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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Ampicillin / administration & dosage
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Ampicillin / pharmacokinetics
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Ampicillin / pharmacology*
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Ampicillin Resistance / genetics
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Ampicillin Resistance / physiology*
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Animals
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Digestive System / drug effects
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Digestive System / microbiology*
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Dogs
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Escherichia coli / drug effects
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Escherichia coli / enzymology
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Feces / microbiology
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Infusions, Parenteral
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Jejunum / microbiology
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Male
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Penicillins / administration & dosage
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Penicillins / pharmacokinetics
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Penicillins / pharmacology*
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Recombinant Proteins / pharmacology
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Tablets, Enteric-Coated
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beta-Lactamases / administration & dosage
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beta-Lactamases / genetics
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beta-Lactamases / pharmacology*
Substances
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Penicillins
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Recombinant Proteins
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Tablets, Enteric-Coated
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Ampicillin
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beta-Lactamases