title: [Bactericidal effect of levofloxacin injection in combination with meropenem against Pseudomonas aeruginosa using an in vitro simulation model with a hollow fiber system].
abstract: An in vitro human plasma concentration simulation model with a hollow fiber system was established and used to evaluate the bactericidal effect of levofloxacin (LVFX) 500mg q.d. in combination with meropenem (MEPM) 1000mg t.i.d. against Pseudomonas aeruginosa. Six clinical isolates of P. aeruginosa which had MEPM MICs of 2 - 16 microg/mL, LVFX MICs of 2 microg/mL, and fractional inhibitory concentration (FIC) indices by the in vitro checkerboard method of 0.625-1 were used. In the treatment with MEPM alone, initial viable counts (10(6)-10(7) CFU/ mL) decreased, but did not reach below the detection limit (100 CFU/mL) and the regrowth of bacteria was observed. In the treatment with LVFX alone, viable counts decreased once below the detection limit, although increased after treatment for 24 hours. On the other hand, in the treatment with LVFX-MEPM combination, more potent bactericidal effects were observed compared to LVFX or MEPM alone in all strains. Especially, in the strains with MEPM MICs of 2 and 4 microg/mL, viable counts rapidly decreased below the detection limit and no regrowth was observed until 24 hours. These results suggested that LVFX-MEPM has a potential to be an effective combination against P. aeruginosa by synergistic rapid bactericidal action in clinical settings, even in the strain against which no significant synergy is confirmed by the traditional in vitro checkerboard method.
authors.affiliation: Biological Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd.
authors.forename: Saori
authors.initials: S
authors.lastname: Uoyama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kanda
authors.forename: Kumi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hoshino
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D006801:Humans; D064704:Levofloxacin; D000077731:Meropenem; D008826:Microbial Sensitivity Tests / Q000379:methods*; D015242:Ofloxacin / Q000008:administration & dosage*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013845:Thienamycins / Q000008:administration & dosage*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D064704:Levofloxacin; D015242:Ofloxacin; D000077731:Meropenem