In vitro and in vivo antibacterial activities of ER-35786, a new antipseudomonal carbapenem

Antimicrob Agents Chemother. 1997 Feb;41(2):298-307. doi: 10.1128/AAC.41.2.298.

Abstract

ER-35786 is a new parenteral 1 beta-methyl carbapenem with a broad antibacterial spectrum and a potent antipseudomonal activity. It showed high in vitro activity, comparable to those of meropenem and a new carbapenem, BO-2727, against methicillin-susceptible Staphylococcus aureus and streptococci, with MICs at which 90% of strains tested are inhibited (MIC90S) of < or = 0.39 microgram/ml. Against methicillin-resistant S. aureus, ER-35786 was the most active among the compounds tested, yet its MIC90 was 12.5 micrograms/ml. Against members of the family Enterobacteriaceae, Moraxella catarrhalis, and Haemophilus influenzae, ER-35786 inhibited 90% of strains tested at a concentration of < or = 1.56 micrograms/ml. The MIC90 of ER-35786 for Pseudomonas aeruginosa was 3.13 micrograms/ml, and the compound was more active than meropenem. In addition, the activity of ER-35786 against imipenem-, meropenem-, cefclidin-, or ceftazidime-resistant P. aeruginosa was equal to or higher than that of the most active reference compound. The in vivo activity of ER-35786 was consistent with this in vitro activity. The in vivo activity of ER-35786 was highest for systemic infection models with methicillin-resistant S. aureus and beta-lactam-resistant P. aeruginosa strains. In acute pneumonia caused by P. aeruginosa, ER-35786 produced a greater reduction in the viable cell count in the lungs than did imipenem-cilastatin or meropenem.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacteria / drug effects*
  • Bacteria / enzymology
  • Bacteria / isolation & purification
  • Bacterial Infections / drug therapy*
  • Carbapenems / metabolism
  • Carbapenems / pharmacology*
  • Carbapenems / therapeutic use
  • Dipeptidases / metabolism
  • Drug Resistance, Multiple
  • Humans
  • Kidney / enzymology
  • Male
  • Methicillin Resistance
  • Mice
  • Mice, Inbred ICR
  • Microbial Sensitivity Tests
  • Pneumonia, Bacterial / drug therapy
  • Pseudomonas Infections / drug therapy
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / isolation & purification
  • Pyrrolidines / metabolism
  • Pyrrolidines / pharmacology*
  • Pyrrolidines / therapeutic use
  • Swine
  • beta-Lactamases / metabolism

Substances

  • 6-(1-hydroxyethyl)-1-methyl-2-((pyrrolidin-3-yl-hydroxymethyl)pyrrolidin-4-ylthio)-1-carbapen-2-em-3-carboxylic acid hydrochloride
  • Anti-Bacterial Agents
  • Carbapenems
  • Pyrrolidines
  • Dipeptidases
  • dipeptidase
  • beta-Lactamases