Cefotetan-induced hemolytic anemia: a case report and review of the literature.

Cefotetan disodium-induced hemolytic anemia has been reported previously, and some of these cases have been severe or fatal. We describe a case of severe hemolytic anemia that occurred in an 80-year-old woman who received cefotetan prophylactically after surgery for a small bowel obstruction. Eight days after the first dose of cefotetan, the patient developed a severe Coomb test-positive hemolytic anemia. Using flow cytometry, we demonstrated cefotetan-specific antibodies in her posttreatment serum, which were detectable at a serum dilution up to 1:10 000. The patient received corticosteroid therapy and blood transfusions, with improvement of her hematologic parameters, but died 54 days after admission for respiratory failure. To our knowledge, this is the first use of flow cytometry for the detection of cefotetan-induced red blood cell antibodies. This technique offers a sensitive, rapid, objective method for detecting drug-induced antibodies.

[Toxicological studies on a new cephamycin, MT-141. XI. Immunological properties].

Immunogenicity, eliciting antigenicity of MT-141 and its cross-reactivity with other beta-lactam antibiotics were studied in mice, guinea pigs and rabbits. The results were as follows. Injections of MT-141 failed to produce IgE-type antibody in mice but injections of the MT-141 conjugated to rabbit serum albumin produced a trace of IgE-type antibody. No antibody was produced in the guinea pigs immunized with the MT-141 conjugated to rabbit serum albumin in alum or Freund's complete adjuvant. The conjugated MT-141 also failed to elicit anaphylactic shock in the immunized guinea pigs. The subcutaneous treatments with MT-141 in Freund's complete adjuvant produced an amount of hemagglutination antibody in rabbits. The intravenous treatments with MT-141 produced no antibody in rabbits. When rabbits were subcutaneously immunized with the MT-141 conjugated to rabbit serum albumin in Freund's complete adjuvant, production of specific antibody in the rabbits was demonstrated by observations of passive cutaneous anaphylaxis and hemagglutination. The results of hapten-induced inhibition of passive hemagglutination, passive cutaneous anaphylaxis, anaphylactic shock and hemagglutination by using conjugates of antibiotics and rabbit serum albumin as immunogens and conjugates of antibiotics and bovine gamma-globulin as eliciting antigen showed that MT-141 did not cross-react with other antibiotics. MT-141 did not cause the in vitro direct Coombs' reaction in the human blood even at a high concentration of 160 mg/ml. It is concluded from these results that immunological activity of MT-141 preparation is weak.

Immunological studies on CS-1170, a new semisynthetic cephamycin antibiotic.

The antigencity of CS-1170, a newly developed semi-synthetic cephamycin, and it's cross-reactivity with beta-lactam antibiotics were studied. The antigencity was confirmed by the following tests: 1)the passive hemagglutination test with anti-CS-1170 antisera of guinea pigs immunized with CS-1170 plus Freund complete adjuvant, 2)lymphocyte proliferation response in vitro stimulated with this drug in the guinea pigs, 3) the PCA test using mice immunized with CS-1170-protein conjugates. The antibody to CS-1170 appears to be directed to the acyl side chain because cyanomethylthioacetylglycine, an univalent acyl side chain of the CS-1170, can significantly cross-react with the antibody. A methoxy group on the C-7 alpha-position of the antibiotic plays no important part for the antigenic specificity of the molecule. The cross-reactivity of CS-1170 with cefazolin, cephalothin, benzylpenicillin and ampicillin was only to a minimal extent in the passive hemagglutination test. The cross-reactivity of CS-1170 and the related antibiotics was not observed among them in the PCA system with IgE anti-CS-1170. These findings support a conclusion that CS-1170 is one of beta-lactam antibiotic with an immunologically minimal cross-reactivity to the related antibiotics.