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

Clin Infect Dis. 2024 May 15;78(5):1103-1110. 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. 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.

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

Publication types

  • Observational Study
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Bacteremia* / drug therapy
  • Bacteremia* / microbiology
  • Carbapenems* / pharmacology
  • Carbapenems* / therapeutic use
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / enzymology
  • Enterobacteriaceae / genetics
  • Enterobacteriaceae Infections* / drug therapy
  • Enterobacteriaceae Infections* / microbiology
  • Enterobacteriaceae Infections* / mortality
  • Female
  • Humans
  • Male
  • Microbial Sensitivity Tests*
  • Middle Aged
  • Whole Genome Sequencing
  • beta-Lactamases* / genetics
  • beta-Lactamases* / metabolism