title: Orally administered targeted recombinant Beta-lactamase prevents ampicillin-induced selective pressure on the gut microbiota: a novel approach to reducing antimicrobial resistance.
abstract: Antibiotics that are excreted into the intestinal tract promote antibiotic resistance by exerting selective pressure on the gut microbiota. Using a beagle dog model, we show that an orally administered targeted recombinant beta-lactamase enzyme eliminates the portion of parenteral ampicillin that is excreted into the small intestine, preventing ampicillin-induced changes to the fecal microbiota without affecting ampicillin levels in serum. In dogs receiving ampicillin, significant disruption of the fecal microbiota and the emergence of ampicillin-resistant Escherichia coli and TEM genes were observed, whereas in dogs treated with ampicillin in combination with an oral beta-lactamase, these did not occur. These results suggest a new strategy for reducing antimicrobial resistance in humans.
authors.affiliation: Faculty of Veterinary Medicine, Department of Clinical Veterinary Sciences, 00014-University of Helsinki, Helsinki, Finland. jaana.harmoinen@helsinki.fi
authors.forename: Jaana
authors.initials: J
authors.lastname: Harmoinen
authors.forename: Silja
authors.initials: S
authors.lastname: Mentula
authors.forename: Matti
authors.initials: M
authors.lastname: Heikkilä
authors.forename: Michel
authors.initials: M
authors.lastname: van der Rest
authors.forename: Päivi J
authors.initials: PJ
authors.lastname: Rajala-Schultz
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Donskey
authors.forename: Rafael
authors.initials: R
authors.lastname: Frias
authors.forename: Pertti
authors.initials: P
authors.lastname: Koski
authors.forename: Nina
authors.initials: N
authors.lastname: Wickstrand
authors.forename: Hannele
authors.initials: H
authors.lastname: Jousimies-Somer
authors.forename: Elias
authors.initials: E
authors.lastname: Westermarck
authors.forename: Kai
authors.initials: K
authors.lastname: Lindevall
mesh_terms: D000284:Administration, Oral; D000667:Ampicillin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000668:Ampicillin Resistance / Q000235:genetics / Q000502:physiology*; D000818:Animals; D004064:Digestive System / Q000187:drug effects / Q000382:microbiology*; D004285:Dogs; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D005243:Feces / Q000382:microbiology; D007263:Infusions, Parenteral; D007583:Jejunum / Q000382:microbiology; D008297:Male; D010406:Penicillins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013608:Tablets, Enteric-Coated; D001618:beta-Lactamases / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*
chemical_list: D010406:Penicillins; D011994:Recombinant Proteins; D013608:Tablets, Enteric-Coated; D000667:Ampicillin; D001618:beta-Lactamases