title: In vitro and in vivo antibacterial activities of ER-35786, a new antipseudomonal carbapenem.
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.
authors.affiliation: Department of Microbiology and Infectious Diseases, Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Ohba
authors.forename: M
authors.initials: M
authors.lastname: Nakamura-Kamijo
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Katsu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D001424:Bacterial Infections / Q000188:drug therapy*; D015780:Carbapenems / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004150:Dipeptidases / Q000378:metabolism; D018432:Drug Resistance, Multiple; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D018410:Pneumonia, Bacterial / Q000188:drug therapy; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D011759:Pyrrolidines / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D013552:Swine; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: C105416:6-(1-hydroxyethyl)-1-methyl-2-((pyrrolidin-3-yl-hydroxymethyl)pyrrolidin-4-ylthio)-1-carbapen-2-em-3-carboxylic acid hydrochloride; D000900:Anti-Bacterial Agents; D015780:Carbapenems; D011759:Pyrrolidines; D004150:Dipeptidases; C038937:dipeptidase; D001618:beta-Lactamases