In vitro and in vivo antibacterial activities of CS-834, a novel oral carbapenem.

Abstract

CS-834 is a novel oral carbapenem antibiotic. This compound is an ester-type prodrug of the active metabolite R-95867. The antibacterial activity of R-95867 was tested against 1,323 clinical isolates of 35 species and was compared with those of oral cephems, i.e., cefteram, cefpodoxime, cefdinir, and cefditoren, and that of a parenteral carbapenem, imipenem. R-95867 exhibited a broad spectrum of activity covering both gram-positive and -negative aerobes and anaerobes. Its activity was superior to those of the other compounds tested against most of the bacterial species tested. R-95867 showed potent antibacterial activity against clinically significant pathogens: methicillin-susceptible Staphylococcus aureus including ofloxacin-resistant strains, Streptococcus pneumoniae including penicillin-resistant strains, Clostridium perfringens, Neisseria spp., Moraxella catarrhalis, most members of the family Enterobacteriaceae, and Haemophilus influenzae (MIC at which 90% of strains are inhibited, < or =0.006 to 0.78 microg/ml). R-95867 was quite stable to hydrolysis by most of the beta-lactamases tested except the metallo-beta-lactamases from Stenotrophomonas maltophilia and Bacteroides fragilis. R-95867 showed potent bactericidal activity against S. aureus and Escherichia coli. Penicillin-binding proteins 1 and 4 of S. aureus and 1Bs, 2, 3, and 4 of E. coli had high affinities for R-95867. The in vivo efficacy of CS-834 was evaluated in murine systemic infections caused by 16 strains of gram-positive and -negative pathogens. The efficacy of CS-834 was in many cases superior to those of cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil, especially against infections caused by S. aureus, penicillin-resistant S. pneumoniae, E. coli, Citrobacter freundii, and Proteus vulgaris. Among the drugs tested, CS-834 showed the highest efficacy against experimental pneumonia in mice caused by penicillin-resistant S. pneumoniae.

• Authors: T Fukuoka, S Ohya, Y Utsui, H Domon, T Takenouchi, T Koga, N Masuda, H Kawada, M Kakuta, M Kubota, C Ishii, C Ishii, E Sakagawa, T Harasaki, A Hirasawa, T Abe, H Yasuda, M Iwata, S Kuwahara
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 41 Issue 12 Pg. 2652-63 (Dec 1997) ISSN: 0066-4804 [Print] United States
• PMID: 9420035 (Publication Type: Journal Article)

Chemical References

• Bacterial Proteins
• Carbapenems
• Carrier Proteins
• Cephalosporins
• Penicillin-Binding Proteins
• Prodrugs
• R 95867
• Thienamycins
• Imipenem
• cefteram
• cefpodoxime
• cefditoren
• Ceftizoxime
• Peptidyl Transferases
• Hexosyltransferases
• Muramoylpentapeptide Carboxypeptidase
• beta-Lactamases
• CS 834
• Cefmenoxime

Topics

• Administration, Oral
• Animals
• Bacterial Infections (drug therapy, microbiology)
• Bacterial Proteins
• Carbapenems (pharmacology)
• Carrier Proteins (metabolism)
• Cefmenoxime (analogs & derivatives, pharmacology)
• Ceftizoxime (analogs & derivatives, pharmacology)
• Cephalosporins (pharmacology)
• Drug Stability
• Hexosyltransferases
• Imipenem (pharmacology)
• Mice
• Microbial Sensitivity Tests
• Muramoylpentapeptide Carboxypeptidase (metabolism)
• Penicillin-Binding Proteins
• Peptidyl Transferases
• Pneumonia, Staphylococcal (drug therapy, microbiology)
• Prodrugs (pharmacology)
• Thienamycins (pharmacology)
• beta-Lactamases (metabolism)