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 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-resistantStreptococcus pneumoniae , as well asNeisseria gonorrhoeae ,Moraxella catarrhalis , the members of the familyEnterobacteriaceae (with the exception ofSerratia marcescens ),Haemophilus influenzae , andBordetella pertussis ; for all these strains, the MICs at which 90% of tested strains are inhibited (MIC90 s) were 1.0 μg/ml or less. Against methicillin-resistant staphylococci, enterococci,Serratia marcescens ,Brukholderia cepacia ,Stenotrophomonas maltophilia , andAcinetobacter calcoaceticus , R-95867 showed activity comparable to or slightly less than that of imipenem, with MIC90 s ranging from 2 to >128 μg/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.