Delayed hypersensitivity to cefazolin: report on a case involving lymphocyte transformation studies with different cephalosporins

Background: A cell-mediated immunopathogenic mechanism has been demonstrate d in only a few cases of cutaneous reactions to systemically administered c ephalosporins. Objective: The aim was to investigate the pathogenic mechanism of a maculo- papular rash experienced by a subject during cefazolin therapy. Methods and Results: Prick, intradermal, and patch tests were carried out u sing penicillin determinants, ampicillin, amoxicillin, cefazolin, cephaloth in, cefuroxime, ceftazidime, and ceftriaxone. Those tests for penicillin G and its determinants, as well as for ampicillin and amoxicillin, were negat ive. The patient displayed patch-test and delayed intradermal-test positivi ty to all the cephalosporins tested. No specific immunoglobulin E antibodie s were found for penicillins or cefazolin. The lymphocyte-transformation-te st results were negative for all the penicillins tested and showed a positi ve concentration-effect curve for cefazolin, ceftazidime, and ceftriaxone a t concentrations up to 50 mug/mL. At 100 mug/mL the responses decreased wit h all the cephalosporins tested. Challenges with penicillin G and amoxicill in were well tolerated, but the challenge with cefazolin was positive. Conclusions: The data of this case demonstrate delayed hypersensitivity to cefazolin. Patch tests and delayed-reading intradermal tests can be a simpl e and effective means of diagnosing this type of reaction. Both in vivo and in vitro studies indicate that the responses were directed toward a determ inant shared by all cephalosporins, but not by penicillins. The concentrati on of the cephalosporins used for the in vitro lymphocyte stimulation was c ritical, because at the concentrations normally used to test other beta -la ctams the response decreased. This phenomenon may be attributable to an imm unosuppressive, rather than toxic, effect.