Objective  To investigate the attainment rate of pharmacokinetic/pharmacodynamic (PK/PD) targets and trough concentration (C_min) of piperacillin-tazobactam (TZP) in patients with severe traumatic brain injury (STBI), analyze influencing factors, and develop a predictive model for clinical application.

Methods  A retrospective analysis was conducted on clinical data from STBI patients treated with TZP and undergoing therapeutic drug monitoring in the intensive care unit of our hospital between January 2021 and March 2025. PK/PD target attainment was evaluated. Patients were stratified by creatinine clearance (Ccr) into augmented renal clearance (ARC) group (Ccr≥130.0 mL·min^-1) and non-ARC group (Ccr<130.0 mL·min^-1). Based on a PK/PD target C_min>16 μg·mL^-1, patients were categorized into the target-attainment group (C_min>16  μg·mL^-1) and the non-attainment group (C_min≤16 μg·mL^-1). Multivariate Logistic regression was used to identify factors associated with subtherapeutic TZP C_min in STBI patients. A receiver operating characteristic (ROC) curve was plotted and a predictive model was constructed. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) under different dosing regimens and infusion durations.

Results  A total of 96 STBI patients were included, among whom 28 had pulmonary infections and 26 had urinary tract infections; Gram-negative bacteria were the predominant pathogens. The overall PK/PD target attainment rate in STBI patients was 32.29% (31/96), 31 patients were in the target-attainment group and 65 in the non-attainment group. There were 33 patients in the ARC group and 63 in the non-ARC group. C_min was significantly higher in patients with pulmonary or urinary tract infections than in those without infections (P<0.001). Patients with serum creatinine (SCr) ≥85 μmol·L^-1 had higher C_min levels than those with SCr <85 μmol·L^-1 (P<0.001). C_min was higher in the non-ARC group than in the ARC group (P<0.001). Ccr was an independent factor influencing subtherapeutic TZP C_min [OR=4.268, 95%CI (2.457, 5.864), P<0.001]. The optimal cut-off value of Ccr was 71.600 mL·min^-1, which achieved the best predictive efficacy. When the minimum inhibitory concentration was ≤16 μg·mL^-1, there were appropriate treatment regimens and infusion durations to meet the requirement of PTA >90%. For empirical treatment of STBI patients and STBI patients with ARC, only the 4.5 g (q6 h) administration regimen with an infusion time of 4 h achieved a cumulative response fraction (CFR) of over 90%. The incidence of adverse drug reactions in the 96 patients was 6.25% (6/96).

Conclusion  The PK/PD target attainment rate of TZP in STBI patients is relatively low. Ccr is an important factor influencing TZP C_min. The predictive model based on Ccr demonstrates considerable clinical value. Individualized precision therapy can be optimized in clinical practice by adjusting infusion strategies and implementing therapeutic drug monitoring.

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