Therapeutic Drug Monitoring-guided dosing of continuous piperacillin/tazobactam in critically ill cardiac surgery patients

Abstract Purpose: Critical illness and sepsis are associated with marked pharmacokinetic variability, complicating adequate dosing of β-lactam antibiotics. Data on pharmacokinetic/pharmacodynamic (PK/PD) target attainment and therapeutic drug monitoring (TDM) of piperacillin/tazobactam (TZP), a widely used β-lactam antibiotic, in cardiac surgical patients remain limited. This study evaluated PK/PD target attainment during continuous TZP infusion combined with daily TDM in a cardiac surgical intensive care unit (ICU). Methods: This single-center retrospective observational study included ICU patients receiving continuous TZP infusion with daily TDM. The PK/PD target was defined as 100% fT > 4× minimum inhibitory concentration (MIC) of Pseudomonas aeruginosa (≥ 64 mg/L), with concentrations of 32–<64 mg/L considered clinically acceptable (‘near-target exposure’). Overexposure was defined as concentrations > 100 mg/L. Target attainment and potential risk factors for non-attainment, including renal and cardiac failure, were analysed. Results: Among 105 patients, initial target attainment was only 27.6%, while 43.8% were overexposed. Overexposure was frequent in patients with severely impaired renal function (80.0%), whereas normal or augmented renal clearance predominantly resulted in near target exposure (57.1% and 81.8%, respectively). Most patients requiring extracorporeal organ support were overexposed during the initial therapy. Across all patients, TDM-guided dose adjustments increased target attainment to 50.0% and reduced overexposure to 12.9%. Conclusions: Standardized continuous TZP infusion did not ensure adequate target attainment in cardiac surgical ICU patients. Early and repeated TDM improved target attainment and reduced overexposure, particularly in patients with impaired renal function and extracorporeal organ support. Nevertheless, limited overall target attainment supports the need for more individualized dosing strategies.