Pharmacokinetics, target attainment and outcomes of piperacillin/tazobactam in critically ill patients receiving continuous infusion with therapeutic drug monitoring: a retrospective analysis

Abstract Objectives To provide real-world evidence on piperacillin exposure and outcomes in critically ill patients following the implementation of pharmacokinetic (PK)/pharmacodynamic (PD)-guided dosing in routine care. Methods This retrospective observational study included critically ill adults who received continuous piperacillin/tazobactam infusion between 2011 and 2019. Empiric doses were individualized using dosing software based on renal function and subsequently adjusted according to therapeutic drug monitoring (TDM) results. Drug exposure was defined as subtherapeutic (<32 mg/L), therapeutic (32–64 mg/L), moderately high (64–96 mg/L), or supratherapeutic (>96 mg/L). Results A total of 1538 critically ill patients with severe infections and sepsis of varying severity were included, and 3,090 piperacillin serum concentrations were analysed. Median daily piperacillin dose was 8,000 mg, median steady-state concentration 55 mg/L, and median clearance 6.25 L/h. At the first measurement, individualized empiric dosing resulted in 45.7% of patients being within the therapeutic range; after TDM-guided adjustment, target attainment increased to 62.4%. Subtherapeutic and supratherapeutic concentrations were uncommon among all TDM samples collected during individualized dosing (<32 mg/L: 12.8%; < 16 mg/L: 0.8%; > 96 mg/L: 11%). ICU mortality was 21.1 % in patients within the therapeutic range, 30.3 % in those with moderately high concentrations, and 44.1 % in those with supratherapeutic concentrations (p = 0.05). Women were 1.8 times more likely to present supratherapeutic concentrations. Conclusions A multimodal approach combining individualized empiric dosing, TDM, and continuous infusion ensured target attainment while reducing drug consumption. These findings support the integration of individualized, PK/PD-guided dosing into routine care for critically ill patients and highlight the need for further studies addressing sex-related pharmacokinetic variability.