Cross-Reactivity and Tolerability of Cephalosporins in Patients with Immediate Hypersensitivity to Penicillins

Background Studies performed since 1990 on samples of at least 30 subjects with a documented IgE-mediated hypersensitivity to penicillins have found a rate of positive responses to allergy tests with cephalosporins ranging from 0% to 27%. Objective We sought to assess the cross-reactivity with cephalosporins and evaluate the possibility of using cephalosporins in penicillin-allergic subjects. Methods We conducted a prospective study of 252 consecutive subjects who had suffered 319 immediate reactions (mostly anaphylaxis) to penicillins and had positive skin tests to at least 1 penicillin reagent. All patients underwent serum specific IgE assays for cefaclor, as well as skin tests with 3 aminocephalosporins (cephalexin, cefaclor, and cefadroxil), cefamandole, cefuroxime, ceftazidime, ceftriaxone, cefotaxime, and cefepime. Patients with negative results for the last 5 cephalosporins were challenged with cefuroxime axetil and ceftriaxone; those with negative results for aminocephalosporins were also challenged with cefaclor and cefadroxil. Results Ninety-nine participants (39.3%) had positive allergy tests for cephalosporins. Specifically, 95 (37.7%) were positive to aminocephalosporins and/or cefamandole, which share similar or identical side chains with penicillins. All 244 subjects who underwent challenges with cefuroxime axetil and ceftriaxone tolerated them. Of the 170 patients who underwent aminocephalosporin challenges, 3 reacted to cefaclor and 4 to cefadroxil. Conclusions Cross-reactivity between penicillins and cephalosporins seems to be mainly related to side chain similarity or identity. Subjects with an IgE-mediated hypersensitivity to penicillins could be treated with cephalosporins such as cefuroxime and ceftriaxone that have side-chain determinants different from those of penicillins and are negative in pretreatment skin testing.