Recent studies have increasingly questioned the efficacy and safety of piperacillin–tazobactam (TZP) in septic patients, particularly those with healthcare-associated intra-abdominal infections (hcIAI). This study assessed clinical outcomes in hcIAI patients receiving microbiologically documented TZP (dTZP) treatment.

We conducted a retrospective, propensity score (PS)-matched observational study in the surgical intensive care unit (ICU) of a tertiary university hospital, including adult patients admitted with hcIAI between 1999 and 2019. The primary endpoint was 1-month mortality. Univariate and multivariate logistic regression analyses were performed. A 1:1 PS-matching procedure was applied to reduce baseline imbalances. Sensitivity analyses included inverse probability of treatment weighting (IPTW). Subgroup analyses assessed treatment-effect heterogeneity.

A total of 454 patients were analyzed. In univariate analysis, despite a higher rate of adequacy in empirical therapy (70% vs . 56%, p  = 0.008), patients receiving dTZP had higher 1-month mortality rates (44% vs. 25%, p   <  0.001). Multivariate analysis identified dTZP treatment (OR = 2.31, 95%CI [1.35–3.95], p  = 0.002), SOFA score (OR = 1.29, 95%CI [1.20–1.40], p   <  0.001), age (OR = 1.04, 95%CI [1.02–1.06], p  = 0.001), and non-fermenting Gram-negative bacilli isolation (OR = 1.89, 95%CI [1.01–3.51], p  = 0.045) as independent predictors of 1-month mortality. In the PS-matched cohort, dTZP use remained associated with higher 1-month mortality rates (40% vs. 27%, p  = 0.025). However, IPTW analysis did not reach statistical significance, and no mortality signal was identified in patients included after 2010.

dTZP administration in hcIAI was associated with increased 1-month mortality in most analyses, though sensitivity analyses were not uniformly positive, and residual confounding cannot be excluded.