Fukuoka T, Kawada H, Kitayama A, Koga T, Kubota M, Harasaki T, Kamai Y, Ohya S, Yasuda H, Iwata M, Kuwahara S
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Antimicrob Agents Chemother. 1998 Jan;42(1):23-7. doi: 10.1128/AAC.42.1.23.
The efficacy of CS-834, a novel oral carbapenem, was assessed by using a murine model of pneumonia caused by penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae and was compared with those of oral cephems, i.e., cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil. Intranasal inoculation of 10(6) CFU of penicillin-susceptible or penicillin-resistant S. pneumoniae in the exponential growth phase induced pneumonia and bacteremia in ddY mice within 48 h. For the treatment of infections caused by the penicillin-susceptible strain the antibiotics were administered orally at 0.4, 2, and 10 mg/kg of body weight twice daily for 2 days beginning at 24 h after bacterial inoculation, and for the treatment of infections caused by a penicillin-resistant strain the antibiotics were administered at 2, 10, and 50 mg/kg twice daily for 2 days beginning at 24 h after bacterial inoculation. Among the antibiotics tested, CS-834 exhibited the most potent efficacy against both types of strains. Against infections caused by penicillin-susceptible S. pneumoniae, CS-834 at all doses significantly reduced the numbers of viable cells in both the lungs and blood. Cefpodoxime proxetil at all doses and cefteram pivoxil and cefditoren pivoxil at doses of 2 and 10 mg/kg showed comparable efficacies. Against infections caused by penicillin-resistant S. pneumoniae, CS-834 at doses of 10 and 50 mg/kg showed the most potent efficacy among the antibiotics tested, resulting in the maximum decrease in the numbers of viable cells in the lungs. Comparable efficacies were observed with cefteram pivoxil and cefpodoxime proxetil at doses of 50 mg/kg each. The concentration of CS-834 in the lungs and blood was higher than that of cefdinir and was lower than those of the other antibiotics tested, suggesting that the potent therapeutic efficacy of CS-834 reflects its strong activity against S. pneumoniae.
采用对青霉素敏感和耐药的肺炎链球菌所致小鼠肺炎模型，评估新型口服碳青霉烯类药物CS - 834的疗效，并与口服头孢菌素类药物（头孢特仑新戊酯、头孢泊肟酯、头孢地尼和头孢妥仑匹酯）进行比较。在指数生长期经鼻接种10(6) CFU对青霉素敏感或耐药的肺炎链球菌，可在48小时内诱导ddY小鼠发生肺炎和菌血症。对于由青霉素敏感菌株引起的感染，从细菌接种后24小时开始，抗生素按0.4、2和10 mg/kg体重口服，每日两次，共2天；对于由青霉素耐药菌株引起的感染，从细菌接种后24小时开始，抗生素按2、10和50 mg/kg口服，每日两次，共2天。在所测试的抗生素中，CS - 834对两种菌株均表现出最强的疗效。对于由青霉素敏感的肺炎链球菌引起的感染，所有剂量的CS - 834均显著降低了肺和血液中的活菌数量。所有剂量的头孢泊肟酯以及2和10 mg/kg剂量的头孢特仑新戊酯和头孢妥仑匹酯显示出相当的疗效。对于由青霉素耐药的肺炎链球菌引起的感染，10和50 mg/kg剂量的CS - 834在所测试的抗生素中表现出最强的疗效，导致肺中活菌数量最大程度减少。50 mg/kg剂量的头孢特仑新戊酯和头孢泊肟酯观察到相当的疗效。CS - 834在肺和血液中的浓度高于头孢地尼，低于所测试的其他抗生素，这表明CS - 834强大的治疗效果反映了其对肺炎链球菌的强大活性。
