Empirical piperacillin/tazobactam vs carbapenems to treat bloodstream infections due to ESBL enterobacterales: a propensity score-matched observational study conducted in an emergency department in Northern Italy

Background: Piperacillin/tazobactam is frequently used empirically in patients subsequently diagnosed with bloodstream infections (BSIs) due to extended-spectrum β-lactamase (ESBL) Enterobacterales, yet its effectiveness remains uncertain. Objective: This study aimed to compare piperacillin/tazobactam with carbapenems as empirical therapy for BSIs caused by ESBL-Enterobacterales. Methods: A single-centre retrospective study was conducted at Niguarda Hospital in Milan,Italy, enrolling consecutive patients with BSIs caused by ESBL-Enterobacterales treated empirically with either piperacillin/tazobactam or carbapenems from January 2015 to December 2023. The primary outcome was in-hospital all-cause mortality. Propensity Score Matching(PSM) was employed to mitigate potential confounding factors when assessing the association between empirical therapy and mortality. A sensitivity analysis was performed to determine the role of definitive piperacillin/tazobactam or carbapenems on patient outcomes. Results: A total of 264 patients were included in the study, median age was 72[64–81], 64% were males, 66% had sepsis and 17% septic shock. Among them, 200(76%) received empirical piperacillin/tazobactam and 64(24%) received carbapenems. After PSM adjustment, baseline characteristics were well balanced between the groups. Patients who received empirical piperacillin/tazobactam had a higher in-hospital mortality compared to those receiving empirical carbapenems (14.3% vs 3.5%, adjusted Risk Difference: 10%;95%CI: 2–19%). No difference in in-hospital mortality was observed when comparing definitive piperacillin/tazobactam to definitive carbapenems (6% vs 9%, Risk Difference: −2.5%; 95%CI: −9.2 − 4.2). Conclusion: Empirical piperacillin/tazobactam may be associated with higher mortality compared tocarbapenemswhen treating patients with BSI due to ESBL-Enterobacterales. Further larger studies are needed to confirm the results andto identify specific scenarios in which piperacillin/tazobactam may be safely used.