Faculty, Staff and Student Publications

Language

English

Publication Date

7-11-2025

Journal

The Journal of Infectious Diseases

DOI

10.1093/infdis/jiae616

PMID

39667036

PMCID

PMC12247830

PubMedCentral® Posted Date

12-12-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Despite the global public health threat posed by carbapenem-resistant Enterobacter spp, clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp infections.

Methods: Hospitalized patients enrolled in the CRACKLE-2 study (ClinicalTrials.gov, NCT03646227) from 2016 to 2018 with cultures positive for carbapenemase-producing Enterobacter spp were included. Clinical and microbiologic data were collected from health records. Whole genome sequencing was performed, and the population structures of selected predominant clones were analyzed.

Results: We enrolled 136 hospitalized patients with carbapenemase-producing Enterobacter spp from 30 hospitals in 7 countries. Among the 136 isolates, 11 Enterobacter spp were identified, with most isolates belonging to E xiangfangensis (n = 81 [60%]) and E hoffmannii (n = 17 [13%]) and carrying blaKPC (n = 106 [78%]) and blaNDM (n = 12 [9%]). Clinical characteristics and outcomes were similar among patients with E xiangfangensis, E hoffmannii, or the other Enterobacter spp. Thirty-day mortality was 20%, and older age at enrollment (adjusted odds ratio, 1.42 [95% confidence interval, 1.08-1.87]) was associated with increased mortality. Sequence type (ST) 171 E xiangfangensis, ST78 E hoffmannii, and ST93 E xiangfangensis were the predominant clones, and the acquisition of fluoroquinolone resistance-associated mutations and carbapenemase-encoding plasmids contributed to their formation and global dissemination.

Conclusions: Our findings demonstrate that E xiangfangensis and E hoffmannii are common species among international carbapenemase-producing Enterobacter spp, potentially linked to the clonal spread of a few predominant clones that have acquired fluoroquinolone resistance and carbapenemase-encoding plasmids.

Keywords

Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Anti-Bacterial Agents, Bacterial Proteins, beta-Lactamases, Carbapenem-Resistant Enterobacteriaceae, Cohort Studies, Enterobacter, Enterobacteriaceae Infections, Microbial Sensitivity Tests, Molecular Epidemiology, Whole Genome Sequencing, carbapenem-resistant Enterobacter spp, E xiangfangensis, E hoffmannii, molecular epidemiology, clinical characterization

Published Open-Access

yes

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