title: Antimicrobial activity of Ro 23-9424, a novel ester-linked codrug of fleroxacin and desacetylcefotaxime.
abstract: Ro 23-9424 is a novel ester-linked codrug of fleroxacin (Ro 23-6240; AM-833) and the cefotaxime metabolite desacetylcefotaxime. Its potency was determined against over 1,000 organisms and found to be intermediate between those of the two components. More than 99% of members of the family Enterobacteriaceae were inhibited by greater than or equal micrograms of Ro 23-9424 per ml; its MIC for 50% of strains tested ranged from greater than or equal to 0.06 to 1 micrograms/ml. Staphylococci, streptococci, Branhamella catarrhalis, Corynebacterium jeikeium, Bacillus spp., Haemophilus influenzae, Listeria monocytogenes, and the pathogenic Neisseria spp., including oxacillin-resistant Staphylococcus aureus, beta-lactamase-producing strains, and penicillin-resistant pneumococci, were also inhibited by Ro 23-9424. Pseudomonas aeruginosa, Enterococcus spp., and Bacteroides fragilis group isolates were more refractory to Ro 23-9424 (the MIC for 90% of strains tested was less than or equal to 32 micrograms/ml). Overall, Ro 23-9424 inhibited 97% of the aerobic strains, compared with 90% for ceftazidime and 92% for cefoperazone. Ro 23-9424 was bactericidal, was relatively stable to inoculum effects on MICs at 10(7) CFU/ml, and was determined to be highly active against organisms resistant to fluoroquinolones or ceftazidime. Preliminary quality control guidelines were determined, and a 30-micrograms disk concentration appears to be the most usable form.
authors.affiliation: Clinical Microbiology Institute, Tualatin, Oregon 97062.
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
authors.forename: A L
authors.initials: AL
authors.lastname: Barry
authors.forename: C
authors.initials: C
authors.lastname: Thornsberry
mesh_terms: D000890:Anti-Infective Agents; D001419:Bacteria / Q000187:drug effects*; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000494:pharmacology; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004338:Drug Combinations; D004352:Drug Resistance, Microbial; D016576:Fleroxacin / Q000031:analogs & derivatives; D024841:Fluoroquinolones; D006088:Gram-Negative Aerobic Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests
chemical_list: D000890:Anti-Infective Agents; D004338:Drug Combinations; D024841:Fluoroquinolones; C060441:Ro-23-9424; D002939:Ciprofloxacin; C029281:desacetylcefotaxime; D002439:Cefotaxime; D016576:Fleroxacin