Open Access Study protocol

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

Maris S Arcilla1, Jarne M van Hattem2, Martin CJ Bootsma34, Perry J van Genderen5, Abraham Goorhuis2, Constance Schultsz2, Ellen E Stobberingh6, Henri A Verbrugh1, Menno D de Jong2, Damian C Melles1 and John Penders67*

Author Affiliations

1 Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, the Netherlands

2 Academic Medical Center, Department of Medical Microbiology, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands

3 Julius Center for Health Research& Primary Care, University Medical Center Utrecht, Heidelberglaan 100, PO 85500, 3508 GA Utrecht, the Netherlands

4 Department of Mathematics, Faculty of Science, Utrecht University, Budapestlaan 6, PO 80010, 3584 CD Utrecht, the Netherlands

5 Department of Internal Medicine, Havenziekenhuis - Institute for Tropical Diseases, Haringvliet 2, 3011 TD Rotterdam, the Netherlands

6 Department of Medical Microbiology, School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, PO 5800, 6202 AZ Maastricht, the Netherlands

7 Department of Epidemiology, School for Public Health and Primary Care, Maastricht University, PO 616, 6200 MD Maastricht, the Netherlands

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BMC Public Health 2014, 14:410  doi:10.1186/1471-2458-14-410

Published: 28 April 2014



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.


The COMBAT-study is a large-scale multicenter longitudinal cohort study among travellers (nā€‰=ā€‰2001) and their non-travelling household members (nā€‰=ā€‰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.


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 under accession number NCT01676974.

Antimicrobial resistance; Extended-spectrum beta-lactamase; Carbapenemase; Enterobacteriaceae; Prospective cohort; Travel