title: Enzymic degradation of a beta-lactam antibiotic, ampicillin, in the gut: a novel treatment modality.
abstract: Antibiotics can cause severe alterations in the gut microflora and promote diarrhoea and overgrowth of pathogenic bacteria. The present study investigated the potency of targeted recombinant beta-lactamase (TRBL) to degrade a beta-lactam antibiotic in the jejunum of fistula-operated beagles. We used different peroral doses of purified beta-lactamase (PenP) of Bacillus licheniformis in enteric-coated pellets together with intravenous ampicillin. Serum and jejunal samples were collected for ampicillin and beta-lactamase analysis. A dose-response effect of TRBL on ampicillin concentrations in the jejunal samples could be observed. The highest doses applied decreased the jejunal ampicillin concentrations to undetectable levels. In the serum samples, the ampicillin concentrations were not affected by the beta-lactamase dose used. Our results indicate that it may be possible to evolve a targeted treatment to degrade beta-lactam antibiotics intestinally and, thus, decrease antibiotic-induced adverse effects on the gut microflora.
authors.affiliation: Faculty of Veterinary Medicine, Department of Clinical Veterinary Sciences, PO Box 57, Helsinki, Finland. jaana.harmoinen@helsinki.fi
authors.forename: Jaana
authors.initials: J
authors.lastname: Harmoinen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vaali
authors.forename: Pertti
authors.initials: P
authors.lastname: Koski
authors.forename: Kaisa
authors.initials: K
authors.lastname: Syrjänen
authors.forename: Outi
authors.initials: O
authors.lastname: Laitinen
authors.forename: Kai
authors.initials: K
authors.lastname: Lindevall
authors.forename: Elias
authors.initials: E
authors.lastname: Westermarck
mesh_terms: D000667:Ampicillin / Q000378:metabolism*; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004064:Digestive System / Q000201:enzymology*; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D007583:Jejunum / Q000187:drug effects / Q000382:microbiology; D010406:Penicillins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013608:Tablets, Enteric-Coated; D001618:beta-Lactamases / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D010406:Penicillins; D011994:Recombinant Proteins; D013608:Tablets, Enteric-Coated; D000667:Ampicillin; D001618:beta-Lactamases