Cinoxacin (compound 64716) is a synthetic organic acid with antibacterial activity against most aerobic gram-negative bacilli. Minimal inhibitory concentrations of cinoxacin (agar-dilution method) were determined for 419 strains. Escherichia coli was the most susceptible group of organisms. The majority of Klebsiella sp., Enterobacter sp.. Proteus sp., and Serratia marcescens were inhibited by 8 qg of cinoxacin per ml. Pseudomonas aeruginosa and all gram-positive isolates tested were resistant to 64 ,ug or less of cinoxacin per ml.Zones of inhibition using a 30-,ug disk correlated well with agar-dilution minimal inhibitory concentrations (r = -0.9). Cinoxacin was bactericidal when tested with inocula of 5 x 106 organisms per ml. Resistance to cinoxacin was readily developed in all three strains tested by serial passage on drug-containing agar. The in vitro properties of this agent were similar to those of nalidixic acid.is a synthetic organic acid with a cinnoline (1-2-benzodiazine) as its basic ring. structure. This agent, previously called compound 64716, has been shown to have antibacterial activity against gramnegative bacilli recovered from patients with urinary tract infections (7). The present study evaluated the in vitro susceptibility of different organisms to this agent and to nalidixic acid (NA), as well as the potential for development of bacterial resistance to these drugs. (MICs) of both agents were determined for a small number of isolates by the broth-dilution method. Serial twofold dilutions of drug were made in 0.5-ml volumes of Trypticase soy broth (TSB) (Baltimore Biological Laboratories) yielding final concentrations ranging from 2 to 256 Mg of drug per ml. Each tube was inoculated with 0.5 ml of either a 10-4 dilution, or a 10-2 dilution of a broth culture incubated overnight at 37 C. MICs wore determined after incubation at 37 C for 20 h.
MATERIALS AND METHODS(ii) Agar-dilution method. The MICs of cinoxacin for 419 strains were determined by the agar-dilution method; 131 of these isolates were also tested with NA by the same method (2). The 131 strains selected for testing with NA were representative of the population of 419 organisms, each group having comparable geometric mean MICs of cinoxacin.Square petri dishes (100 by 15 mm) (Falcon) were each filled with 20 ml of Mueller-Hinton agar (BBL) containing, in twofold dilutions, 1 to 256 Mg of drug per ml. Drug-containing plates were stored at 4 C for up to 1 week before use. The bacterial inoculum was prepared by growing individual strains overnight in 2 ml of TSB at 37 C, with subsequent 1:100 dilution in distilled water prior to inoculation onto drug-contain-