Retrospective Study of Prolonged Versus Intermittent Infusion Piperacillin-Tazobactam and Meropenem in Intensive Care Unit Patients at an Academic Medical Center

Background: Prolonged infusions of A-lactams are increasingly being utilized because of increased antimicrobial resistance and a lack of new antibiotics in the pipeline. Methods: A retrospective, observational study evaluated adult patients who received at least 72 hours of piperacillin-tazobactam or meropenem in a medical and surgical intensive care unit (ICU) at an academic medical center. In the first 6 months of the study, all patients received conventional intermittent dosing; in the second 6 months, all patients received these antibiotics by prolonged infusions. The main outcome comparisons between groups were duration of ventilator support, duration of ICU and hospital length of stay, and in-hospital mortality. Results: A total of 121 patients were included: 54 patients in the intermittent (67% piperacillin-tazobactam, 33% meropenem) and 67 patients in the prolonged group (81% piperacillin-tazobactam, 19% meropenem). The prolonged group demonstrated a significant decrease in ventilator days (j7.2 days; 95% confidence interval [CI], j12.4 to j2.4), ICU length of stay (j4.5 days; 95% CI,j8.3 toj1.4), and hospital length of stay (j8.5 days; 95% CI,j18.7 toj1.2) compared with the intermittent group. The risk of in-hospital mortality was 12.4% in the prolonged infusion group and 20.7% in the intermittent infusion group corresponding to an odds ratio of 0.54 (0.18Y1.66). Conclusions: The results of this study show that the use of prolonged infusions of piperacillin-tazobactam and meropenem could potentially improve clinical outcomes in critically ill populations. As antibiotic resistance continues to increase in gram-negative pathogens, these A-lactam dosing strategies will be important for appropriate treatment.