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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Extended Spectrum Beta Lactamases (ESBL) E. Coli

Intervention / Treatment
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* Other: examination of stool sample
* Other: patient questionnaire
* Other: examination of blood sample


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| travellers to Southeast Asia<br>Clients planning to travel to Southeast Asia will be recruited | Other: examination of stool sample<br>* 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.<br>Other: patient questionnaire<br>* 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.<br>Other: examination of blood sample<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibiotic resistance, pan-sensitive strains (non-ESBL E. coli), multidrug resistant E. coli strains, ESBL E. coli displacement, multidrug resistant Enterobacteriaceae