This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bogdanovich, T.
Right arrow Articles by Appelbaum, P. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bogdanovich, T.
Right arrow Articles by Appelbaum, P. C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2005, p. 3325-3333, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3325-3333.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Antistaphylococcal Activity of DX-619, a New Des-F(6)-Quinolone, Compared to Those of Other Agents

Tatiana Bogdanovich, Duygu Esel, Linda M. Kelly, Bülent Bozdogan, Kim Credito, Gengrong Lin, Kathy Smith, Lois M. Ednie, Dianne B. Hoellman, and Peter C. Appelbaum*

Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033

Received 2 March 2005/ Returned for modification 3 April 2005/ Accepted 10 April 2005

The in vitro activity of DX-619, a new des-F(6)-quinolone, was tested against staphylococci and compared to those of other antimicrobials. DX-619 had the lowest MIC ranges/MIC50s/MIC90s (µg/ml) against 131 Staphylococcus aureus strains (≤0.002 to 2.0/0.06/0.5) and 128 coagulase-negative staphylococci (0.004 to 0.25/0.016/0.125). Among strains tested, 76 S. aureus strains and 51 coagulase-negative staphylococci were resistant to ciprofloxacin. DX-619 had the lowest MIC50/MIC90 values against 127 quinolone-resistant staphylococci (0.125/0.5), followed by sitafloxacin (0.5/4), moxifloxacin (2/8), gatifloxacin (4/16), levofloxacin (16/>32), and ciprofloxacin (>32/>32). Raised quinolone MICs were associated with mutations in GyrA (S84L) and single or double mutations in GrlA (S80F or Y; E84K, G, or V) in all S. aureus strains tested. A recent vancomycin-resistant S. aureus (VRSA) strain (Hershey) was resistant to available quinolones and was inhibited by DX-619 at 0.25 µg/ml and sitafloxacin at 1.0 µg/ml. Vancomycin (except VRSA), linezolid, ranbezolid, tigecycline, and quinupristin-dalfopristin were active against all strains, and teicoplanin was active against S. aureus but less active against coagulase-negative staphylococci. DX-619 produced resistant mutants with MICs of 1 to >32 µg/ml after <50 days of selection compared to 16 to >32 µg/ml for ciprofloxacin, sitafloxacin, moxifloxacin, and gatifloxacin. DX-619 and sitafloxacin were also more active than other tested drugs against selected mutants and had the lowest mutation frequencies in single-step resistance selection. DX-619 and sitafloxacin were bactericidal against six quinolone-resistant (including the VRSA) and seven quinolone-susceptible strains tested, whereas gatifloxacin, moxifloxacin, levofloxacin, and ciprofloxacin were bactericidal against 11, 10, 7, and 5 strains at 4x MIC after 24 h, respectively. DX-619 was also bactericidal against one other VRSA strain, five vancomycin-intermediate S. aureus strains, and four vancomycin-intermediate coagulase-negative staphylococci. Linezolid, ranbezolid, and tigecycline were bacteriostatic and quinupristin-dalfopristin, teicoplanin, and vancomycin were bactericidal against two, eight, and nine strains, and daptomycin and oritavancin were rapidly bactericidal against all strains, including the VRSA. DX-619 has potent in vitro activity against staphylococci, including methicillin-, ciprofloxacin-, and vancomycin-resistant strains.

* Corresponding author. Mailing address: Department of Pathology, Hershey Medical Center, P.O. Box 850, Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail: pappelbaum{at}psu.edu.

Antimicrobial Agents and Chemotherapy, August 2005, p. 3325-3333, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3325-3333.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kosowska-Shick, K., Clark, C., Pankuch, G. A., McGhee, P., Dewasse, B., Beachel, L., Appelbaum, P. C. (2009). Activity of Telavancin against Staphylococci and Enterococci Determined by MIC and Resistance Selection Studies. Antimicrob. Agents Chemother. 53: 4217-4224 [Abstract] [Full Text]  
  • Clark, C., Kosowska-Shick, K., McGhee, P., Dewasse, B., Beachel, L., Appelbaum, P. C. (2009). Resistance Selection Studies Comparing the Activity of Razupenem (PTZ601) to Vancomycin and Linezolid against Eight Methicillin-Resistant and Two Methicillin-Susceptible Staphylococcus aureus Strains. Antimicrob. Agents Chemother. 53: 3118-3121 [Abstract] [Full Text]  
  • Watanabe, S., Ito, T., Hiramatsu, K. (2007). Susceptibilities of healthcare- and community-associated methicillin-resistant staphylococci to the novel des-F(6)-quinolone DX-619. J Antimicrob Chemother 60: 1384-1387 [Abstract] [Full Text]  
  • Bogdanovich, T., Clark, C., Kosowska-Shick, K., Dewasse, B., McGhee, P., Appelbaum, P. C. (2007). Antistaphylococcal Activity of CG400549, a New Experimental FabI Inhibitor, Compared with That of Other Agents. Antimicrob. Agents Chemother. 51: 4191-4195 [Abstract] [Full Text]  
  • Sarapa, N., Wickremasingha, P., Ge, N., Weitzman, R., Fuellhart, M., Yen, C., Lloyd-Parks, J. (2007). Lack of Effect of DX-619, a Novel Des-Fluoro(6)-Quinolone, on Glomerular Filtration Rate Measured by Serum Clearance of Cold Iohexol. Antimicrob. Agents Chemother. 51: 1912-1917 [Abstract] [Full Text]  
  • Credito, K., Lin, G., Appelbaum, P. C. (2007). Antistaphylococcal Activity of DX-619 Alone and in Combination with Vancomycin, Teicoplanin, and Linezolid Assessed by Time-Kill Synergy Testing. Antimicrob. Agents Chemother. 51: 1508-1511 [Abstract] [Full Text]  
  • Kosowska-Shick, K., Smith, K., Bogdanovich, T., Ednie, L. M., Jones, R. N., Appelbaum, P. C. (2006). Activity of DX-619 Compared to Other Agents against Viridans Group Streptococci, Streptococcus bovis, and Cardiobacterium hominis. Antimicrob. Agents Chemother. 50: 4191-4194 [Abstract] [Full Text]  
  • Falagas, M. E., Matthaiou, D. K., Vardakas, K. Z. (2006). Fluoroquinolones vs {beta}-Lactams for Empirical Treatment of Immunocompetent Patients With Skin and Soft Tissue Infections: A Meta-analysis of Randomized Controlled Trials. Mayo Clin Proc. 81: 1553-1566 [Abstract] [Full Text]  
  • Tanaka, K., Mikamo, H., Nakao, K., Watanabe, K. (2006). In Vitro Antianaerobic Activity of DX-619, a New Des-Fluoro(6) Quinolone. Antimicrob. Agents Chemother. 50: 3908-3913 [Abstract] [Full Text]  
  • Garcia, I., Ballesta, S., Murillo, C., Perea, E. J., Pascual, A. (2006). Intracellular Penetration and Activity of DX-619 in Human Polymorphonuclear Leukocytes.. Antimicrob. Agents Chemother. 50: 3173-3174 [Abstract] [Full Text]  
  • Wickman, P. A., Black, J. A., Moland, E. S., Thomson, K. S. (2006). In Vitro Activities of DX-619 and Comparison Quinolones against Gram-Positive Cocci.. Antimicrob. Agents Chemother. 50: 2255-2257 [Abstract] [Full Text]  
  • Molitoris, D., Vaisanen, M.-L., Bolanos, M., Finegold, S. M. (2006). In Vitro Activities of DX-619 and Four Comparator Agents against 376 Anaerobic Bacterial Isolates.. Antimicrob. Agents Chemother. 50: 1887-1889 [Abstract] [Full Text]  
  • Strahilevitz, J., Truong-Bolduc, Q. C., Hooper, D. C. (2005). DX-619, a Novel Des-Fluoro(6) Quinolone Manifesting Low Frequency of Selection of Resistant Staphylococcus aureus Mutants: Quinolone Resistance beyond Modification of Type II Topoisomerases. Antimicrob. Agents Chemother. 49: 5051-5057 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»