Antimicrobial activity of Ro 23-9424, a novel ester-linked codrug of fleroxacin and desacetylcefotaxime

Antimicrob Agents Chemother. 1989 Jun;33(6):944-50. doi: 10.1128/AAC.33.6.944.

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.

MeSH terms

  • Anti-Infective Agents*
  • Bacteria / drug effects*
  • Cefotaxime / analogs & derivatives*
  • Cefotaxime / pharmacology
  • Ciprofloxacin / analogs & derivatives*
  • Ciprofloxacin / pharmacology
  • Drug Combinations
  • Drug Resistance, Microbial
  • Fleroxacin
  • Fluoroquinolones*
  • Gram-Negative Aerobic Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Microbial Sensitivity Tests

Substances

  • Anti-Infective Agents
  • Drug Combinations
  • Fluoroquinolones
  • Ro-23-9424
  • Ciprofloxacin
  • desacetylcefotaxime
  • Cefotaxime
  • Fleroxacin