title: Antimicrobial activity of DU-6681a, a parent compound of novel oral carbapenem DZ-2640.
abstract: The in vitro antibacterial activity of DU-6681a, a parent compound of DZ-2640, against gram-positive and -negative bacteria was compared with those of penems and cephalosporins currently available. MICs at which 90% of the isolates are inhibited (MIC90s) of the compound for clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis, including methicillin-susceptible and -resistant strains, were 0.10, 25, and 12.5 microg/ml, respectively. DU-6681a inhibited the growth of all strains of Streptococcus pyogenes and of penicillin-susceptible and -insusceptible Streptococcus pneumoniae at 0.006, 0.025, and 0.20 microg/ml, respectively, and MIC90s of the compound were 6.25 and >100 microg/ml for Enterococcus faecalis and Enterococcus faecium, respectively. MIC90s of DU-6681a were 0.20, 0.10, and 0.025 microg/ml for Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, respectively. For Pseudomonas aeruginosa, the MIC50 and MIC90 of DU-6681a were 25 and 50 microg/ml, respectively. DU-6681a activity was not affected by different media, varied inoculum size (10(4) to 10(7) CFU), or the addition of human serum but was decreased under acidic conditions against gram-negative bacteria, under alkaline conditions against gram-positive bacteria, and in human urine, as was the activity of the other antibiotics tested. The frequency of spontaneous resistance to DU-6681a was less than or equal to those of the reference compounds. Time-kill curve studies demonstrated the bactericidal action of DU-6681a against S. aureus, S. pneumoniae, Escherichia coli, and H. influenzae.
authors.affiliation: New Product Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Hohmura
authors.forename: T
authors.initials: T
authors.lastname: Nishi
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: I
authors.initials: I
authors.lastname: Hayakawa
mesh_terms: D000284:Administration, Oral; D015780:Carbapenems / Q000494:pharmacology*; D004150:Dipeptidases / Q000378:metabolism; D004352:Drug Resistance, Microbial; D004795:Enzyme Stability; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D009154:Mutation; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D015780:Carbapenems; C106854:DU 6681; C106855:DZ 2640; D004150:Dipeptidases; C038937:dipeptidase; D001618:beta-Lactamases