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.