Dynamics of intestinal multidrug-resistant bacteria colonisation contracted by visitors to a high-endemic setting: a prospective, daily, real-time sampling study

Abstract

Summary Background Antimicrobial resistance is highly prevalent in low-income and middle-income countries. International travel contributes substantially to the global spread of intestinal multidrug-resistant Gram-negative bacteria. Hundreds of millions of annual visitors to low-income and middle-income countries are all exposed to intestinal multidrug-resistant Gram-negative bacteria resulting in 30–70% of them being colonised at their return. The colonisation process in high-exposure environments is poorly documented because data have only been derived from before travel and after travel sampling. We characterised colonisation dynamics by exploring daily stool samples while visiting a low-income and middle-income countries. Methods In this prospective, daily, real-time sampling study 20 European visitors to Laos volunteered to provide daily stool samples and completed daily questionnaires for 22 days. Samples were initially assessed at Mahosot Hospital, Vientiane, Laos, for acquisition of extended-spectrum β-lactamase-producing (ESBL) Gram-negative bacteria followed by whole-genome sequencing of isolates at MicrobesNG, University of Birmingham, Birmingham, UK. The primary outcome of the study was to obtain data on the dynamics of intestinal multidrug-resistant bacteria acquisition. Findings Between Sept 18 and Sept 20, 2015, 23 volunteers were recruited, of whom 20 (87%) European volunteers were included in the final study population. Although colonisation rates were 70% at the end of the study, daily sampling revealed that all participants had acquired ESBL-producing Gram-negative bacteria at some point during the study period; the colonisation status varied day by day. Whole-genome sequencing analysis ascribed the transient pattern of colonisation to sequential acquisition of new strains, resulting in a loss of detectable colonisation by the initial multidrug-resistant Gram-negative strains. 19 (95%) participants acquired two to seven strains. Of the 83 unique strains identified (53 Escherichia coli , 10 Klebsiella spp, and 20 other ESBL-producing Gram-negative bacteria), some were shared by as many as four (20%) participants. Interpretation To our knowledge, this is the first study to characterise in real-time the dynamics of acquiring multidrug-resistant Gram-negative bacterial colonisation during travel. Our data show multiple transient colonisation events indicative of constant microbial competition and suggest that travellers are exposed to a greater burden of multidrug-resistant bacteria than previously thought. The data emphasise the need for preventing travellers' diarrhoea and limiting antibiotic use, addressing the two major factors predisposing colonisation. Funding The Finnish Governmental Subsidy for Health Science Research, The Scandinavian Society for Antimicrobial Chemotherapy, the Sigrid Jusélius F...

Interplay between bacterial clone and plasmid in the spread of antibiotic resistance genes in the gut: lessons from a temporal study in veal calves

“…3), which highlights that ESBL carriage in veal farms is a highly dynamic process. These data extend similar observations from our group and others on ESBL clones colonizing the human microbiota, for instance where multiple transient colonizations by up to seven E. coli clones was also found to drive the intestinal carriage of bla CTX-M genes over a 22-days period (66) in humans visiting high-risk areas for acquiring ESBL-producers (67). Such similar data on intestinal dynamics in ESBL colonization is noticeable considering the differences in gut microbiota composition between humans and cattle at inter-species level (68–70) and intra-species level (71, 72).…”

Antimicrobial-resistant bacteria in international travelers

“…Antimicrobial usage, travelers’ diarrhea and destination have been repeatedly identified as risk factors for AMR bacterial acquisition during travel (Fig. 1 ) [ 22 ▪ , 26 , 29 ▪ , 37 ▪▪ , 41 ▪▪ , 45 ▪ ].…”

“…A study of 20 European travelers to Laos in 2015 found that 70% of participants were colonized at the end of the study. All participants had at least transiently acquired ESBL-PE, the majority of which were E. coli , and 28% of isolates had plasmid-mediated colistin resistance [ 45 ▪ ]. Further evidence suggests that travel to Africa (other than Southern Africa) and South Asia increased risk of CTX-M group 1 acquisition; there appears to be a regional association with specific CTX genes encoding ESBL's [ 29 ▪ ].…”

Reisediarrhö

“…Im Vordergrund stehen dabei Enterobakterien, die durch den Erwerb und die Verbreitung von Beta-Laktamasen mit erweitertem Spektrum ("extended spectrum betalactamase", ESBL), die Resistenzen gegen die meisten Betalaktam-Antibiotika verleihen, zunehmend unempfindlich gegen Erstlinien-Antibiotika geworden sind [19]. Eine rezente Echtzeitcharakterisierung der Dynamik der Besiedlung mit MRGN während der Reise deutet auf sequenzielle vorübergehende Kolonisationsereignisse hin, die eine ständige mikrobielle Konkurrenz beinhaltet und nahelegt, dass Reisende einer größeren Belastung durch MRGN ausgesetzt sind als bislang angenommen [20]. Diese Daten unterstreichen die Notwendigkeit, einer Reisediarrhö vorzubeugen und den Einsatz von Antibiotika zu begrenzen, wodurch die beiden Hauptfaktoren, die für eine intestinale MRGN-Kolonisation prädisponieren, adressiert werden.…”