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

NCT ID: NCT04764500

Last Updated: 2025-03-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 39 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-06-13
• Study Completion Date: 2025-12-31

Brief Summary

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.

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).

Conditions

Extended Spectrum Beta Lactamases (ESBL) E. Coli

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

travellers to Southeast Asia

Clients planning to travel to Southeast Asia will be recruited

examination of stool sample

Intervention Type: OTHER

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.

patient questionnaire

Intervention Type: OTHER

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.

examination of blood sample

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gebert Rüf-Stiftung

UNKNOWN

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adrian Egli, PD Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Division of Clinical Microbiology, University Hospital Basel

Locations

University Hospital Basel, Division of Clinical Microbiology

Basel, , Switzerland

Countries

Switzerland

Other Identifiers

2019-00044; am21Egli

Identifier Type: -

Identifier Source: org_study_id