title: Therapeutic efficacy of fleroxacin for eliminating catheter-associated urinary tract infection in a rabbit model.
abstract: The efficacy of fleroxacin as therapy for experimentally induced catheter-associated urinary tract infection (CAUTI) was examined. A rabbit model of CAUTI using a closed urinary catheter drainage system and the mutant strain of Escherichia coli (WE 6933) were used to examine three dosage regimens (30 mg/kg q8h i.v.; 20 mg/kg q8h i.v.; and 10 mg/kg q8h++i.v.) of fleroxacin administered intravenously for 4 days. Quantitative bacterial counts, urinary concentrations of fleroxacin and desmethylferoxacin, histopathologic changes, and electron microscopic evaluation of catheter-associated biofilm and mucosal biofilm were performed. The results indicated that the bacterial biofilm on the urinary catheter could be eliminated by fleroxacin at 30 mg/kg q8h i.v. and 20 mg/kg q8h i.v. Fleroxacin concentrations in urine exceeded the levels necessary to destroy E. coli. Viable bacteria were eliminated with the third regimen (10 mg/kg q8h i.v.), but electron microscopy demonstrated remnants of bacterial biofilm. Histopathologic changes were significantly reduced in all fleroxacin-treated rabbits, and scanning electron microscopy showed deterioration of the bacterial biofilm on the surface of the Foley catheter in treated animals. These data suggest that fleroxacin may be useful for treating catheter-related infections because these therapeutic dosages limited ascending infections of the urethra and bladder, eliminated catheter-associated biofilms, and killed planktonic bacteria in urine.
authors.affiliation: Department of Animal Care Services, University of Calgary, Alberta Canada.
authors.forename: D W
authors.initials: DW
authors.lastname: Morck
authors.forename: M E
authors.initials: ME
authors.lastname: Olson
authors.forename: S G
authors.initials: SG
authors.lastname: McKay
authors.forename: K
authors.initials: K
authors.lastname: Lam
authors.forename: B
authors.initials: B
authors.lastname: Prosser
authors.forename: R
authors.initials: R
authors.lastname: Cleeland
authors.forename: J W
authors.initials: JW
authors.lastname: Costerton
mesh_terms: D000818:Animals; D002408:Catheters, Indwelling / Q000009:adverse effects; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000188:drug therapy; D016576:Fleroxacin / Q000627:therapeutic use*; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D014546:Urinary Catheterization / Q000009:adverse effects*; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000652:urine
chemical_list: D016576:Fleroxacin