title: Impact of residual and therapeutic doses of ciprofloxacin in the human-flora-associated mice model.
abstract: A study was conducted to evaluate the effects of therapeutic and residual doses of ciprofloxacin on the human intestinal flora implanted into germ-free mice. Ciprofloxacin was administered daily via drinking water at concentrations to provide doses of 0, 0.125, 1.25, and 12.5mg/kg b.w. Changes in the intestinal flora composition, alteration in bacterial enzyme activities, fecal short chain fatty acid concentration and bacterial cellular fatty acid profiles, overgrowth of resistant bacteria, and disruption of the colonization barrier were the endpoints evaluated in the feces of human-flora-associated (HFA) mice. Ciprofloxacin at all tested doses decreased significantly the aerobic populations and particularly the population of Enterobacteriaceae. Selection of resistant Bacteroides fragilis group was noticed in HFA mice receiving 12.5mg/kg b.w. In mice challenged with a Salmonella strain, exogenous Salmonella persisted in the feces of all treated mice indicating that the flora responsible for the colonization barrier effect was disturbed by the antibiotic treatment. None of the studied metabolic parameters of the flora were affected by ciprofloxacin at any dose level. Under the experimental conditions of the study, the no-observed-effect level of ciprofloxacin was found to be less than 0.125 mg/kg b.w.
authors.affiliation: Agence Française de Sécurité Sanitaire des Aliments, Laboratoire d'études et de Recherches sur les Médicaments Vétérinaires et les Désinfectants, BP 90203, 35302 Fougères cedex, France. a.perrin-guyomard@afssa.fr
authors.forename: Agnes
authors.initials: A
authors.lastname: Perrin-Guyomard
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Poul
authors.forename: Denis E
authors.initials: DE
authors.lastname: Corpet
authors.forename: Pascal
authors.initials: P
authors.lastname: Sanders
authors.forename: A Haydée
authors.initials: AH
authors.lastname: Fernández
authors.forename: Mary
authors.initials: M
authors.lastname: Bartholomew
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D001421:Bacteria, Anaerobic / Q000187:drug effects / Q000254:growth & development; D001424:Bacterial Infections / Q000188:drug therapy / Q000378:metabolism; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004350:Drug Residues / Q000378:metabolism; D004755:Enterobacteriaceae / Q000187:drug effects / Q000254:growth & development; D016983:Enterococcus / Q000187:drug effects / Q000254:growth & development; D005232:Fatty Acids, Volatile / Q000145:classification / Q000378:metabolism; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology; D051379:Mice; D009565:Nitrate Reductases / Q000378:metabolism; D009601:Nitroreductases / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D001617:beta-Glucosidase / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D005232:Fatty Acids, Volatile; D002939:Ciprofloxacin; D009565:Nitrate Reductases; D009601:Nitroreductases; D001617:beta-Glucosidase; D005966:Glucuronidase