In vitro activity of LJC10,627, a new carbapenem antibiotic with high stability to dehydropeptidase I.
The in vitro activity of LJC10,627, a new carbapenem, was compared with those of imipenem and ceftazidime. LJC10,627 had broad-spectrum activity against gram-positive and gram-negative clinical isolates. The MICs of this compound for 90% of members of the family Enterobacteriaceae tested (MIC90s), including strains resistant to ceftazidime, ranged from 0.1 to 25 micrograms/ml. LJC10,627 inhibited Pseudomonas aeruginosa at an MIC90 of 3.13 micrograms/ml; it thus was twofold more active than imipenem. This compound inhibited Haemophilus, Neisseria, and Branhamella species at MIC90s of 3.13, 0.1, and 0.1 micrograms/ml, respectively. LJC10,627 was two- to fourfold less active than imipenem against methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis at MIC90s of 0.1 and 0.39 microgram/ml. However, the compound was found to be twofold more active than imipenem against Bacteroides fragilis at an MIC90 of 1.56 microgram/ml. LJC10,627 was very stable to various beta-lactamases except for Xanthomonas maltophilia oxyiminocephalosporinase type II. LJC10,627 was minimally hydrolyzed by swine renal dehydropeptidase I; its residual activity was 93.0% after 2 h. Killing kinetics of this compound for Escherichia coli and Pseudomonas aeruginosa showed that bactericidal action occurred at concentrations above the MIC (0.05 and 0.39 microgram/ml, respectively). LJC10,627 had a high affinity for penicillin-binding proteins 2, 4, and 1B(s) of Escherichia coli and Pseudomonas aeruginosa and penicillin-binding proteins 1 and 4 of Staphylococcus aureus.
Ubukata
K
K
Department of Clinical Pathology, Teikyo University School of Medicine, Tokyo, Japan.
Hikida
M
M
Yoshida
M
M
Nishiki
K
K
Furukawa
Y
Y
Tashiro
K
K
Konno
M
M
Mitsuhashi
S
S
D000818:Animals; D001426:Bacterial Proteins; D015780:Carbapenems / Q000378:metabolism / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D002442:Ceftazidime / Q000378:metabolism; D004150:Dipeptidases / Q000378:metabolism*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006602:Hexosyltransferases; D006868:Hydrolysis; D015378:Imipenem / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008858:Microscopy, Phase-Contrast; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011485:Protein Binding; D013552:Swine; D013845:Thienamycins; D001618:beta-Lactamases / Q000378:metabolism*
D001426:Bacterial Proteins; D015780:Carbapenems; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D013845:Thienamycins; D015378:Imipenem; D002442:Ceftazidime; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D004150:Dipeptidases; C038937:dipeptidase; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases; C065257:biapenem