• Medientyp: E-Artikel
  • Titel: Antistaphylococcal Activity of DX-619, a New Des-F(6)-Quinolone, Compared to Those of Other Agents
  • Beteiligte: Bogdanovich, Tatiana; Esel, Duygu; Kelly, Linda M.; Bozdogan, Bülent; Credito, Kim; Lin, Gengrong; Smith, Kathy; Ednie, Lois M.; Hoellman, Dianne B.; Appelbaum, Peter C.
  • Erschienen: American Society for Microbiology, 2005
  • Erschienen in: Antimicrobial Agents and Chemotherapy
  • Sprache: Englisch
  • DOI: 10.1128/aac.49.8.3325-3333.2005
  • ISSN: 0066-4804; 1098-6596
  • Schlagwörter: Infectious Diseases ; Pharmacology (medical) ; Pharmacology
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  • Beschreibung: <jats:title>ABSTRACT</jats:title> <jats:p> 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/MIC <jats:sub>50</jats:sub> s/MIC <jats:sub>90</jats:sub> s (μg/ml) against 131 <jats:italic>Staphylococcus aureus</jats:italic> 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 <jats:italic>S. aureus</jats:italic> strains and 51 coagulase-negative staphylococci were resistant to ciprofloxacin. DX-619 had the lowest MIC <jats:sub>50</jats:sub> /MIC <jats:sub>90</jats:sub> values against 127 quinolone-resistant staphylococci (0.125/0.5), followed by sitafloxacin (0.5/4), moxifloxacin (2/8), gatifloxacin (4/16), levofloxacin (16/&gt;32), and ciprofloxacin (&gt;32/&gt;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 <jats:italic>S. aureus</jats:italic> strains tested. A recent vancomycin-resistant <jats:italic>S. aureus</jats:italic> (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 <jats:italic>S. aureus</jats:italic> but less active against coagulase-negative staphylococci. DX-619 produced resistant mutants with MICs of 1 to &gt;32μ g/ml after &lt;50 days of selection compared to 16 to&gt; 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 4× MIC after 24 h, respectively. DX-619 was also bactericidal against one other VRSA strain, five vancomycin-intermediate <jats:italic>S. aureus</jats:italic> 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. </jats:p>
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