In-vitro and in-vivo antibacterial activities of CS-834, a new oral carbapenem.
We evaluated the in-vitro and in-vivo antibacterial activities of R-95867 and CS-834, a new oral carbapenem which is an ester-type prodrug of R-95867. Against Gram-positive bacteria, R-95867 was as active or two to 256 times more active than cefpodoxime, cefdinir, cefditoren and ofloxacin, while its activity was similar to or two to eight times lower than that of imipenem. Against most Gram-negative bacteria it was as active or two to 1024 times more active than the other compounds tested. Against Helicobacter pylori it was two to 64 times more active than orally active anti-H. pylori agents, i.e. amoxycillin, clarithromycin and lansoprazole. It also showed potent bactericidal activity against Staphylococcus aureus and Escherichia coli. R-95867 induced a spherical form in E. coli and showed high affinity for PBP 2 in E. coli. Against systemic infections in mice caused by various bacteria, CS-834 showed an excellent protective effect and its in-vivo efficacy correlated well with the in-vitro activity of R-95867. These results suggest that CS-834 may be effective in the therapy of various bacterial infections.
Sakagawa
E
E
Department of Microbiology, Kyoto Pharmaceutical University, Yamashina, Japan.
Otsuki
M
M
Oh
T
T
Nishino
T
T
Ou
T
T
D000284:Administration, Oral; D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D001426:Bacterial Proteins; D015780:Carbapenems / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000378:metabolism; D015169:Colony Count, Microbial; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D006602:Hexosyltransferases; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D008857:Microscopy, Interference; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism; D010458:Peptidyl Transferases; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D011485:Protein Binding
D001426:Bacterial Proteins; D015780:Carbapenems; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D011355:Prodrugs; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; C107030:CS 834