Purpose of the Study. Beta lactams are the most common agents involved in allergic reactions to antibiotics. There appears to be less cross-reactivity between penicillin and the newer generation cephalosporins. These latter agents might be associated with specific immunologic responses that do not cross-react with penicillins or other cephalosporins. These investigators examined the scope of immunoglobulin E (IgE) responses to various cephalosporins and penicillins in children and adults with histories compatible with cephalosporin allergy.
Study Population. Six children and 24 adults who had experienced urticaria/angioedema or anaphylaxis after exposure to injectable cephalosporins were selected for study. Reactions had occurred 1 to 48 months before evaluation. All 6 children had reacted to ceftriaxone, and 5/6 had suffered anaphylaxis.
Methods. All participants were skin tested with penicilloylpolylysine, minor determinant mixture, penicillin G, ampicillin, and amoxicillin; also, cephalothin, cefuroxime, ceftazidime, cefotaxime, and ceftriaxone. The various cephalosporins were tested at 2 mg/mL, a concentration previously shown to be a nonirritant in healthy control subjects. Radioallergosorbent tests (RASTs) were also performed to benzylpenicilloyl-polylysine, amoxicilloyl-polylysine, ampicilloyl-polylysine, and to the various cephalosporins conjugated to polylysine.
Results. All 6 children had positive skin tests (1 prick, 5 intradermal) for the culprit drug, but none had positive RASTs. No child reacted to any of the other cephalosporins or to any penicillin reagents. Among the adults, all but 2 individuals had positive skin tests, and 9 had positive RASTs to the culprit drugs. No one had positive RASTs with negative skin tests. Two adults had a total of 3 completely negative test batteries, including agents that had caused anaphylaxis 24, 40, and 45 months earlier. A total of 10 adults reacted to >1 cephalosporin, and there was no compelling pattern of cross-reactivity. Similarly, there was no pattern apparent in the 4 patients who reacted to penicillin reagents.
Conclusions. Most patients with histories of allergic reactions to cephalosporins are sensitized to determinants specific for the given drug, although some display cross-reactivity to other cephalosporins. A few individuals display reactivity to penicillin determinants, but this is not predicted by culprit drug or nature of reaction.
Reviewer’s Comments. This study focused on reactions after parenterally administered cephalosporins and clearly highlights the low but unpredictable incidence of cross-reactivity among these agents and the penicillins. Pediatricians dealing with the quandary of a child with a history of suspected reaction from an orally administered preparation in the outpatient setting should realize that other cephalosporins might be tolerated just fine. Because there are no reagents for in vivo or in vitro testing for these oral cephalosporins, the only test is administration followed by a couple hours of observation in the office. For the hospitalized child with a history of allergy to an injected cephalosporin and in need of such now, it makes sense to skin test first with the agent(s) to be considered. If the history is one of reacting to an orally administered cephalosporin, it is probably even likelier that the parenteral agent would be well-tolerated. However, because most severe reactions follow injected drug at any age, it would be wise to skin test with the desired injectable cephalosporin first. Finally, the authors described 2 adults with histories of anaphylaxis but with currently negative tests, as mentioned above. These cases represented some of the longest intervals from time of reaction to evaluation date among all the patients studied. Drug allergy often wanes over months and years, and this can happen even when the initial reactions were life-threatening.
- Copyright © 2002 by the American Academy of Pediatrics