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Development of resistance to fleroxacin during therapy of experimental methicillin-susceptible Staphylococcus aureus endocarditis.

Abstract
The efficacy of fleroxacin was compared with that of vancomycin by using the rabbit model of methicillin-susceptible Staphylococcus aureus endocarditis. Animals received intravenous therapy with fleroxacin, 30 mg/kg every 8 h, or vancomycin, 17.5 mg/kg every 6 h, for 4 days. Both antimicrobial agents effectively cleared bacteremia and significantly reduced bacterial counts in vegetations and tissues compared with those in untreated controls. However, resistance to fleroxacin at 5- and 10-fold the MIC arose in the test strain of S. aureus in 73 and 27%, respectively, of animals that received the drug. Resistant isolates were found mainly in vegetations and were composed of up to 7% of the residual population recovered from that site. We conclude that fleroxacin is as effective as vancomycin in this model of a serious systemic S. aureus infection, but resistance to the drug may develop during therapy. If similar results are found with other strains of S. aureus during therapy with this or other fluoroquinolones, such data, when they are combined with the high incidence of fluoroquinolone resistance among S. aureus isolates being reported from selected institutions, would support the contention that these drugs should not be used as first-line therapeutic agents for S. aureus infections.
AuthorsG W Kaatz, S M Seo, S L Barriere, L M Albrecht, M J Rybak
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 35 Issue 8 Pg. 1547-50 (Aug 1991) ISSN: 0066-4804 [Print] United States
PMID1929325 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Vancomycin
  • Fleroxacin
  • Methicillin
Topics
  • Animals
  • Drug Resistance, Microbial
  • Endocarditis, Bacterial (drug therapy, microbiology)
  • Fleroxacin (therapeutic use)
  • Male
  • Methicillin (pharmacology)
  • Methicillin Resistance
  • Rabbits
  • Staphylococcal Infections (drug therapy)
  • Staphylococcus aureus (drug effects, physiology)
  • Vancomycin (therapeutic use)

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