Pharmacokinetics and tissue penetration of single-dose cefotetan used for antimicrobial prophylaxis in patients undergoing colorectal surgery.

Abstract

The pharmacokinetics and tissue penetration of cefotetan were studied after a single injection of 2 g given intravenously for antimicrobial prophylaxis to 16 consecutive patients undergoing colorectal surgery. Concentrations in tissue greater than or equal to the MIC for 90% of the main pathogens tested were considered adequate. The elimination half-life at beta phase was 4.6 +/- 1.4 h, the total body clearance was 0.75 +/- 0.19 ml/kg/min, and the volume of distribution was 260 +/- 71 ml/kg. At the time of incision (33 +/- 16 min after the injection), cefotetan concentrations were 14.2 +/- 7 micrograms/g in abdominal-wall fat, 16.4 +/- 1 micrograms/g in epiploic fat, and 163 +/- 62 mg/liter in serum. At the time of surgical anastomosis (151 +/- 54 min), cefotetan concentrations were 33.3 +/- 6 micrograms/g in the colonic wall and 73 +/- 34 mg/liter in serum. Upon closure of the abdomen (216 +/- 76 min), cefotetan concentrations were 6.3 +/- 3 micrograms/g in abdominal-wall fat, 6.1 +/- 4 micrograms/g in epiploic fat, and 64 +/- 38 mg/liter in serum. Cefotetan tissue penetration was 10% into abdominal and epiploic fat and 46% into the colonic wall. Levels in tissue were compared with the MIC for 90% of the most frequently encountered pathogenic germs (Staphylococcus aureus, Bacteroides fragilis, and Escherichia coli). Adequate concentrations in tissue were obtained up to anastomosis but not upon closure. The authors therefore recommend the injection of an additional dose of 1 g before closure in order to ensure optimal efficacy throughout the surgical procedure.