Orally administered targeted recombinant Beta-lactamase prevents ampicillin-induced selective pressure on the gut microbiota: a novel approach to reducing antimicrobial resistance.
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.
Harmoinen
Jaana
J
Faculty of Veterinary Medicine, Department of Clinical Veterinary Sciences, 00014-University of Helsinki, Helsinki, Finland. jaana.harmoinen@helsinki.fi
Mentula
Silja
S
Heikkilä
Matti
M
van der Rest
Michel
M
Rajala-Schultz
Päivi J
PJ
Donskey
Curtis J
CJ
Frias
Rafael
R
Koski
Pertti
P
Wickstrand
Nina
N
Jousimies-Somer
Hannele
H
Westermarck
Elias
E
Lindevall
Kai
K
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*
D010406:Penicillins; D011994:Recombinant Proteins; D013608:Tablets, Enteric-Coated; D000667:Ampicillin; D001618:beta-Lactamases