InVitro Activities ofa Dual-Action Antibacterial Agent, Ro23-9424, andComparative Agents

Theinvitro activity ofthedual-action antibacterial agentRo 23-9424 was comparedwiththoseof cefotaxime, ceftazidime, ciprofloxacin, fleroxacin, imipenem, andamikacin against 358aerobes andanaerobes. TheMIC ranges,MICsfor50and90%ofthestrains (MIC50s andMIC90s), andpercentage ofstrains susceptible foreachagentattherecommended susceptible MICbreakpoint were determined foreachgenus. TheMIC90s (micrograms permilliliter) oftheagents against membersofthefamily Enterobacteriaceae were asfollows: ciprofloxacin, 0.063; Ro23-9424, fleroxacin, andimipenem, 0.5; ceftazidime, 2;amikacin, 4;and cefotaxime, 16.TheMIC90s (micrograms permilliliter) against Pseudomonas andAcinetobacter spp.were as follows: ciprofloxacin, 2;ceftazidime andimipenem,8;Ro23-9424, 16;fleroxacin, 32;amikacin, 64;and cefotaxime, 128.Against gram-positive bacteria, excluding theenterococci, theMIC90s (micrograms per milliliter) were asfollows: ciprofloxacin, 1;imipenem, 4;Ro23-9424 andfleroxacin, 8;amikacin, 64;and ceftazidime andcefotaxime, >128.Against gram-positive bacteria, including theenterococci, theMIC90s changed only forthefollowing agents: Ro23-9424, 16gug/ml; andamikacin, 128gug/ml. Strains ofBranhamella catarrhalis, Haemophilus influenzae, andNeisseria gonorrhoeae were 100%susceptible toRo 23-9424, cefotaxime, ciprofloxacin, andfleroxacin, while theotherthree agents showedsomewhat less activity only against N.gonorrhoeae. Against anaerobes, imipenem was themosteffective agent, while theactivities ofthe other sixagents werevariable. Ro23-9424 isanewdual-action agent inwhichacephalosporin moiety withthesame7-acylamino substituent as ceftriaxone andcefotaxime islinked byanester bondtothe quinolone fleroxacin atthe3'-methyl position. Thisdual