–mediated penicillin hypersensitivity showed zero cross-reactivity with aztreonam. 2

Important Caveat

• While immunologic cross-reactivity is negligible, aztreonam itself can cause hypersensitivity reactions in patients with or without prior beta-lactam exposure, as it is an independent allergen. 3

• This represents de novo sensitization rather than cross-reactivity. 1