Abstract
PURPOSE: Antimicrobial resistance increases with the use of broad-spectrum antibiotics. Studies evaluating antibiotic stewardship are in high demand. Is piperacillin/tazobactam non-inferior to carbapenems regarding 30-day mortality among patients with bloodstream infections caused by extended-spectrum beta-lactamase-producing Enterobacterales? METHODS: This retrospective, multicenter, non-inferiority, cohort study assessed adult patients with bloodstream infections caused by extended-spectrum beta-lactamase-producing Enterobacterales in southern Sweden from 2013 to 2022. Patients were categorized according to the first therapy they received two consecutive doses of (piperacillin/tazobactam or a carbapenem). The primary outcome was 30-day all-cause mortality, measured from when the positive blood cultures were taken. The absolute risk difference for this outcome was calculated for all patients, and two propensity score matched cohorts (empirical and effective), with two different delta limits (5% and 2%). Secondary outcomes included intensive care unit admission, early clinical response, superinfections, relapsed infection and one-year mortality. RESULTS: A total of 644 patients were included. In the piperacillin/tazobactam group, 26/309 patients met the primary outcome, compared to 27/335 patients in the carbapenem group. The absolute risk difference (-0.4%) was statistically significant in the propensity score matched empirical cohort [1-sided 97.5% confidence interval]: -∞ to 4.0, p = 0.008). Piperacillin/tazobactam was non-inferior to carbapenems for all the secondary outcomes in the same cohort, except for the early clinical response. CONCLUSION: Our findings indicate that piperacillin/tazobactam is non-inferior to carbapenems for treating extended-spectrum beta-lactamase-producing Enterobacterales bloodstream infections, with an acceptable 5% increase in 30-day mortality. We suggest that piperacillin/tazobactam should be used more frequently to decrease antimicrobial resistance.