Auburn University Harrison School of Pharmacy, United States
Introduction: Piperacillin-tazobactam (PTZ) is a commonly prescribed antimicrobial in the intensive care unit (ICU). It is well established that extended infusion (EI) PTZ improves outcomes versus traditional dosing. Two different dosing strategies (3.375g and 4.5g) have been implemented since the adoption of EI dosing. A Monte Carlo simulation observed probability of target attainment (PTA) for the two strategies, but they have not been compared in-vivo. The objective was to compare 3.375g versus 4.5g of PTZ to determine if either leads to greater clinical improvement.
Methods: This is a retrospective comparison of two different EI PTZ dosing strategies. The primary endpoint is clinical success. Secondary outcomes include death during hospitalization, duration of PTZ therapy, duration of hospital and ICU stay, incidence of acute kidney injury (AKI), and worsening of infection. Any patient admitted to the ICU between January 1 and December 31, 2022 who received at least 72 hours of EI PTZ was included. Those with a creatinine clearance below 20 mL/min or receiving dialysis at baseline were excluded. Patients were excluded if it was ultimately determined that they did not have an infection. Sample size was not calculated due to the design. Statistics were calculated with SPSS software. The primary outcome was evaluated with Chi Square. Incidences of death and AKI were analyzed with Fisher's Exact and durations of therapy and ICU and hospital stay with Mann-Whitney U. A p value below 0.05 was considered significant.
Results: A total of 36 patients were included in the 3.375g cohort and 23 in the 4.5g cohort (n=59). The primary outcome occurred in 50% of patients in the 3.375g cohort and 83% of patients in the 4.5g cohort (p=0.012). Death occurred in one patient (4%) in the 4.5g cohort and five patients (14%) in the 3.375g cohort. AKI occurred in 22% vs 13% in the 3.375g vs 4.5g cohorts, respectively (p=0.502). Hospital and ICU length of stay were 11 (IQR 7-18) and 8 (IQR 3-14) in the 3.375g cohort and 11 (IQR 7-16) and 8 (IQR 4-12) in the 4.5g cohort, respectively.
Conclusions: The results of this analysis confirm results of prior in vitro analyses. Extended infusion PTZ results in better clinical success rates when the 4.5 g dosing strategy is utilized, with no differences in AKI, death, or lengths of stay.
