Direct Coombs’Test Reactivity after Cephalothin or Cephaloridine in Man and Monkey

The development of positive direct Coombs' reactions (DCR) in humans during administration of drugs has attracted increasing attention in recent years. This association can be of practical importance since in some instances the Coombs' reactivity may also be associated with hemolytic anemia; notable examples have included methyldopa and penicillin (1–3). Preliminary studies indicate that 40–70% of patients given cephalothin may develop positive DCR (4,5). This unusually high incidence emphasizes the need to define possible mechanisms of red blood cell alteration or sensitization, and to establish any association with red cell damage that might influence their survival. Although structurally similar to cephalothin (6), cephaloridine has been reported to have caused a positive DCR in only one patient (7).

The present study was conducted to determine (1) the incidence of positive DCR, (2) relationships to serum antibiotic concentrations, and (3) possible associated red blood cell abnormalities in patients and rhesus monkeys treated with cephalothin or cephaloridine.

Materials and Methods. During the period January through June, 1967, 143 patients at University Hospital were observed during cephalothin therapy. Serial DCR were performed by washing 2% suspensions of red blood cells three times in normal saline in 10 × 75-mm tubes, decanting the supernatant fluid; 2 drops of Coombs' anti-human serum (Pfizer) were added and the contents centrifuged for 15 sec in a Clay-Adams serofuge. DCR were interpreted as 4+ to 1+ depending upon the degree of macroscopic agglutination; microscopic agglutination was recorded as ± and considered insignificant. Serial hemoglobin (cyanmet-hemoglobin) and hematocrit (micromethod) determinations were obtained twice weekly during cephalothin treatment (8).

The comparative effect in vitro on DCR of human and monkey erythrocytes exposed to graded concentrations of cephalothin or cephaloridine was also studied; 0.5 ml of blood was added to 0.5-ml dilutions of the antibiotics in normal saline and incubated for 4 hr at 37°.