Fukuoka T, Ohya S, Utsui Y, Domon H, Takenouchi T, Koga T, Masuda N, Kawada H, Kakuta M, Kubota M, Ishii C, Ishii C, Sakagawa E, Harasaki T, Hirasawa A, Abe T, Yasuda H, Iwata M, Kuwahara S
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Antimicrob Agents Chemother. 1997 Dec;41(12):2652-63. doi: 10.1128/AAC.41.12.2652.
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.
CS - 834是一种新型口服碳青霉烯类抗生素。该化合物是活性代谢产物R - 95867的酯型前体药物。对R - 95867针对35种的1323株临床分离菌的抗菌活性进行了测试，并与口服头孢菌素（即头孢特仑、头孢泊肟、头孢地尼和头孢妥仑）以及一种肠外碳青霉烯类药物亚胺培南的抗菌活性进行了比较。R - 95867展现出涵盖革兰氏阳性和阴性需氧菌及厌氧菌的广谱活性。其活性在针对大多数测试细菌种类时优于其他受试化合物。R - 95867对具有临床意义的病原体表现出强效抗菌活性：包括对氧氟沙星耐药菌株的甲氧西林敏感金黄色葡萄球菌、包括青霉素耐药菌株的肺炎链球菌、产气荚膜梭菌、奈瑟菌属、卡他莫拉菌、肠杆菌科的大多数成员以及流感嗜血杆菌（90%菌株被抑制时的最低抑菌浓度，≤0.006至0.78微克/毫升）。除了嗜麦芽窄食单胞菌和脆弱拟杆菌的金属β - 内酰胺酶外，R - 95867对大多数测试的β - 内酰胺酶的水解相当稳定。R - 95867对金黄色葡萄球菌和大肠杆菌表现出强效杀菌活性。金黄色葡萄球菌的青霉素结合蛋白1和4以及大肠杆菌的1Bs、2、3和4与R - 95867具有高亲和力。在由16株革兰氏阳性和阴性病原体引起的小鼠全身感染中评估了CS - 834的体内疗效。在许多情况下，CS - 834的疗效优于头孢特仑匹酯、头孢泊肟酯、头孢地尼和头孢妥仑匹酯，尤其是针对由金黄色葡萄球菌、青霉素耐药肺炎链球菌、大肠杆菌、弗氏柠檬酸杆菌和普通变形杆菌引起的感染。在所测试的药物中，CS - 834对青霉素耐药肺炎链球菌引起的小鼠实验性肺炎显示出最高疗效。
