Testing Strategies and Predictors for Evaluating Immediate and Delayed Reactions to Cephalosporins

Although 1% to 2% of the general population carries a cephalosporin allergy label (CAL), we lack validated testing strategies and predictors of true allergy.

To identify cross-reactivity patterns and predictors of skin test positive (STP) in geographically disparate patients with a CAL.

A total of 780 adult patients labeled with a CAL or penicillin allergy label (PAL) with unknown tolerance of cephalosporins identified from the Austin Hospital (Melbourne, Australia) (n = 410) and Vanderbilt University Medical Center (Nashville, TN) (n = 370) between 2014 and 2018 underwent a standardized skin testing.

Of 328 patients with a CAL, 29 (8.8%) tested STP to ≥1 cephalosporin(s). There were no cefazolin or ceftriaxone STP, 0 of 452 (0%), in patients with a PAL only. Of 328 patients with a CAL, 16 (4.8%) were ampicillin STP. Eleven of 16 of these patients had an initial allergy label to cephalexin. Twenty of 29 cephalosporin STP patients demonstrated tolerance to a cephalosporin with a different R1 side chain, and 8 of 14 ampicillin STP patients demonstrated tolerance to ≥1 non-amino R1 group cephalosporin. Eleven of 13 patients STP to cefazolin were skin and ingestion challenge negative to all other penicillins and cephalosporins predicted by its distinct R1/R2 groups. Seven of 15 ceftriaxone STP patients demonstrated cross-reactivity with R1-similar cephalosporins. Time since the original reaction predicted STP testing to both penicillins, adjusted odds ratio (aOR) per year 0.93 (95% confidence interval [CI]: 0.90, 0.97), and cephalosporins, aOR per year 0.71 (95% CI: 0.56, 0.90).

Cephalosporin cross-reactivity is based on shared R1 groupings. Increasing time since the original reaction and the presence of a PAL with unknown cephalosporin tolerance predict a lower likelihood of cephalosporin STP.