Immunohaematological cross-allergenicity between penicillin and cephalothin in humans

Abstract

The immunogenicity of cephalothin and its cross-reactivity with penicillin were studied in a series of 174 adult patients receiving intravenous sodium cephalothin or intravenous penicillin-G.

Immunogenicity was indicated by a higher incidence of anti-cephalothin antibody in patients after having received the drug than in controls and by an increase in titre of anti-cephalothin antibody during administration of the drug. Cross-allergenicity was indicated by a high incidence of anti-cephalothin antibodies in patients receiving penicillin who had never received cephalothin and by an increase in anti-cephalothin antibody titre in patients receiving penicillin. Further, patients receiving cephalothin had a high incidence of anti-penicillin antibodies and the anti-penicillin antibody titre increased during cephalothin administration. Confirmation of cross-allergenicity was obtained by inhibition of haemagglutination by penicillin and cephalothin derivatives as well as by absorption of sera with erythrocytes sensitized with penicillin or cephalothin. Treatment of sera with 2-mercaptoethanol indicated that anti-cephalothin and anti-penicillin antibodies were largely of the IgM immunoglobulin class. A low incidence of positive direct Coombs tests was found in this series and the probable reasons for this are discussed.

Penicillin is the most common cause of drug-immune haemolysis for which serological evidence of a drug related antibody exists. Since there is clear immunohaematological evidence of cross-allergenicity between penicillin and cephalothin, it is surprising that haemolytic anaemia due to cephalothin administration has not as yet been reported. This may be due to the fact that neither cephalothin alone nor a cephalothin–anti-cephalothin–antibody complex are firmly bound to erythrocytes during therapeutic administration of the drug.