Intraoperative serum concentrations of cefazolin and cefoxitin administered preoperatively at different times

The effect of administration time on the serum concentrations of cefazolin and cefoxitin achieved during surgery was studied. Patients about to undergo elective surgery were randomly selected to receive one of four antibiotic prophylaxis regimens. Two of the regimens consisted of cefazolin 20 mg/kg i.v. (as the sodium salt) administered either "on call" to the operating room or with anesthesia in the operating room. The other two regimens were identical except that cefoxitin 30 mg/kg i.v. (as the sodium salt) was substituted for cefazolin. Intraoperative blood samples for analysis of serum concentrations were obtained at the time of surgical incision, one hour after incision, and at wound closure. Forty patients completed the study (10 patients received each treatment). Mean projected cefazolin concentrations at the time of incision and at wound closure for both two-hour and three-hour operations were significantly higher after administration with anesthesia than after "on-call" administration. For cefoxitin, differences in projected concentrations for "on-call" administration versus administration with anesthesia were significant at the time of incision and at wound closure in a two-hour operation. At times corresponding to initial incision, projected free-cefoxitin concentrations were higher than those of cefazolin; however, projected free-cefazolin concentrations were higher than free-cefoxitin concentrations at wound closure for two-hour and three-hour operations. To ensure that antibiotic is present in serum throughout a two- or three-hour surgical procedure, cefoxitin should probably be administered at the induction of anesthesia. Cefazolin administered "on call" appears to be acceptable for maintaining serum concentrations throughout surgery of this duration.