Genomic and Phenotypic Diversity of Carbapenemase-producing Escherichia Coli Strains Circulating in Southern France

NCT07676513 | Not Yet Recruiting

• 1 other identifier: NIMAO/2025-2/AP-01
• Study Type: observational
• Target: 163
• Locations: 1 country
• Sites: 1

Brief Summary

Carbapenemase-producing Enterobacteriaceae (CPE) are classified as emerging Highly Resistant Bacteria (eHRB) because they expose infected patients to the risk of treatment failure due to the strains' resistance to last-line β-lactams, carbapenems, and frequent co-resistance to other classes of antibiotics, leading to increased morbidity and mortality. Their high epidemiogenic potential has enabled their global spread. In France, the incidence of Carbapenemase-producing Enterobacteriaceae is rising sharply, both in colonization and in infections. Parallel to this increase, Escherichia coli has become the most common Carbapenemase-producing Enterobacteriaceae (35% of strains in 2024, National Research Committee data), surpassing Klebsiella pneumoniae (24%). The investigators hypothesize that the increase in the prevalence of carbapenemase-producing Echerichia coli is associated with a diversification of clones, enzymes, and their variants, and may pose a threefold threat: i) the spread of genes encoding carbapenemases within pathogenic extraintestinal Echerichia coli (ExPEC) pathogroups responsible for urinary tract infections and bacteremias, with a high risk of resistance spreading in the community, ii) the silent spread of Echerichia coli strains producing OXA-48 variants with reduced carbapenem hydrolytic activity, OXA-244 and OXA-484, which are not detected or poorly detected by conventionally used screening media and iii) the emergence of New Dehli Metallo-beta-lactamase (NDM) variants with high hydrolytic activity, such as NDM-5, within Echerichia coli clones possessing Penicillin-Binding Proteins (PLPs) with low affinity for antibiotics, leading to very high-level resistance and a therapeutic dead end in infected patients.

Conditions

Antibiotic Resistance; Enterobacteriaceae Infections; Carbapenem-Resistant Enterobacteriaceae Infection; Colonization

Keywords

Escherichia coli; Carbapenem-Resistant Enterobacteriaceae Infection; Colonization; Enterobacteriaceae Infections

Outcome Measures

Primary Outcomes (2)

• Genetic diversity of carbapenemase-producing E. coli strains from the Reference Laboratory for Medical Biology for Emerging Highly Resistant Bacteria

  Typing via whole-genome sequencing of bacterial genomes and analysis using whole-genome MultiLocus Sequence Typing (wgMLST) to characterize the molecular epidemiology and identify high-risk clones circulating in southern France

  2 years

• Assessment of the content of antibiotic resistance genes (resistome), virulence genes (virulome), and plasmids (percentage of presence).

  Resistome, virulome and plasmids will be measured as percentages in each strain identified.

  2 years

Secondary Outcomes (19)

• Antibiotic resistance phenotype:

  2 years

• Study of bacterial growth curves for the main identified clones

  2 years

• Study of biofilm formation (Bioflux 200TM system) for the main identified clones,

  2 years

• Study of bacterial motility (swimming, swarming) for the main identified clones

  2 years

• Performance of eHRB screening media on carbapenemase-producing E. coli strains

  2 years

Interventions

MultiLocus Sequence Typing GENETIC

Study of the genetic diversity of carbapenemase-producing E. coli strains from the Reference Laboratory for Medical Biology (LBMR) for Emerging Highly Resistant Bacteria (eHRB) via whole-genome sequencing of bacterial genomes and analysis using whole-genome MultiLocus Sequence Typing (wgMLST) to characterize the molecular epidemiology and identify high-risk clones circulating in southern France and assessment of the content of antibiotic resistance genes (resistome), virulence genes (virulome), and plasmids (percentage of presence).

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This translational research study involves the analysis of samples from an existing multicenter cohort: the strain bank of the Reference Laboratory for Medical Biology (LBMR) for Emerging Highly Resistant Bacteria (eHRB). It is a collection of 163 carbapenemase-producing E. coli strains collected at the Microbiology Laboratory between 2023 and 2024. The panel of E. coli strains isolated from various infections and colonization sites will be selected following genomic characterization to ensure it is as representative as possible of the predominant clones identified. The selected strains will then be phenotypically characterized through further analyses.

You may qualify if:

• Not applicable to this study of an existing collection of Carbapenemase-producing Enterobacteriaceae strains.

You may not qualify if:

• Not applicable to this study of an existing collection of Carbapenemase-producing Enterobacteriaceae strains.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (1)

Nîmes University Hospital

Nîmes, Gard, 30029, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

In 2011, the Microbiology and Hospital Hygiene Laboratory at the Nîmes University Hospital was designated as the regional center of expertise for BHRe by the Regional Health Agency; then, in 2021, it became the Reference Medical Biology Laboratory (LBMR) for EHRB. Between 2023 and 2024, a total of 479 CPE strains were isolated or sent to the laboratory for analysis, representing a 45% increase compared to the 2021-2022 period (Table 1). Of these strains, 163 were E. coli (vs. 71 between 2021 and 2022, +130%). Furthermore, the number of carbapenemase-producing E. coli strains from diagnostic samples increased very sharply (+231%) during the 2023-2024 period (n=86), compared to 2021-2022 (n=26). These samples came from hospital laboratories (n=64) and private clinics (n=51), as well as community laboratories (n=48).

MeSH Terms

Conditions

Enterobacteriaceae Infections; Escherichia coli Infections

Interventions

Multilocus Sequence Typing

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Molecular Typing; Bacterial Typing Techniques; Bacteriological Techniques; Microbiological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Sequence Analysis, DNA; Sequence Analysis

Central Study Contacts

Alix PANTEL, Dr.

CONTACT

+334.66.68.32.02; alix.pantel@chu-nimes.fr

Anissa MEGZARI

CONTACT

0466684236; drc@chu-nimes.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2026
• First Posted: June 30, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: July 8, 2026

Record last verified: 2026-07

Locations

FR (1)