Piperacillin concentrations in bile—a prospective observational study in ERCP patients

Abstract Surgical site infections complicate up to 30% of hepato-pancreato-biliary (HPB) procedures, with biliary obstruction potentially increasing this risk. Recent studies suggest prophylactic piperacillin/tazobactam (TZP) may offer superior protection compared to cephalosporins. Piperacillin concentrations must exceed the minimum inhibitory concentration (MIC) of key bacterial pathogens in the surgical field, commonly exhibiting MICs of 8 and 16 mg/L. The aim of the study was to ​ evaluate piperacillin concentrations in plasma and bile over time relative to MIC targets (8–16 mg/L), and to evaluate the impact of biliary obstruction. Ninety-nine patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) received an intravenous dose of TZP (4/0.5 g), followed by simultaneously plasma and bile sampling at random intervals. In a post hoc analysis, the patients were stratified by bilirubin levels: non-obstructed (≤ 25 µmol/L) and obstructed (> 25 µmol/L). Piperacillin was quantified using ultra-high-performance liquid chromatography. In non-obstructed patients ( n = 77), biliary concentrations exceeded the MIC targets ≥ 245 min (peak 3,105 mg/L), while plasma levels remained above the MIC targets for 190 min (peak 431 mg/L). In the obstructed group ( n = 22), bile concentrations were inconsistent, with malignant obstruction associated with subtherapeutic levels. Plasma concentrations were similar between groups. Piperacillin provides sustained biliary concentrations above MIC targets. Malignant obstruction may compromise biliary drug exposure and warrants consideration of alternative dosing strategies. Clinical trial : The study qualified as a medical trial and was registered at the EU Clinical Trials Register with an EudraCT number: 2021-002629-95. The date of registration and approval for inclusion of patients was November 11th, 2022.