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Clinical Drug Investigation

, Volume 14, Issue 4, pp 330–336 | Cite as

Comparative In Vitro Activity and Killing Effect of Trovafloxacin, DU-6859a, Levofloxacin and Sparfloxacin against Staphylococcus aureus

Focus on Methicillin-Resistant Isolates
  • E. J. Giamarellos-Bourboulis
  • P. Grecka
  • I. Galani
  • H. Giamarellou
Pharmacodynamics

Summary

The predominance of quinolone resistance among methicillin-resistant Staphylococcus aureus (MRSA) isolates in the nosocomial environment led to the in vitro comparison of trovafloxacin (CP-99,219) and DU-6859a (which are novel fluoroquinolone compounds) with levofloxacin (the L-geometric isomer of ofloxacin) and Sparfloxacin against 152 S. aureus isolates, 104 of which were MRSA. At 2 mg/L trovafloxacin and DU-6859a inhibited 92.3 and 77.9% of MRSA isolates, respectively, possessing lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values than levofloxacin and Sparfloxacin, which inhibited 38.5 and 36.5% of isolates, respectively. In contrast, in the methicillin-susceptible population all tested fluoroquinolones had an equal intrinsic activity. Trovafloxacin possessed a superior killing effect compared with DU-6859a and Sparfloxacin, whereas levofloxacin was the least bactericidal quinolone. Indeed, the effect of trovafloxacin was mainly expressed at a quinolone concentration of 2 × MIC and after 24 hours of growth. However, in levofloxacin- and sparfloxacin-resistant MRSA isolates, DU-6859a had a superior killing effect compared with trovafloxacin. Trovafloxacin had a killing effect in only 20% of DU-6859a-, levofloxacin- and sparfloxacin-resistant isolates. Our findings support trovafloxacin and DU-6859a as highly active in vitro antistaphylococcal agents, especially in MRSA, which merit further clinical investigation.

Keywords

Minimum Inhibitory Concentra Adis International Limited Levofloxacin Antimicrob Agent Drug Invest 
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References

  1. 1.
    Goldstein FW, Acar JF. Epidemiology of quinolone resistance: Europe and North and South America. Drugs 1995; 49 Suppl. 2: 36–42PubMedCrossRefGoogle Scholar
  2. 2.
    Giamarellou H. Activity of quinolones against Gram-positive cocci: clinical features. Drugs 1995; 49 Suppl. 2: 58–66PubMedCrossRefGoogle Scholar
  3. 3.
    Eliopoulos GM. In vitro activity of fluoroquinolones against Gram-positive bacteria. Drugs 1995; 49 Suppl. 2: 48–57PubMedCrossRefGoogle Scholar
  4. 4.
    Coque TM, Singh KY, Murray BE. Comparative in vitro activity of the new fluoroquinolone trovafloxacin (CP-99,219) against Gram-positive cocci. J Antimicrob Chemother 1996; 37(5): 1011–6PubMedCrossRefGoogle Scholar
  5. 5.
    Korten V, Tomayako JF, Murray BE. Comparative in vitro activity of DU-6859a, a new fluoroquinolone agent, against Gram-positive cocci. Antimicrob Agents Chemother 1994; 38(3): 611–5PubMedCrossRefGoogle Scholar
  6. 6.
    Nakane T, Iyobe S, Sato K, et al. In vitro antibacterial activity of DU-6859a, a new fluoroquinolone. Antimicrob Agents Chemother 1995; 39(12): 2822–6PubMedCrossRefGoogle Scholar
  7. 7.
    Patel JA, Pachucki CT, Lentino JR. Synergy of levofloxacin (L-ofloxacin) and oxacillin against quinolone-resistant Staphylococcus aureus measured by the time-kill method. Antimicrob Agents Chemother 1993; 37(2): 339–41PubMedCrossRefGoogle Scholar
  8. 8.
    Baquero F, Canton R. In vitro activity of Sparfloxacin in comparison with currently available antimicrobials against respiratory tract pathogens. J Antimicrob Chemother 1996; 37 Suppl. A: 1–18PubMedCrossRefGoogle Scholar
  9. 9.
    Hindier J. Tests to detect oxacillin (methicillin)-resistant staphylococci with an oxacillin screen plate. In: Isenberg HD, editor. Clinical microbiology procedures handbook. Washington DC: American Society for Microbiology 1992; 5.5. 1–7Google Scholar
  10. 10.
    Archer GL, Pennell E. Detection of methicillin resistance in staphylococci by using a DNA probe. Antimicrob Agents Chemother 1990; 34(9): 1720–4PubMedCrossRefGoogle Scholar
  11. 11.
    Woods GL, Washington JA. Antibacterial susceptibility tests: dilution and disk diffusion methods. In: Murray PR, Baron EJ, Pfaller MA, et al, editors. Manual of clinical microbiology. 6th ed. Washington DC: American Society for Microbiology, 1995; 1327–41Google Scholar
  12. 12.
    Teng R, Harris SC, Nix DE, et al. Pharmacokinetics and safety of trovafloxacin (CP-99,219), a new quinolone antibiotic, following administration of single oral doses to healthy male volunteers. J Antimicrob Chemother 1995; 36(2): 385–94PubMedCrossRefGoogle Scholar
  13. 13.
    Nakashima M, Vematsu J, Kosuge K, et al. Pharmacokinetics and tolerance of DU-6859a, a new fluoroquinolone, after single and multiple oral doses in healthy volunteers. Antimicrob Agents Chemother 1995; 39(1): 170–4PubMedCrossRefGoogle Scholar
  14. 14.
    Child J, Mortiboy D, Andrews JM, et al. Open-label crossover study to determine pharmacokinetics and penetration of two dose regimens of levofloxacin into inflammatory fluid. Antimicrob Agents Chemother 1995; 39(12): 2749–51PubMedCrossRefGoogle Scholar
  15. 15.
    Montay G. Pharmacokinetics of Sparfloxacin in healthy volunteers: a review. J Antimicrob Chemother 1996; 37 Suppl. A: 27–39PubMedCrossRefGoogle Scholar
  16. 16.
    Hindier J. Tests to assess bactericidal activity. In: Isenberg HD, editor. Clinical microbiology procedures handbook. Washington DC: American Society for Microbiology, 1992: 5.16.14–21Google Scholar
  17. 17.
    Gooding BB, Jones RN. In vitro antimicrobial activity of CP-99,219, a novel azabicyclo-naphthyridone. Antimicrob Agents Chemother 1993; 37(2): 349–53PubMedCrossRefGoogle Scholar
  18. 18.
    Child J, Andrews J, Boswell F, et al. The in vitro activity of CP 99,219, a new naphthyridone antimicrobial agent: a comparison with fluoroquinolone agents. J Antimicrob Chemother 1995; 35(6): 869–76PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang YY, Wang F, Zhang J, et al. In vitro antibacterial activity of levofloxacin. Drugs 1995; 49 Suppl. 2: 274–5PubMedCrossRefGoogle Scholar
  20. 20.
    Paradelis AG, Delidou K, Grigoriadou A, et al. The antimicrobial activity of Sparfloxacin, a new quinolone. Drugs 1995; 49 Suppl. 2: 238–9PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  • E. J. Giamarellos-Bourboulis
    • 1
  • P. Grecka
    • 1
  • I. Galani
    • 1
  • H. Giamarellou
    • 1
  1. 1.1st Department of Propedeutic MedicineAthens Medical SchoolAthensGreece

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