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Antimicrobial Agents and Chemotherapy, January 2008, p. 65-76, Vol. 52, No. 1
0066-4804/08/$08.00+0     doi:10.1128/AAC.00853-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

In Vitro and In Vivo Antibacterial Activities of DC-159a, a New Fluoroquinolone{triangledown}

Kazuki Hoshino,* Kazue Inoue, Yoichi Murakami, Yuichi Kurosaka, Kenji Namba, Yoshinori Kashimoto, Saori Uoyama, Ryo Okumura, Saito Higuchi, and Tsuyoshi Otani

Biological Research Laboratories IV, Daiichi Sankyo Co., Ltd., 16-13, 1-Chome Kitakasai, Edogawa-ku, Tokyo 134-8630

Received 29 June 2007/ Returned for modification 27 July 2007/ Accepted 21 September 2007

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 µg/ml) and inhibited the growth of 90% of levofloxacin-intermediate and -resistant strains at 1 µg/ml. The MIC90s of DC-159a against Staphylococcus spp. were 0.5 µg/ml or less. Against quinolone- and methicillin-resistant Staphylococcus aureus strains, however, the MIC90 of DC-159a was 8 µg/ml. DC-159a was the most active against Enterococcus spp. (MIC90, 4 to 8 µg/ml) and was more active than the marketed fluoroquinolones, such as levofloxacin, ciprofloxacin, and moxifloxacin. The MIC90s of DC-159a against Haemophilus influenzae, Moraxella catarrhalis, and Klebsiella pneumoniae were 0.015, 0.06, and 0.25 µg/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 pneumoniae were comparable to those of moxifloxacin, and DC-159a was more potent than levofloxacin. The MIC90s of DC-159a against Peptostreptococcus spp., Clostridium difficile, and Bacteroides 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-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.

* Corresponding author. Mailing address: Biological Research Laboratories IV, Daiichi Sankyo Co., Ltd., 16-13, 1-Chome Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan. Phone: 81-3-5696-8245. Fax: 81-3-5696-4264. E-mail: hoshino.kazuki.d6{at}daiichisankyo.co.jp

{triangledown} Published ahead of print on 15 October 2007.

Antimicrobial Agents and Chemotherapy, January 2008, p. 65-76, Vol. 52, No. 1
0066-4804/08/$08.00+0     doi:10.1128/AAC.00853-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jones, R. N., Fritsche, T. R., Sader, H. S. (2008). Antimicrobial Activity of DC-159a, a New Fluoroquinolone, against 1,149 Recently Collected Clinical Isolates. Antimicrob. Agents Chemother. 52: 3763-3775 [Abstract] [Full Text]  
  • Waites, K. B., Crabb, D. M., Duffy, L. B. (2008). Comparative In Vitro Activities of the Investigational Fluoroquinolone DC-159a and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas. Antimicrob. Agents Chemother. 52: 3776-3778 [Abstract] [Full Text]  
  • Okumura, R., Hirata, T., Onodera, Y., Hoshino, K., Otani, T., Yamamoto, T. (2008). Dual-targeting properties of the 3-aminopyrrolidyl quinolones, DC-159a and sitafloxacin, against DNA gyrase and topoisomerase IV: contribution to reducing in vitro emergence of quinolone-resistant Streptococcus pneumoniae. J Antimicrob Chemother 62: 98-104 [Abstract] [Full Text]  
  • Clark, C., Smith, K., Ednie, L., Bogdanovich, T., Dewasse, B., McGhee, P., Appelbaum, P. C. (2008). In Vitro Activity of DC-159a, a New Broad-Spectrum Fluoroquinolone, Compared with That of Other Agents against Drug-Susceptible and -Resistant Pneumococci. Antimicrob. Agents Chemother. 52: 77-84 [Abstract] [Full Text]  


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