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Antimicrob Agents Chemother ; 41(2): 298-307, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9021183

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacterial Infections/drug therapy , Carbapenems/pharmacology , Pseudomonas aeruginosa/drug effects , Pyrrolidines/pharmacology , Animals , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/therapeutic use , Bacteria/enzymology , Bacteria/isolation & purification , Carbapenems/metabolism , 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/isolation & purification , Pyrrolidines/metabolism , Pyrrolidines/therapeutic use , Swine , beta-Lactamases/metabolism
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