Angehrn P, Probst P J, Reiner R, Then R L
Antimicrob Agents Chemother. 1980 Dec;18(6):913-21. doi: 10.1128/AAC.18.6.913.
Ro 13-9904, a new parenteral cephalosporin, was found to have high in vitro activity against Enterobacteriaceae and other gram-negative bacteria, including various isolates resistant to cefuroxime, cefamandole, cefoxitin, and cefazolin. It showed promising activity against Pseudomonas aeruginosa. Although inhibitory against Staphylococcus aureus at concentrations readily achievable in plasma, it was less potent against this pathogen than cefamandole, cefazolin, or cefuroxime. Isolates of Streptococcus faecalis were uniformly resistant to all the cephalosporins tested. Ro 13-9904 was more active than cefotaxime against Proteus mirabilis, Neisseria gonorrhoeae, Neisseria meningitidis, and Haemophilus influenzae, but less active against S. aureus. Ro 13-9904 was stable to various types of beta-lactamases. Its therapeutic efficacy against experimental septicemias in mice was equal to or slightly superior to that of cefotaxime and SCE-1365 when the antibiotics were administered in repeated subcutaneous doses after bacterial challenge. Cefoperazone, and particularly cefamandole nafate, cefazolin, and mezlocillin were less effective. Although structurally related to cefotaxime and SCE-1365, Ro 13-9904 was found to differ from them in one important respect, namely, in having a long duration of action; this was observed with single-dose treatment given before bacterial challenge. Its broad spectrum of activity coupled with favorable pharmacokinetic properties make Ro 13-9904 a promising compound for clinical studies.
Ro 13-9904是一种新型肠胃外头孢菌素,发现其对肠杆菌科细菌和其他革兰氏阴性菌具有很高的体外活性,包括对头孢呋辛、头孢孟多、头孢西丁和头孢唑林耐药的各种分离菌株。它对铜绿假单胞菌显示出有前景的活性。虽然在血浆中易于达到的浓度下对金黄色葡萄球菌有抑制作用,但对该病原体的效力低于头孢孟多、头孢唑林或头孢呋辛。粪肠球菌分离株对所有测试的头孢菌素均具有一致的耐药性。Ro 13-9904对奇异变形杆菌、淋病奈瑟菌、脑膜炎奈瑟菌和流感嗜血杆菌的活性比头孢噻肟高,但对金黄色葡萄球菌的活性较低。Ro 13-9904对各种类型的β-内酰胺酶稳定。在细菌攻击后以重复皮下剂量给药时,其对小鼠实验性败血症的治疗效果与头孢噻肟和SCE-1365相当或略优。头孢哌酮,尤其是头孢孟多酯钠、头孢唑林和美洛西林的效果较差。虽然Ro 13-9904在结构上与头孢噻肟和SCE-1365相关,但发现它在一个重要方面与它们不同,即具有较长的作用持续时间;这在细菌攻击前给予单剂量治疗时观察到。其广泛的活性谱加上良好的药代动力学特性使Ro 13-9904成为临床研究中一种有前景的化合物。