Adverse Reactions to Cephalothin and Cephapirin

The pharmacokinetics and tolerance of cephalothin and cephapirin (a semisynthetic cephalosporin), were evaluated in 40 healthy subjects. Each of the drugs was administered to 15 subjects in increasing doses up to 2.0 g by rapid intravenous infusion four times daily. Equivalent volumes of saline solution were given to 10 control subjects. An illness resembling serum sickness developed in all 30 drug-treated subjects within two to four weeks, whereas the control subjects remained well. The illnesses seemed to result from hypersensitivity to the drugs or their degradation products and not from other chemical or infectious agents. The extraordinarily high rate of reactions was apparently due to the rate of drug infusion or the high doses employed or both. Physicians should be alert to the possibility of similar reactions among hospitalized patients who are receiving large doses of cephalosporins by the intravenous route. (N Engl J Med 290:424–429, 1974)