In vitro activity of Ro 23-9424, a dual-action cephalosporin, compared with activities of other antibiotics

Abstract

The in vitro activity of , which is desacetyl-cefotaxime linked to fleroxacin, was compared with the activities of cefotaxime, desacetyl-cefotaxime, fleroxacin, ofloxacin, and ciprofloxacin. It Since 1980 a number of new quinolone carboxylic acid compounds have been synthesized. These include norfloxacin, pefloxacin, enoxacin, ofloxacin, ciprofloxacin, and fleroxacin (3). Although these compounds have a very broad spectrum of antimicrobial activity, some of them are marginally active or inactive against anaerobic bacteria, beta-hemolytic streptococci, Streptococcus pneumoniae, enterococci, and Listeria monocytogenes (A. L. Barry, Antimicrob. Newsl. 5:69-76, 1988). Fluoroquinolones and cephalosporins have the potential to be linked by ester linkages with each other or with other compounds. Ro 23-9424 is a novel compound in which the microbiologically active cefotaxime metabolite desacetyl-cefotaxime is linked by an ester bond at the C-3 position to the carboxy group of the quinolone fleroxacin. Initial studies showed that Ro 23-9424 combines the antibacterial spectrum and potency of both desacetyl-cefotaxime and fleroxacin (2, 4). This study was designed to determine the activity of this compound against a number of different species of bacteria and to compare its activity with those of cefotaxime, desacetylcefotaxime, fleroxacin, and two other fluoroquinolone compounds. MATERIALS AND METHODSAntibiotics. Ro 23-9424, fleroxacin, and desacetyl-cefotaxime were obtained from Hoffmann-La Roche Inc., Nutley, N.J. Cefotaxime was obtained from Hoechst-Roussel Pharmaceuticals Inc., Somerville, N.J. Ofloxacin was obtained from Ortho Pharmaceutical Corp., Raritan, N.J.; and ciprofloxacin was obtained from Miles Pharmaceuticals, West Haven, Conn. All other agents were obtained from their manufacturers.Organisms. Bacterial strains were obtained over a period of 1 year from patients who were hospitalized in the Columbia University hospital system in New York City. Antimicrobial susceptibility tests. MICs were determined with Mueller-Hinton agar for staphylococcal and gramnegative aerobic species. Activity against streptococcal species was determined with Mueller-Hinton agar supplemented with 5% sheep blood. Activity against Haemophilus and Neisseria species was determined with Mueller-Hinton chocolate agar, to which IsoVitaleX (BBL Microbiology Systems, Cockeysville, Md.) was added, with incubation done in 5% CO2. Activity against Bacteroides species and other anaerobic species was determined with brucella agar supplemented with 5% laked sheep blood and vitamin K. A final inoculum of 104 CFU, which was prepared by dilution of a fresh overnight broth culture, was applied to the agar with a replicate inoculating device according to guidelines of the National Committee for Clinical Laboratory Standards (6). Broth dilution was performed with an inoculum of 5 x 105 CFU/ml in a volume of 1 ml. Incubation took place at 35°C for 18 to 20 h; however, anaerobic organisms were incubated for 48 h. The MIC was defined as the lowest conce...

Relationship between structure and convulsant properties of some beta-lactam antibiotics following intracerebroventricular microinjection in rats

“…Several investigators found that the ability of penicillin derivatives to produce a seizure focus was abolished after incubation with penicillinase (12,15,16). Since these studies support the idea that the ␤-lactam ring is an indispensable structural feature for epileptogenic activity of penicillins and cephalosporins, we decided to include in our study aztreonam, a monobactam, as well as two carbapenem compounds, imipenem and meropenem, and Ro 23-9424, made up of desacetyl-cefotaxime linked to fleroxacin (14). In order to make a more accurate comparison of the convulsant activities of different ␤-lactam antibiotics, all compounds were administered intracerebroventricularly (i.c.v.).…”

Pharmacokinetics of Ro 23-9424, a dual-action cephalosporin, in animals

“…Ro 23-9424 has broad and potent antibacterial activity in vitro (2,9,12) and in vivo (3). The antibacterial spectrum reflects contributions of both the cephalosporin moiety (notably, streptococci) and the quinolone moiety (notably, ,-lactamase-overproducing strains).…”

Anti-<i>Brucella</i> Activity of Ro 23-9424, a Dual-Action Antibacterial

“…Although the range of MIC for Ro 23-9424 against our iso lates of B. melitensis was higher than that of ci profloxacin or fleroxacin, the ciprofloxacinresistant and fleroxacin-resistant isolates (MIC >8.0 mg/1) were susceptible to Ro 23-9424 with an MIC of 4.0 mg/1. Earlier reports have also shown that MIC values of Ro 23-9424 against many clinical isolates, including intracellular pathogens like Salmonella and Listeria, were higher than those for the com ponent drugs fleroxacin and ceftazidime [14][15][16]. This probably results from the com bined weight of the component drugs of Ro 23-9424.…”