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Multidrug-Resistant Enterobacterales Colonizing Swiss Embassy Employees and Relatives Worldwide: Molecular Features, Metagenomics, and Transmission to the Householders at Return

English title Multidrug-Resistant Enterobacterales Colonizing Swiss Embassy Employees and Relatives Worldwide: Molecular Features, Metagenomics, and Transmission to the Householders at Return
Applicant Endimiani Andrea
Number 192514
Funding scheme Project funding (Div. I-III)
Research institution Institut für Infektionskrankheiten Universität Bern
Institution of higher education University of Berne - BE
Main discipline Medical Microbiology
Start/End 01.03.2021 - 28.02.2025
Approved amount 671'414.00
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All Disciplines (5)

Discipline
Medical Microbiology
Experimental Microbiology
Methods of Epidemiology and Preventive Medicine
Infectious Diseases
Molecular Biology

Keywords (25)

Surveillance; Carbapenemases; Household; Community; Enterobacteriaceae; KPC; Whole-genome sequencing; Plasmid; E. coli; MDR; Transmission; Gut; Global; Surveillance; ESBL; Colonization; Intestinal; Stools; CTX-M; E. coli; multidrug-resistant; Prevalence; Colistin; Whole-plasmid sequencing; NDM

Lay Summary (Italian)

Lead
Molte persone in comunità, specialmente quelle residenti nelle nazioni a basso reddito, sono colonizzate a livello intestinale con batteri multi-resistenti agli antibiotici. Tali "super batteri" possono essere trasmessi da un individuo all'altro, incrementando il rischio di sviluppare infezioni difficilmente trattabili. In questo progetto studieremo la diffusione dei "super batteri" fra i dipendenti delle ambasciate svizzere e dei loro parenti (inclusi quelli residenti in Svizzera). I nostri risultati consentiranno di stabilire nuove strategie per contrastare questi batteri.
Lay summary

La prevalenza dei batteri multi-resistenti agli antibiotici ed inclusi nell'ordine degli Enterobacterales ha raggiunto livelli drammatici, rendendo il trattamento delle infezioni molto difficoltoso. È risaputo che i pazienti ospedalizzati sono spesso colonizzati a livello intestinale con questi "super batteri". Tali organismi possono essere trasmessi da un individuo all'altro, incrementando il rischio di sviluppare infezioni difficilmente trattabili. Allo stesso modo, anche le persone in comunità, specialmente quelle residenti nelle nazioni a basso reddito, possono essere colonizzate a livello intestinale con "super batteri". Tuttavia, i dati epidemiologici riguardanti questo specifico aspetto sono molto scarsi.

In questo progetto analizzeremo la prevalenza e le caratteristiche molecolari dei "super batteri" presenti nel tratto intestinale dei confederati che lavorano presso le ambasciate svizzere di tutto il mondo; anche i parenti o partener di questi soggetti saranno studiati. Inoltre, i parenti residenti in Svizzera, ed ospitanti i dipendenti delle ambasciate e le loro famiglie durante le vacanze, verranno studiati allo scopo di stabilire la possibile trasmissione di "super batteri".  

Il nostro studio ci permetterà di capire i meccanismi di trasmissione interumana dei batteri multi-resistenti agli antibiotici. Questi dati saranno essenziali per studiare le epidemie e la diffusione dei “super batteri”, soprattutto quelli emergenti nelle nazioni a basso reddito. Inoltre, la caratterizzazione molecolare dei batteri potrà fornire informazioni essenziali per lo sviluppo di nuovi test diagnostici e nuove strategie terapeutiche.

Direct link to Lay Summary Last update: 13.01.2021

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Antimicrobial-Resistant Escherichia coli Strains and Their Plasmids in People, Poultry, and Chicken Meat in Laos
Moser Aline I., Kuenzli Esther, Campos-Madueno Edgar I., Büdel Thomas, Rattanavong Sayaphet, Vongsouvath Manivanh, Hatz Christoph, Endimiani Andrea (2021), Antimicrobial-Resistant Escherichia coli Strains and Their Plasmids in People, Poultry, and Chicken Meat in Laos, in Frontiers in Microbiology, 12, 1-15.
Exploring the global spread of Klebsiella grimontii isolates possessing blaVIM-1 and mcr-9
Campos-Madueno Edgar I., Moser Aline I., Risch Martin, Bodmer Thomas, Endimiani Andrea (2021), Exploring the global spread of Klebsiella grimontii isolates possessing blaVIM-1 and mcr-9, in Antimicrobial Agents and Chemotherapy.

Collaboration

Group / person Country
Types of collaboration
Prof. Hatz and Dr. Kuenzli - Tropical Public Health Institute, Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Associated projects

Number Title Start Funding scheme
177378 Whole Genome and Plasmid Sequencing for MDR Enterobacteriaceae Simultaneously Isolated from Multiple Human and Non-Human Settings: Deciphering Impact, Risks, and Dynamics for Resistance Transmission and Spread 01.03.2018 NRP 72 Antimicrobial Resistance
170063 Extended-Spectrum Cephalosporin- and/or Colistin-Resistant Enterobacteriaceae in Swiss Travellers to Tanzania and Thailand, in the local population, in broiler chicken and in chicken meat 01.09.2017 Project funding (Div. I-III)
153377 Intestinal Carriage of Extended-Spectrum Cephalosporin-Resistant Enterobacteriaceae among People and Pets in Households: Descriptive Epidemiology and Role of Microbiota 01.09.2014 Project funding (Div. I-III)

Abstract

Background and rationaleThe rising prevalence of infections due to multidrug-resistant Enterobacterales (MDR-Ent) represents a serious concern. Hospitalized people and subjects in the community may carry such pathogens at gut level contributing to their spread. However, international travel is recognized as the major risk factor for acquiring MDR-Ent. Overall, carriers of MDR-Ent are at risk to develop difficult-to-treat infections and can transmit such pathogens to other people in contact with them (e.g., in the household, HH). People from Western countries who live for long periods in areas with high prevalence of MDR-Ent might present the same frequency of gut colonization as for travelers, thus having similar risks of infection and transmission to other subjects. However, data regarding this relevant epidemiological aspect are lacking. Moreover, while information about MDR-Ent gut colonization in people in community is available from European countries, the same aspect is scarcely explored in poorer countries. This epidemiological bias also directly generates a lack of data regarding the molecular features (e.g., sequence types; plasmids; antimicrobial resistance genes, ARGs) of MDR-Ent that are emerging in such areas and could be imported in low prevalence countries (e.g., Switzerland).Thanks to the support of the Federal Department of Foreign Affairs (FDFA), in this project we will analyze the stools of ~750 volunteers including the Swiss embassies’ employees (EEs) who work around the world at the 102 Swiss embassies and their relatives/partners (Rs/Ps). To study transmission rates and epidemiological impact for Switzerland, we will also analyze 75 hosting HHs (including local residents) where EEs return temporarily (e.g., for vacation) with their Rs/Ps. All volunteers will provide fecal samples and epidemiological questionnaires at different time points. Specific aims:Aim 1: Molecular features of MDR-Ent colonizing the intestinal tract of EEs and Rs/Ps. We will use an improved selective culture-based approach to detect the MDR-Ent in the stools of the ~750 EEs/Rs/Ps (screening 1). Overall, ~280 MDR-Ent will be phenotypically (MICs) and molecularly (whole-genome/plasmid sequencing, WGS/WPS) characterized. Aim 2: Colonization status of EEs and Rs/Ps at return and analysis of MDR-Ent transmission in the Swiss HHs. After screening 1, we will select 75 groups (including EE/Rs/Ps of which at least one is carrier of MDR-Ent) to be rescreened just before a trip to Switzerland; at the same time, the hosting householders (HHHrs) in Switzerland will be tested (screening 2). After the return of the EEs/Rs/Ps to the foreign country, stools of all subjects will be collected and analyzed again (screening 3). WGS/WPS will be performed on the ~310 MDR-Ent isolated from the stools of EEs/Rs/Ps and HHHrs obtained at screening 2 and 3.Aim 3: Metagenomic approaches to detect novel ARGs and to define the hidden resistome. Functional metagenomics will be executed on the stools of the 75 EEs obtained at screening 2. For 15 groups (out of the 75 of aim 2), shotgun metagenomics will be performed on the stools obtained from all subjects at screening 2 and 3 (~100 samples).Expected results and impact of the studyWe will explore the extent of MDR-Ent gut colonization among EEs and Rs/Ps and the factors associated with this condition. The different molecular features of MDR-Ent will be defined, therefore providing important insights regarding the clones and/or plasmids that could be imported and spread in Switzerland in the near future. We will also delineate the rate of transmission of MDR-Ent and/or plasmids from the EEs/Rs/Ps to the HHHrs. This will have key implications on the possible countermeasures that may be applied to prevent importation and transmission in the Swiss HHs. By taking into account the functional metagenomic results novel ARGs and/or mobile genetic elements (MGEs; e.g., plasmids) will be identified in cultured strains. This will help defining the natural bacterial species that harbor such genes. Finally, the shotgun metagenomic analyses will provide essential information about ARG content and abundance (hidden resistome) that cannot be obtained with the culture approaches.
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