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Abstract

Introduction: Piperacillin/tazobactam (PTZ) requires free, non-protein bound serum drug concentrations to remain above the minimum inhibitory concentration for 50% of the dosing interval (50% fT>MIC) in order to achieve maximal bactericidal activity. Current data has shown that traditional dosing regimens have not been able to achieve sufficient time above the MIC. However, prolonging the infusion time of each PTZ dose to four hours has shown a higher probability of reaching this target with lower total daily doses and may have mortality benefits in patients with a higher severity of illness. Hypothesis: We hypothesized that the superior pharmacodynamic profile of prolonged-infusion (PI) PTZ regimens will result in a lower rate of in-hospital mortality in critically ill patients. Methods: This is an IRB approved, single center, retrospective, observational cohort study designed to evaluate mortality outcomes in patients pre- and post-implementation of a four hour PI dose optimization protocol. All adult patients admitted to the intensive care unit (ICU) receiving? 48 hours of a PTZ regimen were included. Patients were excluded if they were neutropenic, diagnosed with cystic fibrosis, received a concomitant β-lactam antibiotic, or grew an organism resistant to PTZ. Results: A total of 400 patients were included in the study. Baseline characteristics were similar in each cohort. The primary endpoint, in-hospital mortality, was 5% lower in the PI cohort (16% vs. 21%; P = 0.3). ICU mortality was also reduced (6.5% vs. 8%; P = 0.7), as well as both mean hospital LOS (9.1 days vs. 10.7 days; P = 0.39) and ICU LOS (7.3 days vs. 8.5 days; P = 0.15). The mean duration of mechanical ventilation was significantly lower in the PI cohort (5.6 days vs. 9.7 days; P = 0.05), as was the mean number of doses received per patient (23 vs. 26; P = 0.02). Conclusions: Despite receiving fewer doses of PTZ, patients in the PI cohort demonstrated a trend towards decreased morbidity and mortality, although this difference was not statistically significant. Larger prospective trials are needed to further delineate the role of PI-PTZ in the critically ill.