title: In vivo antianaerobe activity of DS-8587, a new fluoroquinolone, against Fusobacterium necrophorum in a mouse model.
abstract: DS-8587 is a novel parenteral fluoroquinolone, which has an activity equivalent to sitafloxacin against various pathogens including anaerobes. We examined the in vivo anti-anaerobic activity of DS-8587, and compared it with that of levofloxacin (LVFX), using a murine model of Fusobacterium necrophorum-induced liver abscess developed via blood borne infection. Mice with liver abscess infection caused by F. necrophorum were treated with saline (control), DS-8587 (0.8, 4, and 20 mg/kg twice daily), or LVFX (20 and 100 mg/kg) for a day. After treatment, the number of viable bacteria in liver was analyzed. We also analyzed the pharmacokinetics of these agents in plasma and the liver after initial treatment. The MICs of DS-8587 and LVFX were 0.015 and 1 mg/mL, respectively. DS-8587 eradicated the viable bacteria in the liver even at doses as low as 4 mg/kg. In contrast, the liver bacteria were not eradicated in any of the LVFX-treated mice even at a dose of 100 mg/kg (P < 0.05 compared with DS-8587, 4 or 20 mg/kg). The pharmacokinetic parameter AUC/MIC ratios for DS-8587 (4 mg/kg) and LVFX (100 mg/kg) were 96.7 and 60.8 in plasma and 600 and 145.6 in the liver, respectively. The AUC/MIC ratio showed the best correlation with efficacy of DS-8587. DS-8587 significantly reduced the number of viable bacteria in a murine model of F. necrophorum-induced liver abscess compared to LVFX. Our study demonstrated that the anti-anaerobic activity of quinolones in vivo was different from the MICs in vitro.
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; First Department of Internal Medicine, Hokkaido University Hospital, Hokkaido, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nagaoka
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. Electronic address: k-yanagi@net.nagasaki-u.ac.jp.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Morinaga
authors.affiliation: Biological Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kurosaka
authors.affiliation: Biological Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hoshino
authors.affiliation: Second Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Global COE Program, Nagasaki University, Nagasaki, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000818:Animals; D001421:Bacteria, Anaerobic / Q000187:drug effects*; D004195:Disease Models, Animal; D024841:Fluoroquinolones / Q000494:pharmacology*; D005675:Fusobacterium necrophorum / Q000187:drug effects*; D064704:Levofloxacin / Q000494:pharmacology; D008099:Liver / Q000382:microbiology; D008100:Liver Abscess / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests / Q000379:methods
chemical_list: C000594795:DS-8587; D024841:Fluoroquinolones; D064704:Levofloxacin; C076246:sitafloxacin
keywords: Anaerobe; Fluoroquinolone; Fusobacterium necrophorum; Sitafloxacin