In vitro activities of the quinolone antimicrobial agents A-56619 and A-56620

The in vitro activities of two new quinolone antimicrobial agents, A-56619 and A-56620, were compared with those of norfloxacin, ciprofloxacin, and other antimicrobial agents. The activity of A-56620 was comparable to that of ciprofloxacin against Escherichia coli, Enterobacter cloacae, and Aeromonas hydrophila (MICs for 90% of the strains were less than or equal to 0.06 micrograms/ml); Acinetobacter anitratus and Staphylococcus aureus (MIC for 90% of the strains was 0.5 micrograms/ml); and most streptococci. Against other gram-negative strains, A-56620 demonstrated activity comparable to that of norfloxacin, but the new drug was two to eight times more active than norfloxacin against gram-positive isolates. A-56620 was more active than A-56619 against most gram-negative organisms tested. Of the members of the family Enterobacteriaceae examined, 88% were inhibited by A-56619 and 99% by A-56620 at concentrations of less than or equal to 1.0 microgram/ml. By time-kill methods, the new quinolones were bactericidal against gram-negative bacilli during the first 6 h of incubation, but against S. aureus and enterococci the drugs were primarily bacteriostatic during this period. The frequency of spontaneous resistance to 10 micrograms of these drugs per ml was less than 10(-8) for all species tested except E. cloacae, but by serial passage through incremental concentrations of the antimicrobial agents, colonies many-fold more resistant than the initial isolate could be selected. However, resistance to concentrations of the drug greater than 100 micrograms/ml remained stable after passage on antibiotic-free media in only 1 of 35 strains tested.