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Time to Effective Antibiotic Therapy and Clinical Outcomes in Bloodstream Infections with ESBL-Producing Enterobacterales: A Retrospective Multicenter Cohort Study

Sahlström Månsson, Thomas LU orcid ; Askemyr, Alice LU orcid and Mellhammar, Lisa LU orcid (2026) In Open Forum Infectious Diseases
Abstract
Background
Patients with bloodstream infections with antimicrobial resistant bacteria often receive ineffective empirical therapy. The implications are still uncertain.

Methods
We performed a retrospective, multicenter, study of patients with bloodstream infections caused by Extended-Spectrum Beta-Lactamase-producing gram-negative bacteria in southern Sweden from 2013 to 2022. Patients were categorized based on time to effective therapy: ≤24 h (effective empirical therapy) and >24 h (ineffective empirical therapy). Therapy was considered effective if the agent was active in susceptibility testing and administered intravenously at an appropriate dose.

The primary outcome was 30-day mortality. Secondary... (More)
Background
Patients with bloodstream infections with antimicrobial resistant bacteria often receive ineffective empirical therapy. The implications are still uncertain.

Methods
We performed a retrospective, multicenter, study of patients with bloodstream infections caused by Extended-Spectrum Beta-Lactamase-producing gram-negative bacteria in southern Sweden from 2013 to 2022. Patients were categorized based on time to effective therapy: ≤24 h (effective empirical therapy) and >24 h (ineffective empirical therapy). Therapy was considered effective if the agent was active in susceptibility testing and administered intravenously at an appropriate dose.

The primary outcome was 30-day mortality. Secondary outcomes were ICU admission and hospital length of stay.

Results
A total of 289/644 (44.9%) patients received ineffective empirical therapy within the first 24 hours after the index blood culture collection. No significant impact of ineffective empirical therapy on 30-day mortality was found in univariable (Hazard ratio 0.66; P=0.15) or multivariable Cox regression analysis (Hazard ratio 0.64; P=0.13). Patients receiving effective empirical therapy were more likely to receive intensive care (Odds ratio 0.38; P=0.008), but the association was non-significant after adjusting for severity of illness and comorbidities.

Ineffective empirical therapy was not associated with a longer hospital stay in Fine–Gray competing risks regression analysis (univariable: sHR 1.15; P=0.082; multivariable: sHR 1.11; P=0.20).

Conclusion
Ineffective empirical therapy was not associated with 30-day mortality, in patients with bloodstream infections with Extended-Spectrum Beta-Lactamase-producing Enterobacterales. If confirmed in prospective studies, our findings could support antimicrobial stewardship efforts by reducing unnecessary empirical carbapenem use without compromising short-term clinical outcomes, particularly in low-prevalence settings (Less)
Please use this url to cite or link to this publication:
author
; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Open Forum Infectious Diseases
publisher
Oxford University Press
ISSN
2328-8957
DOI
10.1093/ofid/ofag604
language
English
LU publication?
yes
id
b96aa665-4ca1-40ce-b4ca-afec69d5a4a3
date added to LUP
2026-09-27 14:43:17
date last changed
2026-09-28 07:29:27
@article{b96aa665-4ca1-40ce-b4ca-afec69d5a4a3,
  abstract     = {{Background<br/>Patients with bloodstream infections with antimicrobial resistant bacteria often receive ineffective empirical therapy. The implications are still uncertain.<br/><br/>Methods<br/>We performed a retrospective, multicenter, study of patients with bloodstream infections caused by Extended-Spectrum Beta-Lactamase-producing gram-negative bacteria in southern Sweden from 2013 to 2022. Patients were categorized based on time to effective therapy: ≤24 h (effective empirical therapy) and &amp;gt;24 h (ineffective empirical therapy). Therapy was considered effective if the agent was active in susceptibility testing and administered intravenously at an appropriate dose.<br/><br/>The primary outcome was 30-day mortality. Secondary outcomes were ICU admission and hospital length of stay.<br/><br/>Results<br/>A total of 289/644 (44.9%) patients received ineffective empirical therapy within the first 24 hours after the index blood culture collection. No significant impact of ineffective empirical therapy on 30-day mortality was found in univariable (Hazard ratio 0.66; P=0.15) or multivariable Cox regression analysis (Hazard ratio 0.64; P=0.13). Patients receiving effective empirical therapy were more likely to receive intensive care (Odds ratio 0.38; P=0.008), but the association was non-significant after adjusting for severity of illness and comorbidities.<br/><br/>Ineffective empirical therapy was not associated with a longer hospital stay in Fine–Gray competing risks regression analysis (univariable: sHR 1.15; P=0.082; multivariable: sHR 1.11; P=0.20).<br/><br/>Conclusion<br/>Ineffective empirical therapy was not associated with 30-day mortality, in patients with bloodstream infections with Extended-Spectrum Beta-Lactamase-producing Enterobacterales. If confirmed in prospective studies, our findings could support antimicrobial stewardship efforts by reducing unnecessary empirical carbapenem use without compromising short-term clinical outcomes, particularly in low-prevalence settings}},
  author       = {{Sahlström Månsson, Thomas and Askemyr, Alice and Mellhammar, Lisa}},
  issn         = {{2328-8957}},
  language     = {{eng}},
  month        = {{09}},
  publisher    = {{Oxford University Press}},
  series       = {{Open Forum Infectious Diseases}},
  title        = {{Time to Effective Antibiotic Therapy and Clinical Outcomes in Bloodstream Infections with ESBL-Producing Enterobacterales: A Retrospective Multicenter Cohort Study}},
  url          = {{http://dx.doi.org/10.1093/ofid/ofag604}},
  doi          = {{10.1093/ofid/ofag604}},
  year         = {{2026}},
}