Open AccessIn Vitro and In Vivo Antibacterial Activities of DC-159a, a New Fluoroquinolone
Author(s) -
Kazuki Hoshino,
Kazuhiro Inoue,
Yoichi Murakami,
Yuichi Kurosaka,
Kei Namba,
Yoshinori Kashimoto,
Saori Uoyama,
Ryo Okumura,
Saito Higuchi,
Tomoyuki Otani
Publication year - 2008
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00853-07
Subject(s) - in vivo , in vitro , antibacterial agent , microbiology and biotechnology , antibacterial activity , pharmacology , chemistry , antibiotics , biology , bacteria , biochemistry , genetics
DC-159a is a new 8-methoxy fluoroquinolone that possesses a broad spectrum of antibacterial activity, with extended activity against gram-positive pathogens, especially streptococci and staphylococci from patients with community-acquired infections. DC-159a showed activity againstStreptococcus spp. (MIC90 , 0.12 μg/ml) and inhibited the growth of 90% of levofloxacin-intermediate and -resistant strains at 1 μg/ml. The MIC90 s of DC-159a againstStaphylococcus spp. were 0.5 μg/ml or less. Against quinolone- and methicillin-resistantStaphylococcus aureus strains, however, the MIC90 of DC-159a was 8 μg/ml. DC-159a was the most active againstEnterococcus spp. (MIC90 , 4 to 8 μg/ml) and was more active than the marketed fluoroquinolones, such as levofloxacin, ciprofloxacin, and moxifloxacin. The MIC90 s of DC-159a againstHaemophilus influenzae, Moraxella catarrhalis , andKlebsiella pneumoniae were 0.015, 0.06, and 0.25 μg/ml, respectively. The activity of DC-159a againstMycoplasma pneumoniae was eightfold more potent than that of levofloxacin. The MICs of DC-159a againstChlamydophila pneumoniae were comparable to those of moxifloxacin, and DC-159a was more potent than levofloxacin. The MIC90 s of DC-159a againstPeptostreptococcus spp.,Clostridium difficile , andBacteroides fragilis were 0.5, 4, and 2 μg/ml, respectively; and among the quinolones tested it showed the highest level of activity against anaerobic organisms. DC-159a demonstrated rapid bactericidal activity against quinolone-resistantStreptococcus pneumoniae strains both in vitro and in vivo. In vitro, DC-159a showed faster killing than moxifloxacin and garenoxacin. The bactericidal activity of DC-159a in a murine muscle infection model was revealed to be superior to that of moxifloxacin. These activities carried over to the in vivo efficacy in the murine pneumonia model, in which treatment with DC-159a led to bactericidal activity superior to those of the other agents tested.