Abstract
OBJECTIVE: To examine the effect of a loading dose (LD) for extended infusion piperacillin/tazobactam on clinical outcomes. METHODS: This single-centre, retrospective cohort study evaluated adult patients with Gram-negative bacteraemia who received extended infusion piperacillin/tazobactam for ≥48 hours between 2015 and 2022. In December 2019, the study institution developed a policy that automatically ordered a piperacillin/tazobactam LD whenever piperacillin/tazobactam was prescribed. The study compared patients who received piperacillin/tazobactam LD to those who did not. The primary endpoint was 30-day all-cause mortality. Key secondary endpoints included clinical cure, 14-day all-cause mortality, in-hospital all-cause mortality and microbiologic cure. Logistic regression modelling was performed to control for confounding variables. RESULTS: A total of 151 patients were included in the analysis, with 84 patients in the LD group and 67 patients in the no LD group. Baseline characteristics were similar in both treatment groups, except for immunocompromised status, severity of illness and serum creatinine, with most mortality prognosticators in the LD group. In the bivariate analysis, 30-day mortality was 10.7% (9/84) in the LD group compared to 9.0% (6/67) in the no LD group (P = 0.72). This was consistent with the multivariable logistic regression model (adjusted OR, 0.71; 95% CI, 0.21-2.41). CONCLUSIONS: Overall, we observed no significant association between LD for extended infusion piperacillin/tazobactam and mortality, and no signal that use of LD was associated with more adverse events. We hypothesize a potential benefit of LD administration for severely ill patients, but larger adequately powered prospective cohorts or randomized trials are needed to examine this.