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 4 g plus tazobactam at 0.5 g over 30 min. Drug concentrations in both serum and bile were measured by high-performance liquid chromatography. In group 1 patients, serum and bile specimens and gallbladder wall fragments were 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 microg/ml in serum, 630.4 microg/ml (range, 24.8 to 1,194 microg/ml) and 11.8 microg/ml (range, 3.6 to 22 microg/ml) in choledochal bile, 342.3 microg/ml (range, 1.1 to 1,149 microg/ml) and 7.7 microg/ml, (range, 0.2 to 23.1 microg/ml) in gallbladder bile, and 49.3 microg/g (range, 9.7 to 223 microg/g) and 2.9 microg/g (range, 0.1 to 5.9 microg/g) in the gallbladder wall. In group 2 patients, the amounts of drugs recovered in bile drainage obtained over 12 h were 28.4 +/- 18.0 and 1.0 +/- 0.5 mg for piperacillin and tazobactam, respectively. Peak piperacillin and tazobactam concentrations in bile reached 358 +/- 242 and 10.8 +/- 4.2 microg/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.[1]References
- Assessment of biliary excretion of piperacillin-tazobactam in humans. Westphal, J.F., Brogard, J.M., Caro-Sampara, F., Adloff, M., Blicklé, J.F., Monteil, H., Jehl, F. Antimicrob. Agents Chemother. (1997) [Pubmed]
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