WIN 57273, a new fluoroquinolone with enhanced in vitro activity versus gram-positive pathogens

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Abstract
WIN 57273 is a new fluoroquinolone with excellent in vitro activity versus gram-positive pathogens, including methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis and gentamicin-susceptible and -resistant Enterococcus faecalis. We compared the microdilution MICs and MBCs of this compound to those of other antimicrobial agents for more than 30 clinical isolates of each of these groups of organisms and found that with few exceptions, it was at least 10 times more active than all other drugs tested. Selection for resistance to ciprofloxacin (greater than or equal to 5 micrograms/ml) or WIN 57273 (greater than or equal to 0.16 microgram/ml) by the gradient plate method produced mutants with diminished susceptibility to the other fluoroquinolone; however, the MICs and MBCs of WIN 57273 for such strains were still quite low and remained below the preliminary susceptibility breakpoint (less than or equal to 2 micrograms/ml). Spontaneous mutations conferring resistance to two and five times the WIN 57273 MIC were detectable at low frequencies for S. aureus and S. epidermidis; such mutations were virtually undetectable for E. faecalis. Further testing is necessary to establish if the effectiveness of WIN 57273 is maintained in vivo, first in animals and then in humans with infections caused by methicillin-susceptible and -resistant strains of S. aureus and S. epidermidis or gentamicin-susceptible and -resistant strains of E. faecalis.