Is Carbapenem Therapy Necessary for the Treatment of Non-CTX-M Extended-Spectrum β-Lactamase-Producing Enterobacterales Bloodstream Infections?

Dariusz A. Hareza, Sara E. Cosgrove, Patricia J. Simner, Anthony D. Harris, Yehudit Bergman, Rick Conzemius, Emily Jacobs, Stephan Beisken, Pranita D. Tamma

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Investigations into antibiotics for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infections (BSIs) have focused on blaCTX-M genes. Patient outcomes from non-CTX-M-producing ESBL-E BSIs and optimal treatment are unknown. METHODS: A multicenter observational study investigating 500 consecutive patients with ceftriaxone-resistant Enterobacterales BSIs during 2018-2022 was conducted. Broth microdilution and whole-genome sequencing confirmed antibiotic susceptibilities and ESBL gene presence, respectively. Inverse probability weighting (IPW) using propensity scores ensured patients with non-CTX-M and CTX-M ESBL-E BSIs were similar before outcome evaluation. RESULTS: 396 patients (79.2%) were confirmed to have an ESBL-E BSI. ESBL gene family prevalence was as follows: blaCTX-M (n = 370), blaSHV (n = 16), blaOXY (n = 12), and blaVEB (n = 5). ESBL gene identification was not limited to Escherichia coli and Klebsiella species. In the IPW cohort, there was no difference in 30-day mortality or ESBL-E infection recurrence between the non-CTX-M and CTX-M groups (odds ratio [OR], 0.99; 95% confidence interval [CI], .87-1.11; P = .83 and OR, 1.10; 95% CI, .85-1.42; P = .47, respectively). In an exploratory analysis limited to the non-CTX-M group, 86% of the 21 patients who received meropenem were alive on day 30; none of the 5 patients who received piperacillin-tazobactam were alive on day 30. CONCLUSIONS: Our findings suggest that non-CTX-M and CTX-M ESBL-E BSIs are equally concerning and associated with similar clinical outcomes. Meropenem may be associated with improved survival in patients with non-CTX-M ESBL-E BSIs, underscoring the potential benefit of comprehensive molecular diagnostics to enable early antibiotic optimization for ESBL-E BSIs beyond just blaCTX-M genes.

Original languageAmerican English
Pages (from-to)1103-1110
Number of pages8
JournalClinical Infectious Diseases
Issue number5
StatePublished - 15 May 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [email protected].


  • CTX-M
  • ESBLs
  • SHV
  • antimicrobial resistance
  • piperacillin-tazobactam


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