IN-VITRO AND IN-VIVO ANTIBACTERIAL ACTIVITIES OF CS-834, A NEW ORAL CARBAPENEM

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 h e the first carbapenem usable in an oral dosage form, its in vitro ant ibacterial activity (as R-95867) and in vivo antibacterial activity we re compared with those of cefpodoxime proxetil, cefditoren pivoxil, ce fdinir, ofloxacin, imipenem, and amoxicillin. R-95867 had high levels of activity against methicillin-susceptible staphylococci and streptoc occi, including penicillin-resistant Streptococcus pneumoniae, as well as Neisseria gonorrhoeae, Moraxella catarrhalis, the members of the f amily Enterobacteriaceae (with the exception of Serratia marcescens), Haemophilus influenzae, and Bordetella pertussis; for all these strain s, the MICs at which 90% of tested strains are inhibited (MIC(90)s) we re 1.0 mu g/ml or less. Against methicillin-resistant staphylococci, e nterococci, Serratia marcescens, Brukholderia cepacia, Stenotrophonoma s maltophilia, and Acinetobacter calcoaceticus, R-95867 showed activit y comparable to or slightly less than that of imipenem, with MIC,,s ra nging from 2 to >128 mu g/ml. The in vivo efficacy of oral CS-834 agai nst experimental mouse septicemia caused by gram-positive and gram-neg ative bacteria was better than that of comparative drugs. In murine re spiratory infection models, the efficacy of CS-834 reflected not only its potent in vitro activity but also the high levels present in the l ungs.