In vitro and in vivo antibacterial activities of DC-159a, a new fluoroquinolone

被引:52
|
作者
Hoshino, Kazuki [1 ]
Inoue, Kazue [1 ]
Murakami, Yoichi [1 ]
Kurosaka, Yuichi [1 ]
Namba, Kenji [1 ]
Kashimoto, Yoshinori [1 ]
Uoyama, Saori [1 ]
Okumura, Ryo [1 ]
Higuchi, Saito [1 ]
Otani, Tsuyoshi [1 ]
机构
[1] Daiichi Sankyo Co Ltd, Biol Res Labs 4, Tokyo 1348630, Japan
关键词
D O I
10.1128/AAC.00853-07
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 against Streptococcus spp. (MIC90, 0.12 mu g/ml) and inhibited the growth of 90% of levofloxacin-intermediate and -resistant strains at 1 mu g/ml. The MIC(90)s of DC-159a against Staphylococcus spp. were 0.5 mu g/ml or less. Against quinolone- and methicillin-resistant Staphylococcus aureus strains, however, the MIC90 of DC-159a was 8 mu g/ml. DC-159a was the most active against Enterococcus spp. (MIC90, 4 to 8 mu g/ml) and was more active than the marketed fluoroquinolones, such as levofloxacin, ciprofloxacin, and moxifloxacin. The MIC(90)s of DC-159a against Haemophilus influenzae, Moraxella catarrhalis, and Klebsiella pneumoniae were 0.015, 0.06, and 0.25 mu g/ml, respectively. The activity of DC-159a against Mycoplasma pneumoniae was eightfold more potent than that of levofloxacin. The MICs of DC-159a against Chlamydophila pneumouiae were comparable to those of moxifloxacin, and DC-159a was more potent than levofloxacin. The MIC(90)s of DC-159a against Peptostreptococcus spp., Clostridium difficile, and Bacteroides fragilis were 0.5, 4, and 2 mu g/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-resistant Streptococcus 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.
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页码:65 / 76
页数:12
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