title: Synergistic effect of fosfomycin and fluoroquinolones against Pseudomonas aeruginosa growing in a biofilm.
abstract: Ulifloxacin is the active form of the prodrug prulifloxacin and shows a highly potent antipseudomonal activity. In this study, we examined the combined effect of fosfomycin and ulifloxacin against Pseudomonas aeruginosa (P. aeruginosa) growing in a biofilm using a modified Robbins device with artificial urine, and compared it to that of the combination of fosfomycin and ciprofloxacin or levofloxacin. An ATP bioluminescence assay was used to evaluate the antibacterial activity of the agents against sessile cells in a mature biofilm developed on a silicon disk. The total bioactivity of P. aeruginosa growing in a biofilm that had not been fully eradicated by fosfomycin or any of the fluoroquinolones alone at 10 times the MIC decreased after combination treatment with fosfomycin and fluoroquinolones. Morphological changes occurred in a time-dependent fashion; namely, swollen and/or rounding cells emerged within a couple of hours after combination treatment, marking the initial stage in the process leading to the destruction of the biofilms. We could not find any difference among the 3 fluoroquinolones with regard to their synergistic effects when administered with fosfomycin. The combination treatment of fosfomycin and fluoroquinolones with highly potent antipseudomonal activities was effective in eradicating sessile cells of P. aeruginosa in the biofilm and promises to be beneficial against biofilm-associated infectious diseases.
authors.affiliation: Infectious Disease Research Laboratories, Meiji Seika Kaisha, Ltd., 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: Reiko
authors.initials: R
authors.lastname: Kariyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Monden
authors.forename: Muneo
authors.initials: M
authors.lastname: Hikida
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002939:Ciprofloxacin / Q000494:pharmacology; D004357:Drug Synergism; D024841:Fluoroquinolones / Q000494:pharmacology*; D005578:Fosfomycin / Q000494:pharmacology*; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development* / Q000648:ultrastructure; D015363:Quinolones / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D010879:Piperazines; D015363:Quinolones; D005578:Fosfomycin; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin; C074190:ulifloxacin