WCK 771, the
arginine salt of
S-(-)-nadifloxacin, was evaluated in animal models of
staphylococcal infection and in vitro. For 302
methicillin-susceptible strains the MIC at which 50% of isolates are inhibited (MIC50) and the MIC90 of
WCK 771 were 0.03 and 0.03 microg/ml, respectively, and for 198 methicillin-resistant strains the MIC50 and the MIC90 were 0.5 and 1.0 microg/ml, respectively. All
methicillin-susceptible staphylococci were
quinolone susceptible, and almost all methicillin-resistant staphylococci were
quinolone resistant.
WCK 771 was more potent than
moxifloxacin,
trovafloxacin,
levofloxacin, and
ciprofloxacin and had potency comparable to that of
clinafloxacin. Only
WCK 771 and
clinafloxacin demonstrated strong potencies against vancomycin-intermediate Staphylococcus aureus strains (MICs = 1 microg/ml).
WCK 771 is not a substrate of the NorA pump, as evident from the lack of an effect of
reserpine on the MICs and similar protective doses against
infections caused by efflux-positive and -negative staphylococci.
WCK 771 was effective by both the oral and the subcutaneous routes in mice infected intraperitoneally with
quinolone-susceptible
methicillin-susceptible S. aureus (MSSA) strains. For
infections caused by
quinolone-resistant methicillin-resistant S. aureus (MRSA) strains, the activity of
WCK 771 administered subcutaneously was superior to those of
trovafloxacin and
sparfloxacin, with a 50% effective dose range of 27.8 to 46.8 mg/kg of
body weight. The activity of
WCK 771 was superior to those of
moxifloxacin,
vancomycin, and
linezolid in a mouse
cellulitis model of
infection caused by one MSSA and two MRSA strains, with effective doses of 2.5 and 5 mg/kg for the MSSA strain and 10-fold higher effective doses for MRSA strains.
WCK 771, like
vancomycin and
linezolid, eradicated MRSA from mouse liver, spleen, kidney, and lung when it was administered subcutaneously at a dose of 50 mg/kg for four doses. These studies have demonstrated the effectiveness of
WCK 771, administered orally and parenterally, for the treatment of diverse
staphylococcal infections in mice, including those caused by
quinolone-resistant strains.