title: In vitro antibacterial activity of LJC 11,036, an active metabolite of L-084, a new oral carbapenem antibiotic with potent antipneumococcal activity.
abstract: LJC 11,036 is the active metabolite of L-084, a novel oral carbapenem that exhibits potent broad-spectrum activity. Antibacterial activities of LJC 11,036 against clinical isolates from respiratory infections, such as Streptococcus pneumoniae (n = 52), Streptococcus pyogenes (n = 19), Haemophilus influenzae (n = 50), Klebsiella pneumoniae (n = 53), and Moraxella catarrhalis (n = 53), and from urinary-tract infections, such as Escherichia coli (n = 53) (MICs at which 90% of the isolates were inhibited [MIC(90)s], 0.1, </=0.006, 0.39, 0.05, 0.05, and 0.05 microg/ml, respectively), were 2- to 64-fold higher than those of imipenem, cefdinir, and faropenem. Moreover, against these bacterial species, except for H. influenzae, the MIC(90)s of LJC 11,036 were 4- to 512-fold lower than those of levofloxacin. LJC 11,036 showed bactericidal activity equal or superior to that of imipenem. Bactericidal activity against penicillin-resistant S. pneumoniae (PRSP) did not vary with the phase of growth. LJC 11,036 had potent activity against various beta-lactamase-producing strains, excluding carbapenemase producers. Against renal dehydropeptidase-I, LJC 11,036 was more stable than imipenem. Furthermore, LJC 11,036 produced in vitro postantibiotic sub-MIC effects against PRSP HSC-3 (6.0 h at one-fourth the MIC) and H. influenzae LJ5 (9.2 h at one-half the MIC). LJC 11,036 showed high binding affinities for PBP1A, -1B, -2A/2X, -2B, and -3 of PRSP and for PBP1B, -2, -3A, and -3B of H. influenzae.
authors.affiliation: Medical Research Laboratories, Lederle (Japan), Ltd., Shiki-shi, Saitama-ken 353-8511, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hikida
authors.forename: K
authors.initials: K
authors.lastname: Itahashi
authors.forename: A
authors.initials: A
authors.lastname: Igarashi
authors.forename: T
authors.initials: T
authors.lastname: Shiba
authors.forename: M
authors.initials: M
authors.lastname: Kitamura
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D001426:Bacterial Proteins; D015780:Carbapenems / Q000493:pharmacokinetics / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D000077525:Cefdinir; D002511:Cephalosporins / Q000494:pharmacology; D004150:Dipeptidases / Q000096:biosynthesis / Q000378:metabolism; D004355:Drug Stability; D029968:Escherichia coli Proteins; D006602:Hexosyltransferases; D015378:Imipenem / Q000494:pharmacology; D007769:Lactams; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D015242:Ofloxacin / Q000494:pharmacology; D046915:Penicillin-Binding Proteins; D046928:Peptidoglycan Glycosyltransferase; D010458:Peptidyl Transferases; D011485:Protein Binding; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D013845:Thienamycins / Q000494:pharmacology; D001618:beta-Lactamases / Q000096:biosynthesis / Q000378:metabolism; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D002352:Carrier Proteins; D002511:Cephalosporins; D029968:Escherichia coli Proteins; C120998:LJC 11036; D007769:Lactams; D046915:Penicillin-Binding Proteins; D013845:Thienamycins; D047090:beta-Lactams; D064704:Levofloxacin; D015378:Imipenem; C120999:L 084; D015242:Ofloxacin; D000077525:Cefdinir; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D046928:Peptidoglycan Glycosyltransferase; C478681:penicillin-binding protein 1B, E coli; D004150:Dipeptidases; C038937:dipeptidase; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases; C107057:fropenem