title: In vitro and in vivo antibacterial activities of CS-834, a new oral carbapenem.
abstract: CS-834 is a prodrug of the carbapenem R-95867, developed by Sankyo Co., Ltd., Tokyo, Japan. To investigate the possibility that CS-834 may be the first carbapenem usable in an oral dosage form, its in vitro antibacterial activity (as R-95867) and in vivo antibacterial activity were compared with those of cefpodoxime proxetil, cefditoren pivoxil, cefdinir, ofloxacin, imipenem, and amoxicillin. R-95867 had high levels of activity against methicillin-susceptible staphylococci and streptococci, including penicillin-resistant Streptococcus pneumoniae, as well as Neisseria gonorrhoeae, Moraxella catarrhalis, the members of the family Enterobacteriaceae (with the exception of Serratia marcescens), Haemophilus influenzae, and Bordetella pertussis; for all these strains, the MICs at which 90% of tested strains are inhibited (MIC90s) were 1.0 microg/ml or less. Against methicillin-resistant staphylococci, enterococci, Serratia marcescens, Burkholderia cepacia, Stenotrophomonas maltophilia, and Acinetobacter calcoaceticus, R-95867 showed activity comparable to or slightly less than that of imipenem, with MIC90s ranging from 2 to >128 microg/ml. The in vivo efficacy of oral CS-834 against experimental mouse septicemia caused by gram-positive and gram-negative bacteria was better than that of comparative drugs. In murine respiratory infection models, the efficacy of CS-834 reflected not only its potent in vitro activity but also the high levels present in the lungs.
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan. keizo@sirius.med.toho-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: H
authors.initials: H
authors.lastname: Domon
authors.forename: S
authors.initials: S
authors.lastname: Miyazaki
authors.forename: K
authors.initials: K
authors.lastname: Tateda
authors.forename: A
authors.initials: A
authors.lastname: Ohno
authors.forename: K
authors.initials: K
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: N
authors.initials: N
authors.lastname: Furuya
mesh_terms: D000818:Animals; D015780:Carbapenems / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D015377:Cilastatin / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000097:blood / Q000188:drug therapy; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000097:blood / Q000188:drug therapy; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D011355:Prodrugs / Q000494:pharmacology* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000494:pharmacology; D018805:Sepsis / Q000097:blood / Q000188:drug therapy
chemical_list: D015780:Carbapenems; D011355:Prodrugs; D011480:Protease Inhibitors; D015377:Cilastatin; C107030:CS 834