Cross-reactivity of cefotetan and ceftriaxone antibodies, associated with hemolytic anemia, with other: cephalosporins and penicillin

Am J Clin Pathol. 2002 Aug;118(2):256-62. doi: 10.1309/JFJE-VUKN-221T-G6EV.


Most drug-induced immune hemolytic anemias since the late 1980s have been caused by the second- and third-generation cephalosporins, cefotetan and ceftriaxone, respectively. Cross-reactivity of cefotetan and ceftriaxone antibodies with other cephalosporins or penicillin has been studied only minimally. We tested 7 serum samples previously identified to contain cefotetan antibodies and one serum sample previously identified to contain ceftriaxone antibodies against 9 other cephalosporins, penicillin, and 7-aminocephalosporanic acid in the presence of RBCs and also used hapten inhibition to indicate cross-reactivity. Serum samples containing cefotetan antibodies showed some cross-reactivity with cephalothin and cefoxitin (and to a much lesser extent with penicillin and ceftazidime). The ceftriaxone antibodies showed very weak cross-reactivity with cefotaxime, cefamandole, and cefoperazone. There was very little cross-reactivity between cefotetan antibodies and the drugs tested in the present study. We have no data to determine whether the in vitro data relate to in vivo reactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Hemolytic / immunology*
  • Antibodies / immunology*
  • Cefamandole / immunology
  • Cefoperazone / immunology
  • Cefotaxime / immunology
  • Cefotetan / immunology*
  • Cefoxitin / immunology
  • Ceftriaxone / immunology*
  • Cells, Cultured
  • Cephalosporins / immunology*
  • Cephalothin / immunology
  • Cross Reactions
  • Humans
  • Models, Chemical
  • Penicillins / immunology*


  • Antibodies
  • Cephalosporins
  • Penicillins
  • Cefotetan
  • Cefamandole
  • Cefoxitin
  • Ceftriaxone
  • Cefoperazone
  • 7-aminocephalosporanic acid
  • Cefotaxime
  • Cephalothin