An observational study in Antibiotic Resistance, Enterobacteriaceae Infections and Carbapenem-Resistant Enterobacteriaceae Infection, sponsored by Centre Hospitalier Universitaire de Nīmes. Not yet recruiting at 1 site in France. Per ClinicalTrials.gov, last updated 2026-07-08.
Sponsored by Centre Hospitalier Universitaire de Nīmes · Observational
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.
Predicted to become the leading cause of death worldwide by 2050, antibiotic resistance poses a major global challenge. In France, the "2022-2025 National Strategy" led by the Ministry of Solidarity and Health combines the promotion of appropriate antibiotic use with preventive measures to control infections involving multi- and highly resistant bacteria, both in the community and in healthcare facilities.
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 species (35% of strains in 2024 National Research Committee data), surpassing Klebsiella pneumoniae (24%).
In 2011, the Microbiology and Hospital Hygiene Laboratory at Nîmes University Hospital was designated an expert center for emerging Highly Resistant Bacteria, and then, in 2021, a Reference Medical Biology Laboratory for emerging Highly Resistant Bacteria. 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. Of these strains, 163 were Echerichia coli (vs. 71 between 2021 and 2022, +130%). Furthermore, the number of carbapenemase-producing Echerichia 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 and private clinics, as well as community laboratories. The potential for community spread of highly antibiotic-resistant and virulent strains raises concerns about an epidemic outbreak following the same pattern as that of CTX-M extended-spectrum beta-lactamase (ESBL)-producing Echerichia coli in the 2000s. Screening for CPE colonization and adherence to strict additional hygiene precautions in cases of carriage are the means of combating cross-transmission of these strains in healthcare facilities. These preventive measures are not applicable in the community setting.
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.
59 studies on the registry are indexed under Enterobacteriaceae Infections; 14 are open to participants now.
This study's planned enrollment of 163 is below the median of 300 across 30 observational studies indexed under Enterobacteriaceae Infections.
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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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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).
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
Time frame: 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.
Time frame: 2 years
Antibiotic resistance phenotype:
Antibiotic susceptibility testing on Mueller-Hinton agar plates with determination of Minimum Inhibitory Concentrations (MICs) of last-line antibiotics in liquid Mueller-Hinton medium
Time frame: 2 years
Study of bacterial growth curves for the main identified clones
Growth curves will be compared using the Gompertz nonlinear regression model with GraphPad Prism 9.2 software (San Diego, CA, USA).
Time frame: 2 years
Study of biofilm formation (Bioflux 200TM system) for the main identified clones,
The Bioflux 200TM system will be used to study biofilm formation
Time frame: 2 years
Study of bacterial motility (swimming, swarming) for the main identified clones
The motility of the different bacterial strains will be assessed by comparing the average migration diameters for swimming and swarming. The experiments will be conducted independently three times.
Time frame: 2 years
Performance of eHRB screening media on carbapenemase-producing E. coli strains
Performance of the chromID® CARBA-SMART (bioMérieux), the BrillianceTM CRE (Thermo Fisher), and mSuperCARBATM (CHROMagar) will be evaluated and compared following inoculation with a bacterial suspension of various E. coli strains.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Age
Age will be recorded in years with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Sex
The patient's sex will be recorded as M/F/non-binary with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Department of residence
The patient's department of residence will be recorded with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Medical history
The patient's medical history will be examined with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Type of infection
The type of infection will be recorded with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Comorbidities
Comorbidities will be recorded with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Length of hospital stay
The length of hospital stay will be recorded in days with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Invasive devices
The presence of invasive devices will be recorded with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Surgery
The need for surgery will be recorded with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Antibiotic exposure
Antibiotic exposure will be recorded with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Repeat hospitalizations
Repeat hospitalizations will be recorded with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Recent travel
Recent travel will be recorded with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Inter-hospital transfers
Inter-hospital transfers will be recorded with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Risk factors for infections caused by carbapenemase-producing E. coli. : Cross-transmission
Cross-transmission (patient contact) between asymptomatic carriers and individuals with an infection will be recorded with the aim of identifying possible risk factors for infections caused by carbapenemase-producing E. coli.
Time frame: 2 years
Plan to share: Undecided — Data management is handled by BESPIM (Biostatistics, Epidemiology, Public Health \& Methodological Innovations, Nîmes University Hospital). The terms and conditions for the transfer of all or part of the research database are determined by the research sponsor and are set forth in a written contract.
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This study is not yet recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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