ACTIVITY OF BAY Y3118 AGAINST QUINOLONE-SUSCEPTIBLE AND QUINOLONE-RESISTANT GRAM-NEGATIVE AND GRAM-POSITIVE BACTERIA

The activity of Bay y3118 against laboratory strains of bacteria, incl uding those with mutations in gvrA, with decreased expression of outer membrane proteins, and/or that are multiply resistant, and 121 select ed clinical isolates, including highly fluoroquinolone-resistant bacte ria from Spain and Argentina, was determined. Bay y3118 was extremely active (MICs, less than or equal to 1 mu g/ml) against all bacteria, i ncluding quinolone-resistant laboratory strains. However, Bay y3118 wa s less active against 46 of 121 quinolone-resistant clinical isolates, such that greater than or equal to 16 mu g of Bay y3118 per mi was re quired to inhibit 3 isolates. The concentration of Bay y3118 required to inhibit DNA synthesis by 50% correlated well with the MIC. Bay y311 8 had accumulation kinetics similar to those of previously studied Buo roquinolones, e.g., ciprofloxacin, and there was a 50% decrease in the steady-state concentration in those members of the family Enterobacte riaceae that lacked porin proteins. Magnesium chloride at 20 mM appare ntly abolished the accumulation of Bay y3118 into Escherichia coil and reduced the level of accumulation into other gram-negative bacteria a nd Staphylococcus aureus. Carbonyl cyanide m-chlorophenylhydrazone at 100 mu M enhanced the accumulation of Bay y3118 into E. coli, but it h ad a minimal effect on accumulation into S. aureus.