In vitro antibacterial activity of LJC 11,036, an active metabolite of L-084, a new oral carbapenem antibiotic with potent antipneumococcal activity

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 Strepto coccus pneumoniae (n = 52), Streptococcus pyogenes (n = 19), Haemophilus in fluenzae (n = 50), Klebsiella pneumoniae (n = 53), and Moraxella catarrhali s (n = 53), and from urinary-tract infections, such as Escherichia call (n = 53) (MICs at which 90% of the isolates were inhibited [MIC(90)s], 0.1, le ss than or equal to 0.006, 0.39, 0.05, 0.05, and 0.05 mu g/ml, respectively ), were 2- to 64-fold higher than those of imipenem, cefdinir, and faropene m. 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 levofloxaci n. WC 11,036 showed bactericidal activity equal or superior to that of imip enem. Bactericidal activity against penicillin-resistant S. pneumoniae (PRS P) did not vary with the phase of growth. LJC 11,036 had potent activity ag ainst various beta-lactamase-producing strains, excluding carbapenemase pro ducers. Against renal dehydropeptidase-I, WC 11,036 was more stable than im ipenem. Furthermore, LJC 11,036 produced in vitro postantibiotic sub-MIC ef fects against PRSP HSC-3 (6.0 h at one-fourth the MIC) and H. influenzae LJ 5 (9.2 h at one-half the MIC). LJC 11,036 showed high binding affinities fo r PBP1A, -1B, -2A/2X, -2B, and -3 of PRSP and for PBP1B, -2, -3A, and -3B o f H. influenzae.