The antimicrobial activity of cinoxacin, 1-ethyl-4(1H)-oxo- [1,3]dioxolo [4,5-g]cinnoline-3-carboxylic acid, previously reported as compound 64716, was determined and compared with other antimicrobial agents at a dosage of 12 mg/kg once daily in a descending pyelonephritis rat model with Escherichia coli and Proteus mirabilis as infecting organisms. Cinoxacin was considerably more effective than either nalidixic acid or oxolinic acid when all three were administered orally at 3 mg/kg four times daily. (BBL), suspended in brain heart infusion broth (BBL), divided into 0.2-ml portions, and frozen in liquid nitrogen. Bacterial suspensions for rat inoculations were prepared daily by seeding a 50-ml flask of brain heart infusion broth from a frozen ampoule and growing the culture ovemight at 37 C on a shaker. The E. coli culture was diluted to 5 x 108 colony-forming units per ml, and the P. mirabilis culture was diluted to 1 x 101 colony-forming units per ml.Antimicrobial agents. Cinoxacin, cephaloridine, cefazolin, tobramycin, and cephaloglycin were prepared in the Lilly Research Laboratories. Other agents employed and their sources were: carbenicillin indanyl sodium, Pfizer, Inc.; disodium carbenicillin, J. B. Roerig, Division of Pfizer, Inc.; gentamicin sulfate, Schering Corp.; sodium ampicillin, Bristol Laboratories, Division of Bristol-Myers Co.; nitrofurantoin, Eaton Laboratories, Division of MortonNorwich Products, Inc.; nalidixic acid, Winthrop Laboratories, Division of Sterling Drug, Inc.; oxolinic acid, Warner-Lambert Research Institute; and trimethoprim-sulfamethoxazole (1:5), Roche Laboratories, Division of Hoffman-LaRoche, Inc. Certain of the antimicrobial compounds were administered by gavage once, twice, or four times daily for 7 days, and others were injected subcutaneously. All compounds were suspended in 0.125% carboxymethylcellulose.Experimental rat infections. Female, randombred albino rats (Cox-Wistar) weighing 190 to 210 g were anesthetized by intraperitoneal injection of 12 mg of sodium methohexital supplemented as necessary. The experimental pyelonephritis model was based on the studies of Guze and Beeson in which the left ureter was occluded for 20 min, followed by injection of 0.5 ml of the test organism in the femoral vein (4). Antimicrobial therapy commenced 4 to 5 h postinfection except where otherwise noted. Four hours after the last treatment the rats were sacrificed, and the left kidney was removed and homogenized in a Duall grinder containing 9 ml of physiological saline. This represented a 10-1 dilution of the kidney tissue. Additional 10-fold dilutions in saline were based on the anticipated bacterial cells present in the tissue homogenate. Finally, duplicate agar pour plates were made from several of these dilutions, and
