The Carriage Of Multiresistant Bacteria After Travel (COMBAT) prospective cohort study: methodology and design

Abstract

Background: Antimicrobial resistance (AMR) is one of the major threats to public health around the world. Besides the intense use and misuse of antimicrobial agents as the major force behind the increase in antimicrobial resistance, the exponential increase of international travel may also substantially contribute to the emergence and spread of AMR. However, knowledge on the extent to which international travel contributes to this is still limited. The Carriage Of Multiresistant Bacteria After Travel (COMBAT) study aims to 1. determine the acquisition rate of multiresistant Enterobacteriaceae during foreign travel 2. ascertain the duration of carriage of these micro-organisms 3. determine the transmission rate within households 4. identify risk factors for acquisition, persistence of carriage and transmission of multiresistant Enterobacteriaceae.

Methods/design: The COMBAT-study is a large-scale multicenter longitudinal cohort study among travellers (n = 2001) and their non-travelling household members (n = 215). Faecal samples are collected before and immediately after travel and 1 month after return from all participants. Follow-up faecal samples are collected 3, 6 and 12 months after return from travellers (and their non-travelling household members) who acquired multiresistant Enterobacteriaceae. Questionnaires are collected from all participants at each time-point. Faecal samples are screened phenotypically for the presence of extended-spectrum beta-lactamase (ESBL) or carbapenemase-producing Enterobacteriaceae. Positive post-travel isolates from travellers with negative pre-travel samples are genotypically analysed for ESBL and carbapenemase genes with microarray and gene sequencing.

Discussion: The design and scale of the COMBAT-study will enable us to provide much needed detailed insights into the risks and dynamics of introduction and spread of ESBL- and carbapenemase-producing Enterobacteriaceae by healthy travellers and the potential need and measures to monitor or manage these risks.

Trial registration: The study is registered at clinicaltrials.gov under accession number NCT01676974.

Figure 1

Flowchart of study design. * Depending on colonization status of traveller (or his/her household member) at previous time-points.

Figure 2

Geographic distribution of residences of participating travellers (n = 2001) throughout the Netherlands according to study center. i. Yellow circles represent participants from Tropencentrum AMC, Amsterdam. ii. Red circles represent participants from Travel Clinic Havenziekenhuis, Rotterdam. iii. Blue circles represent participants from Maastricht University Medical Center, Maastricht.

Figure 3

Heatmap showing the countries visited by the participating travellers (n = 2001). i. Grey color indicates 0–1 travellers visited country. ii. Light yellow color indicates 2–10 travellers visited country. iii. Orange color indicates 11–51 travellers visited country. iv. Light brown color indicates 50–100 travellers visited country. v. Dark brown color indicates > 100 travellers visited country.