Assessment of biliary excretion of piperacillin-tazobactam in humans

Piperacillin-tazobactam concentrations in serum and bile were measured intraoperatively in 10 patients undergoing cholecystectomy (group 1) and 5 cholecystectomized patients provided with external bile duct drainage (group 2), Each patient received a single intravenous dose of piperacillin at 1 g plus tazobactam at 0.5 g over 30 min, Drug concentrations in both serum and bile mere measured by high-performance liquid chromatography. In group 1 patients, serum and bile specimens and gallbladder wall fragments mere collected at mean times of 70 and 83 min postinfusion, respectively, The mean concentrations of piperacillin and tazobactam were, respectively, 69.1 +/- 41.5 (standard deviation) and 9.9 +/- 5.1 mu g/ml in serum, 630.4 mu g/ml (range, 24.8 to 1,194 mu g/ml) and 11,8 mu g/ml (range, 3.6 to 22 mu g/ml) in choledochal bile, 342.3 mu g/ml (range, 1,1 to 1,149 mu g/ml) and 7.7 mu g/ml, (range, 0,2 to 23.1 mu g/ml) in gallbladder bile, and 19.3 mu g/g (range, 9.7 to 223 mu g/g) and 2.9 mu g/g (range, 0.1 to 5.9 mu g/g) in the gallbladder mail, In group 2 patients, the amounts of drugs recovered in bile drainage obtained over 12 h mere 28.4 +/- 18.0 and 1.0 +/- 0.5 mg for piperacillin and tazobactam, respectively, Peak piperacillin and tazobactam concentrations in bile reached 355 +/- 242 and 10.8 +/- 3.2 mu g/ml, respectively. Comparison of drug levels in serum and bile suggests an underlying active secretion process for piperacillin elimination into the bile, unlike that of tazobactam. From a therapeutic viewpoint, given the concentrations of tazobactam recorded in bile fluid and tissue, the addition of this beta-lactamase inhibitor to piperacillin therapy might be of interest in the management of biliary tract infections, mostly in patients at risk of mixed aerobic-anaerobic infections due to beta-lactamase-producing organisms.