Ceftizoxime-induced hemolysis due to immune complexes: case report and determination of the epitope responsible for immune complex-mediated hemolysis.
BACKGROUND
Several occurrences of immune complex-mediated, cephalosporin-induced intravascular hemolysis have been reported. This report describes the first case of hemolytic anemia caused by an immune-complex mechanism associated with ceftizoxime and delineates the epitope responsible for hemolysis.


METHODS
The patient's serum was tested for antibody that reacted with five penicillins and 30 cephems (all types of cephalosporins) by using protocols to detect drug-adsorption and immune-complex mechanisms. The patient's antibody that formed immune complexes with ceftizoxime reacted with 10 of 30 cephems. These 10 drugs were classified as oxime-type cephalosporins, which have a common structural formula consisting of [(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetoamido] at the C7 position on 7-aminocephalosporinic acid with or without substitution at the C3 position.


CONCLUSIONS
The patient's antibody recognized a common structure in 10 oxime-type cephalosporins, and immune complexes formed by the antibody specifically or nonspecifically bound to red cell membranes. Therefore, when intermittent antibiotic therapy is required, as in this case, care should be taken in antibiotic selection to avoid drug-induced hemolytic anemia. In addition, when this type of hemolysis is observed, tests for antibody that reacts by adsorption and immune-complex mechanisms should be performed against penicillins and cephems to select antibiotics not showing a cross-reaction.
Endoh
T
T
Department of Laboratory Diagnosis, Sapporo Medical University School of Medicine, Japan.
Yagihashi
A
A
Sasaki
M
M
Watanabe
N
N
D000327:Adsorption; D000368:Aged; D000707:Anaphylaxis / Q000139:chemically induced; D000743:Anemia, Hemolytic / Q000139:chemically induced*; D000918:Antibody Specificity; D001772:Blood Cell Count; D001780:Blood Coagulation Tests; D001798:Blood Proteins / Q000032:analysis; D001991:Bronchitis / Q000188:drug therapy; D015296:Ceftizoxime / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D002511:Cephalosporins / Q000737:chemistry / Q000145:classification; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D003429:Cross Reactions; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced; D004342:Drug Hypersensitivity / Q000150:complications*; D000939:Epitopes / Q000276:immunology; D004910:Erythrocyte Membrane / Q000737:chemistry; D017809:Fatal Outcome; D006801:Humans; D007105:Immune Complex Diseases / Q000097:blood / Q000139:chemically induced*; D008297:Male; D015394:Molecular Structure
D001798:Blood Proteins; D002511:Cephalosporins; D000939:Epitopes; D015296:Ceftizoxime