The in vitro spectrum of a novel des-fluoro (6) quinolone, garenoxacin (BMS-284756), was compared with that of ciprofloxacin, levofloxacin, and trovafloxacin against 736 clinical isolates from cancer patients. Garenoxacin was the most active agent overall against Gram-positive organisms, with potent activity against Aerococcus spp., Micrococcus spp., Rhodococcus equi, Stomatococcus mucilaginous, Bacillus spp., Enterococcus faecalis, Listeria monocytogenes, methicillin-susceptible Staphylococcus spp., and all beta-hemolytic and viridans streptococci. Although ciprofloxacin was the most active agent tested against the Enterobacteriaceae garenoxacin inhibited the majority of these isolates at <or=4.0 microg/ml, its proposed susceptibility break-point. All 4 agents had sub-optimal activity against Pseudomonas aeruginosa and variable activity against other non-fermenters, with Stenotrophomonas maltophila and Alcaligenes spp. being the most resistant isolates. The overall broad spectrum of garenoxacin warrants its evaluation for the prevention or treatment of infections in cancer patients.