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	M Hikida, K Itahashi, A Igarashi, T Shiba, M Kitamura
Journal	Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 43 Issue 8 Pg. 2010-6 (Aug 1999) ISSN: 0066-4804 [Print] United States
PMID	10428928 (Publication Type: Comparative Study, Journal Article)
Chemical References	Anti-Bacterial Agents Anti-Infective Agents Bacterial Proteins Carbapenems Carrier Proteins Cephalosporins Escherichia coli Proteins LJC 11036 Lactams Penicillin-Binding Proteins Thienamycins beta-Lactams Levofloxacin Imipenem L 084 Ofloxacin Cefdinir Peptidyl Transferases Hexosyltransferases Peptidoglycan Glycosyltransferase penicillin-binding protein 1B, E coli Dipeptidases dipeptidase Serine-Type D-Ala-D-Ala Carboxypeptidase Muramoylpentapeptide Carboxypeptidase beta-Lactamases fropenem
Topics	Anti-Bacterial Agents (pharmacology) Anti-Infective Agents (pharmacology) Bacterial Proteins Carbapenems (pharmacokinetics, pharmacology) Carrier Proteins (metabolism) Cefdinir Cephalosporins (pharmacology) Dipeptidases (biosynthesis, metabolism) Drug Stability Escherichia coli Proteins Hexosyltransferases Imipenem (pharmacology) Lactams Levofloxacin Microbial Sensitivity Tests Muramoylpentapeptide Carboxypeptidase (metabolism) Ofloxacin (pharmacology) Penicillin-Binding Proteins Peptidoglycan Glycosyltransferase Peptidyl Transferases Protein Binding Serine-Type D-Ala-D-Ala Carboxypeptidase Thienamycins (pharmacology) beta-Lactamases (biosynthesis, metabolism) beta-Lactams

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