The biliary tract kinetics of some cephalosporin antibiotics

Perioperative antibiotic therapy reduces the risk of infection in some contaminated or potentially contaminated operations. Use in the high-risk patient undergoing biliary tract operation is well defined. An initial clinical study involving 54 patients undergoing elective cholecystectomy disclosed poor correlation between antibiotic levels obtained from gallbladder bile and cholecystographically disclosed function of the gallbladder. Sequential samples in 11 patients showed gallbladder antibiotic titers to increase, whereas levels of both the common duct bile and serum followed a decreasing hyperbolic curve. Six healthy, adult mongrel dogs were studied serially after insertion of a cholecystostomy tube, a T-tube in the common duct, and intravenous administration of cefazolin. In 3 of the animals, obstruction of the gallbladder was produced by precise ligation of the cystic duct. In the sham-operated biliary system, 45 to 60 min elapsed before adequate antibiotic levels were achieved in the gallbladder bile. Peak levels (100 μg/ml) were reached between 2 and 3 hr after administration and were maintained during the 5 hr study period. In the serum and common duct, peak concentrations were reached within minutes and a continuous decline was noted throughout the experiment. In the animals with obstructed cystic ducts, antibiotic levels in the gallbladder did not achieve concentrations greater than 4 μg/ml at any time. Multiple intravenous antibiotic administrations 2 and 4 hr apart failed to achieve higher levels in the obstructed gallbladder. Similar kinetics with lower concentrations were found with cephalothin. These results suggest that preoperative antibiotic administration in selected high-risk patients with radiographically 'visualized' gallbladders should best be initiated 2 hr before operation and that such administration will result in high concentrations of antibiotic in the serum, tissue, and common duct and gallbladder bile. Cystic duct obstruction cannot always be determined cholecystographically prior to operation, but, when present, cephalosporin penetration into gallbladder bile is relatively poor and slowly achieved.