title: Treatment of Pseudomonas aeruginosa biofilms with a combination of fluoroquinolones and fosfomycin in a rat urinary tract infection model.
abstract: Foreign body-associated infectious disease is currently one of the most problematic hospital-acquired infections. Patients with placement of urinary catheters are especially susceptible to such infection, that is biofilm infection. In this study, we focused on the therapeutic efficacy of prulifloxacin (PUFX) against Pseudomonas aeruginosa OP 14-210, isolated from a patient with complicated urinary tract infection. This microbe formed a biofilm on the surface of a polyethylene tube (PT) placed in a rat bladder without surgical manipulation. In addition, we attempted to eradicate the biofilm by treatment with a combination of PUFX and fosfomycin (FOM). A single oral administration of PUFX at a dose of 20 mg/kg was effective against P. aeruginosa as a biofilm, yielding a significant reduction in CFU per PT of approximately 1 log(10) CFU/PT compared with that in untreated controls. A similar therapeutic effect was also observed in levofloxacin-treated rats, and albeit slightly weaker, in ciprofloxacin-treated animals as well. Because 3 days' consecutive treatment with each fluoroquinolone did not further decrease the viable cell counts on the PT, we tested the efficacy of combining PUFX and FOM. These two drugs, administered once a day for 3 days, at doses of 20 and 100 mg/kg, respectively, resulted in significant decreases of viable cell counts on the PT of more than 1.5 log(10) CFU/PT compared with PUFX alone (P < 0.05). As seen by scanning electron microscopy, destruction and disappearance of multilayer biofilms occurred after treatment with this drug combination. Such combination therapy with PUFX and FOM may be advantageous for treating biofilm-related infectious diseases.
authors.affiliation: Pharmacology Research Labs., Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Morooka-Cho 760, Kohoku-ku, Yokohama 222-8567, Japan. takeshi_mikuniya@meiji.co.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mikuniya
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kato
authors.forename: Takashi
authors.initials: T
authors.lastname: Ida
authors.forename: Kazunori
authors.initials: K
authors.lastname: Maebashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Monden
authors.forename: Reiko
authors.initials: R
authors.lastname: Kariyama
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000254:growth & development*; D002408:Catheters, Indwelling / Q000009:adverse effects / Q000382:microbiology; D004148:Dioxolanes / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology*; D005578:Fosfomycin / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D010879:Piperazines / Q000494:pharmacology*; D020959:Polyethylene; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D014546:Urinary Catheterization / Q000009:adverse effects; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D004148:Dioxolanes; D024841:Fluoroquinolones; D010879:Piperazines; D015363:Quinolones; D005578:Fosfomycin; D020959:Polyethylene; C074191:prulifloxacin