title: Apramycin treatment affects selection and spread of a multidrug-resistant Escherichia coli strain able to colonize the human gut in the intestinal microbiota of pigs.
abstract: The effect of apramycin treatment on transfer and selection of an Escherichia coli strain (E. coli 912) in the intestine of pigs was analyzed through an in vivo experiment. The strain was sequenced and assigned to the sequence type ST101 and serotype O11. It carried resistance genes to apramycin/gentamicin, sulphonamide, tetracycline, hygromycin B, β-lactams and streptomycin [aac(3)-IV, sul2, tet(X), aph(4), bla TEM-1 and strA/B], with all but tet(X) located on the same conjugative plasmid. Nineteen pigs were randomly allocated into two inoculation groups, one treated with apramycin (pen 2) and one non-treated (pen 3), along with a non-inoculated control group (pen 1). Two pigs of pen 2 and 3 were inoculated intragastrically with a rifampicin resistant variant of the strain. Apramycin treatment in pen 2 was initiated immediately after inoculation. Strain colonization was assessed in the feces from all pigs. E. coli 912 was shown to spread to non-inoculated pigs in both groups. The selective effect did not persist beyond 3 days post-treatment, and the strain was not detected from this time point in pen 2. We demonstrated that E. coli 912 was able to spread between pigs in the same pen irrespective of treatment, and apramycin treatment resulted in significantly higher counts compared to the non-treated group. This represents the first demonstration of how antimicrobial treatment affects spread of resistant bacteria in pig production. The use of apramycin may lead to enhanced spread of gentamicin-resistant E. coli. Since gentamicin is a first-choice drug for human bacteremia, this is of concern.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark. ahefr@sund.ku.dk.
authors.forename: Ana
authors.initials: A
authors.lastname: Herrero-Fresno
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark. caza@sund.ku.dk.
authors.forename: Camilla
authors.initials: C
authors.lastname: Zachariasen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark. txq107@alumni.ku.dk.
authors.forename: Monica Hegstad
authors.initials: MH
authors.lastname: Hansen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark. alexander_s_nielsen@hotmail.com.
authors.forename: Alexander
authors.initials: A
authors.lastname: Nielsen
authors.affiliation: WHO Collaborating Centre for Antimicrobial Resistance in Food-borne Pathogens and EU Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark. rshe@food.dtu.dk.
authors.forename: Rene S
authors.initials: RS
authors.lastname: Hendriksen
authors.affiliation: Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark. saxmose@sund.ku.dk.
authors.forename: Søren Saxmose
authors.initials: SS
authors.lastname: Nielsen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark. jeo@sund.ku.dk.
authors.forename: John Elmerdahl
authors.initials: JE
authors.lastname: Olsen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D057138:Bacterial Shedding; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000502:physiology; D004927:Escherichia coli Infections / Q000382:microbiology / Q000635:transmission / Q000662:veterinary; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008297:Male; D009328:Nebramycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012641:Selection, Genetic; D013552:Swine; D013553:Swine Diseases / Q000382:microbiology*; D013997:Time Factors; D015047:Zoonoses
chemical_list: D000900:Anti-Bacterial Agents; D009328:Nebramycin; C011666:apramycin