Piperacillin reaches high concentrations in bile and target tissues of the biliary system: an experimental study in pigs

The antibiotic combination of piperacillin/tazobactam (TZP) is commonly utilized for preventing and treating infections in the biliary system, with piperacillin being the primary agent. Its effectiveness is closely related to the time with concentrations above the minimal inhibitory concentration (<i>T</i> > MIC) of the bacteria involved. The most frequently encountered bacteria associated with biliary system infections present with clinical breakpoint MIC values of 8 and 16 µg/mL. This porcine study aimed to apply microdialysis to assess target site piperacillin <i>T</i> > MIC 8, 16, and 32 (4× MIC 8) µg/mL in the biliary system. In eight healthy pigs (Danish Landrace breed, weight 78-82 kg), five microdialysis catheters were placed for sampling of piperacillin concentrations in the liver, the wall of the gallbladder, the bile in the gallbladder, the wall of the common bile duct (CBD), and the bile in the CBD. A bolus of TZP 4/0.5 g was administered intravenously, and microdialysates and blood samples were collected during an 8 h period. Ultrahigh performance liquid chromatography (UHPLC) was used to quantify the piperacillin concentrations. The mean <i>T</i> > MIC (%T > MIC) varied from 345 to 446 min (77%-99%), 261-446 min (58%-99%), and 200-444 min (42%-99%) for the MIC targets of 8, 16, and 32 µg/mL, respectively. The pharmacokinetic parameters in the bile were found to be different compared to the remaining compartments with higher AUC_0-8h and <i>C</i>_max values and longer <i>T</i>_1/2. Piperacillin displayed prolonged <i>T</i> > MIC in bile compared to plasma and the target tissues of the biliary system, approaching 100%<i>T</i> > MIC for the MIC targets of 8, 16, and 32 µg/mL.