The in-vitro activity of Ro 17-2301, a new monobactam, compared with other antimicrobial agents

Abstract

The susceptibility of 554 recent clinical isolates and known resistant bacterial strains to the new monocyclic β-lactam Ro 17–2301 were studied and compared to that to other β-lactams (including aztreonam and temocillin) and gentamicin. Ro 17–2301 had a high degree of activity against the Enterobacteriaceae (MIC₉₀≤ 0-25 mg/1) being similar or slightly more active than aztreonam and ceftaadime. Strains of Acinetobacter spp. (MIC₉₀ 16mg/l). Haemophilus influenzae strains (including β-lactamase producers) were more susceptible (MIC₉₀ 0 5 mg/1) than those of Neisseria gonorrhoeae (MIC₉₀ 4 mg/1); against these latter two groups of isolates aztreonam was more active (MIC₉₀ 0–12 mg/1). Both aztreonam and Ro 17–2301 had little activity against Gram-positive cocci with the exception of Streptococcus pneumoniae for which the MIC₉₀ of RO 17–2301 was 16 mg/1. Ro 17–2301 had modest activity against Bacteroidesfragilis. The MBC of Ro 17–2301 was very similar to the MIC and the addition of human serum had little effect on the amount of the compound The mean serum protein binding was 26.3% A study of the penicillin binding protein affinity of Ro 17–2301 in a strain of Escherichia coli showed PBP 3 to be the primary target. The morphological response to exposure to Ro 17–2301 was filamentation followed by lysis after prolonged exposure.