YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

In vitro and In vivo Activity of DW286, an Experimental Fluoronaphthyridione, against Gram-Positive Bacteria

새로운 Fluoronaphthyridinone계 항균제 DW286의 그람 양성세균에 대한 항균 활성

  • Kwak, Jin-Hwan (School of Life Science, Handong Global University) ;
  • Park, Hee Soo (School of Life Science, Handong Global University) ;
  • Jung, Sung Ji (School of Life Science, Handong Global University) ;
  • Jeong, Ji-Woong (School of Life Science, Handong Global University) ;
  • Kim, Joseph (School of Life Science, Handong Global University) ;
  • Choi, Dong-Rack (Dong Wha Pharmaceutical Industry Ltd.) ;
  • Choi, Eung-Chil (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
  • Received : 2012.08.28
  • Accepted : 2012.09.26
  • Published : 2012.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

In vitro antibacterial activity of DW286 was tested against recently collected clinical isolates of Gram-positive strains by the two fold agar dilution method. In vivo activity of DW286 was also determined against systemic infections in mice caused by Staphylococcus aureus. DW286 showed 16~64-fold more potent in vitro activities than ciprofloxacin against Gram-positive bacteria. Against systemic infection model caused by two S. aureus strains, one being methicillin-susceptible and the other methicillin-resistant, DW286 ($ED_{50}s$, 0.16 mg/kg and 4.36 mg/kg, respectively) was more potent than gemifloxacin (1.37 mg/kg, 26.58 mg/kg, respectively).

Keywords

Acknowledgement

Supported by : 한동대학교

References

  1. Levy, S. B. and Marshall, B. : Antibacterial resistance worldwide: causes, challenges and responses. Nat. Med. 10, s122 (2004).
  2. Livermore, D., M. : The need for new antibiotics. Clin. Microbiol. Infect. 10, 1 (2004).
  3. Wise, R. : BSAC working party on the urgent need: Regenerating antibacterial drug discovery and development. J. Antimicrob. Chemother 66, 1939 (2011).
  4. Jabes, D. : The antibiotic R&D pipeline: an update. Curr. Opin. in Microbiol. 14, 564 (2011).
  5. Hooper, D. C. and Rubinstein, E. : Quinolone antimicrobial agents. ASM Press (2003).
  6. Yun, H. J., Min, Y. H., Lim, J. A., Kang, J. W., Kim, S. Y., Kim, M. J., Jeong, J. H., Choi, Y. J., Kwon, H. J., Jung, Y. H., Shim, M. J. and Choi, E. C. : In vitro and in vivo antibacterial activities of DW286, a new fluoronaphthyridone antibiotic. Antimicrob. Agents Chemother. 46, 3071 (2002).
  7. Yun, H. J., Min, Y. H., Jo, Y. W., Shim, M. J. and Choi, E. C. : Increased antibacterial activity of DW286, a novel fluoronaphtyridone antibiotic, against Staphylococcus aureus strains with defined mutations in DNA gyrase and topoisomerase IV. Int. J. Antimicrob. Agents 25, 334 (2005).
  8. Park, H. S., Jung, S. J., Choi, D. R. and Kwak, J. H. : Antimicrobial activity of DW286 against Streptococcus pneumonia Int. J. Antimicrob. Agents 36, 230 (2010).
  9. Park, H. S., Kim, H. J., Seol, M. J., Choi, D. R., Choi, E. C. and Kwak, J. H. : In vitro and in vivo antibacterial activities of DW-224a, a new fluoronaphthyridone. Antimicrob. Agents Chemother. 50, 2261 (2006).
  10. Clinical and Laboratory Standards Institute (CLSI), Performance standards for antimicrobial susceptibility testing; 18th information Supplement. CLSI Document M100-S18, CLSI, Wayne, PA (2008).
  11. Bliss, C. I. : Statistics in bioassay. Academic Press, Inc., New York (1985).
  12. De Azavedo, J. C., Duncan, C. L., Kilburn, L., Downar, J., Kong, B., Lad, S., Low, D. E. and Bast, D. J. : Relative potential for selection of quinolone-resistance-determining-region mutations in Streptococcus pneumoniae by gemifloxacin, gatifloxacin and moxifloxacin. J. Chemother. 18, 373 (2006).
  13. Fernandez, J., Hilliard, J. J., Morrow, B. J., Melton, J. L., Flamm, R. K., Barron, A. M. and Lynch, A. S. : Efficacy of a new fluoroquinolone, JNJ-Q2, in murine models of Staphylococcus aureus and Streptococcus pneumoniae skin, respiratory, and systemic infections. Antimicrob. Agents Chemother. 55, 5522 (2011).
  14. Emami, S., Shafiee, A. and Foroumadi, A. : Structural features of new quinolones and relationship to antibacterial activity against Gram-positive bacteria. Mini Rev. Med. Chem. 4, 375 (2006).