In Vitro Antibacterial Activity of LJC 11,036, an Active Metabolite of L-084, a New Oral Carbapenem Antibiotic with Potent Antipneumococcal Activity

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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 asEscherichia coli (n = 53) (MICs at which 90% of the isolates were inhibited [MIC90s], 0.1, ≤0.006, 0.39, 0.05, 0.05, and 0.05 μg/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 MIC90s 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 β-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) andH. 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.