Is Carbapenem Therapy Necessary for the Treatment of Non-CTX-M ESBL-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

doi:10.1093/cid/ciad703

Is Carbapenem Therapy Necessary for the Treatment of Non-CTX-M ESBL-Producing Enterobacterales Bloodstream Infections?

Clin Infect Dis. 2023 Nov 16:ciad703. doi: 10.1093/cid/ciad703. Online ahead of print.

Authors

Dariusz A Hareza¹, Sara E Cosgrove¹, Patricia J Simner², Anthony D Harris³, Yehudit Bergman², Rick Conzemius⁴, Emily Jacobs², Stephan Beisken⁴, Pranita D Tamma⁵

Affiliations

¹ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
³ Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁴ Ares Genetics, Vienna, Austria.
⁵ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

PMID: 37972276
DOI: 10.1093/cid/ciad703

Abstract

Background: Investigations into antibiotics for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infections (BSIs) have focused on blaCTX-M genes. Outcomes of patients with 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 was employed to ensure patients infected with non-CTX-M and CTX-M ESBL-E BSIs were similar prior to evaluation of outcomes.

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 (OR=.99, 95% CI 0.87-1.11; p=0.83) and (OR=1.10, 95% CI 0.85--1.42; p=0.47), respectively. In an exploratory analysis limited to the non-CTX-M group, 86% of the 21 patients receiving meropenem were alive on day 30; none of the 5 patients receiving piperacillin-tazobactam were alive on day 30.

Conclusions: Our findings suggest that non-CTX-M and CTX-M ESBL-producing Enterobacterales 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 patients with ESBL-E BSI, beyond just blaCTX-M genes.

Keywords: CTX-M; ESBLs; SHV; antimicrobial resistance; piperacillin-tazobactam.

Abstract

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