Developing Microbials to Fight Extended-spectrum Beta-lactamase (ESBL)-Producing Escherichia Coli

This study is to identify and isolate well-defined microbials (non-ESBL E. coli) in an observational setting exploring natural gastrointestinal decolonization of humans colonized with ESBL E. coli.

Study Overview

• Status: Active, not recruiting
• Conditions: Extended Spectrum Beta Lactamases (ESBL) E. Coli
• Intervention / Treatment: Other: examination of stool sample; Other: patient questionnaire; Other: examination of blood sample

Detailed Description

Antibiotic resistance is a severe threat to contemporary medicine. Effective approaches to fight multi-drug resistant pathogenic bacteria are needed.

This clinical observational study is to investigate whether express extended spectrum beta lactamases (ESBL) E. coli colonizing the human gut can be out-competed by other, ideally pan-sensitive strains (non-ESBL E. coli).

• Study Type: Observational
• Enrollment (Actual): 39

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel, Division of Clinical Microbiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Clients planning to travel to Southeast Asia will be recruited while receiving pre-travel health advice at the travel clinic of the Swiss Tropical and Public Health Institute in Basel.

Description

Inclusion Criteria:

• travelling to Southeast Asia (India, Bhutan, Nepal, Bangladesh, Myanmar, Thailand, Laos, Cambodia, Vietnam) for a maximum of 4 weeks.

Exclusion Criteria:

• other travelling destinations than mentioned above
• antibiotic use at the first sampling time
• Participants who are not colonized will serve as a control group for microbiome comparison

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

travellers to Southeast Asia; Clients planning to travel to Southeast Asia will be recruited

Other: examination of stool sample; Each participant provides stool samples before and after travelling, after 2, 4, 6, 8, 10, 12, 16, 20 and 52 weeks. Stool samples will be used for isolating both a) ESBL E. coli strains and b) pan-sensitive E. coli strains. Part of the stool sample is stored for isolation of further E. coli clones and microbiota analysis of the isolation of other microbiota strains. All found Enterobacteriaceae will be screened for additional resistance such as Carbapenem and Colistin. In case of a specific resistance, this will be confirmed with additional phenotypic and genotypic tests such as ROSCO disk and polymerase chain reaction (PCR) based panel and whole genome sequencing in order to detect specific resistance mechanisms and genes. Bacteria will be sequenced using Illumina and Nanopore based sequencing. Bioinformatic analysis will allow to determine the whole bacterial genome with containing resistance genes and also describe the microbiota diversity over time in single individuals.; Other: patient questionnaire; Each participant will have to provide a questionnaire before and after travelling, as well after 2, 4, 6, 8, 10, 12, 16, 20 and 52 weeks.; Other: examination of blood sample; Each participant will have to provide a blood sample before and after travelling and after 6, 12 and 20 weeks. A serum sample (5mL) for antibody measurement and a 50 ml blood sample for recovery of peripheral blood mononuclear cells (PBMCs in 6 CPTs) for cell mediated immunity will be collected. Serum and PBMCs will allow the analysis of anti-E. coli humoral and cellular responses in order to characterize the individual immune response to specific bacteria over time. Single nucleotide polymorphisms associated with humoral and cellular immune responses will be characterized and linked to immunological and clinical phenotypes and endpoints of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of patients being "naturally" decolonized from ESBL E. coli	proportion of patients being "naturally" decolonized from ESBL E. coli at the end of the study period at 18 months	18 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Gebert Rüf-Stiftung
• Investigators: Principal Investigator: Adrian Egli, PD Dr. med., Division of Clinical Microbiology, University Hospital Basel

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2019
• Primary Completion (Actual): February 9, 2020
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: February 17, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 28, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Antibiotic resistance; pan-sensitive strains (non-ESBL E. coli); multidrug resistant E. coli strains; ESBL E. coli displacement; multidrug resistant Enterobacteriaceae
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Enterobacteriaceae Infections; Escherichia coli Infections
• Other Study ID Numbers: 2019-00044; am21Egli

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No