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Piperacillin/tazobactam versus carbapenems for 30-day mortality in patients with ESBL-producing Enterobacterales bloodstream infections: a retrospective, multicenter, non-inferiority, cohort study

Månsson, Thomas Sahlström LU orcid ; Askemyr, Alice LU ; Sunnerhagen, Torgny LU orcid ; Tham, Johan LU ; Riesbeck, Kristian LU orcid and Mellhammar, Lisa LU (2025) In Infection
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... (More)
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. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Infection
publisher
Urban und Vogel
external identifiers
  • pmid:40238082
ISSN
0300-8126
DOI
10.1007/s15010-025-02496-x
language
English
LU publication?
yes
id
1cd3b106-4f26-4273-b39c-d13e9e8c9794
date added to LUP
2025-04-17 08:08:56
date last changed
2025-04-18 03:32:01
@article{1cd3b106-4f26-4273-b39c-d13e9e8c9794,
  abstract     = {{Purpose<br/>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?<br/><br/>Methods<br/>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.<br/><br/>Results<br/>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.<br/><br/>Conclusion<br/>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.}},
  author       = {{Månsson, Thomas Sahlström and Askemyr, Alice and Sunnerhagen, Torgny and Tham, Johan and Riesbeck, Kristian and Mellhammar, Lisa}},
  issn         = {{0300-8126}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{Urban und Vogel}},
  series       = {{Infection}},
  title        = {{Piperacillin/tazobactam versus carbapenems for 30-day mortality in patients with ESBL-producing Enterobacterales bloodstream infections: a retrospective, multicenter, non-inferiority, cohort study}},
  url          = {{https://lup.lub.lu.se/search/files/217351056/s15010-025-02496-x.pdf}},
  doi          = {{10.1007/s15010-025-02496-x}},
  year         = {{2025}},
}