title: Emergence of resistant Klebsiella pneumoniae in the intestinal tract during successful treatment of Klebsiella pneumoniae lung infection in rats.
abstract: Antibiotic treatment of lung infections may lead to the emergence of resistance in the gut flora. Appropriate dosing regimens could mitigate this adverse effect. In gnotobiotic rats harboring intestinal Escherichia coli and Enterococcus faecium populations, a lung infection by Klebsiella pneumoniae was instigated with two different sizes of inoculum to represent an early or a late initiation of antibiotic treatment. The rats were treated with marbofloxacin, an expanded-spectrum fluoroquinolone, by a single-shot administration or a fractionated regimen over 4 days. Intestinal bacterial populations were monitored during and after treatment. At the infection site, bacterial cure without any selection of resistance was observed. Whatever the dosage regimen, fluoroquinolone treatment had a transient negative impact on the E. coli gut population but not on that of E. faecium. The intestinal flora was colonized by the pathogenic lung bacteria, and there was the emergence of intestine-resistant K. pneumoniae, occurring more often in animals treated with a single marbofloxacin dose than with the fractionated dose. Bacterial cure without resistance selection at the infection site with fluoroquinolone treatment can be linked to colonization of the digestive tract by targeted pulmonary bacteria, followed by the emergence of resistance.
authors.affiliation: UMR181 Physiopathologie et Toxicologie Expérimentales, INRA, ENVT, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, BP 87 614, 31076 Toulouse Cedex 3, France.
authors.forename: Anne-Sylvie
authors.initials: AS
authors.lastname: Kesteman
authors.forename: Agnès
authors.initials: A
authors.lastname: Perrin-Guyomard
authors.forename: Michel
authors.initials: M
authors.lastname: Laurentie
authors.forename: Pascal
authors.initials: P
authors.lastname: Sanders
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Toutain
authors.forename: Alain
authors.initials: A
authors.lastname: Bousquet-Mélou
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D016984:Enterococcus faecium / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D024841:Fluoroquinolones / Q000494:pharmacology / Q000627:therapeutic use; D007422:Intestines / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D008171:Lung Diseases / Q000188:drug therapy* / Q000382:microbiology*; D008297:Male; D051381:Rats
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C080260:marbofloxacin
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