Serology of antibodies to second- and third-generation cephalosporins associated with immune hemolytic anemia and/or positive direct antiglobulin tests

BACKGROUND: First-generation cephalosporins rarely caused immune hemolytic anemia (IHA). Second- and third-generation cephalosporins, especially cefot etan and ceftriaxone, are increasingly associated with severe, sometimes fa tal IHA. STUDY DESIGN AND METHODS: Samples from 53 patients with drug-induced IHA an d/or positive direct anti-globulin test (DAT) were tested. Patients' sera w ere tested against drug-treated red cells (RBCs) and untreated or enzyme-tr eated RBCs, with and without the addition of drug solution. Eluates from pa tients' RBCs were tested against drug-treated and untreated RBCs. RESULTS: Forty-three patients had antibodies to cefotetan, 8 to ceftriaxone , 1 to cefoxitin, and 1 to cefotaxime. All patients had a positive DAT; onl y anti-cefoxitin and anti-cefotetan were demonstrable in RBC eluates. Sera containing anti-cefoxitin, anti-cefotaxime, and anti-cefotetan reacted with drug-treated RBCs (100%) and untreated or enzyme-treated RBCs in the prese nce of drug (98% or 100%, respectively). All of the ceftriaxone antibodies reacted with untreated or enzyme-treated RBCs in the presence of drug, but those tested did not react with ceftriaxone-treated RBCs. In addition to ce fotetan-dependent antibodies, 19 (44%) and 14 (33%) of 43 sera contained dr ug-independent antibodies when tested with and without the presence of a po lyethylene glycol potentiator, respectively. CONCLUSION: Cefotetan is by far the most common cause of drug-induced IHA. All cefotetan antibodies and the single examples of cefoxitin and cefotaxim e antibodies reacted with drug-coated RBCs, and most, in contrast to the re actions of antibodies to first-generation cephalosporins (e.g., cephalothin ), also reacted with RBCs (not treated with drug) in the presence of the dr ug. Ceftriaxone antibodies reacted only by the latter mechanism. Drug-indep endent antibodies (i.e., those reacting without any drug being present) wer e detected in 33 to 44 percent of patients' sera containing cefotetan antib odies, depending on the sensitivity of the method used.