title: Newer antipseudomonal cephalosporins.
abstract: The in vitro antipseudomonal activity of eight cephalosporins with alpha-oxyimino-aminothiazolyl or aminothiadiazolyl group in the 7 beta-side chain and the quaternary ammonium moiety in the 3-position was evaluated. The order of antipseudomonal potency of these cephalosporins was as follows: cefaclidine > or = FK-518 > cefluprenam = cefozopran > or = ceftazidime > or = cefepime > cefpirome > or = cefoselis. Pseudomonas aeruginosa strains derepressed for the chromosomally mediated beta-lactamase (cephalosporinase) production were relatively susceptible to cefaclidine and FK-518, but were resistant to six other cephalosporins. P. aeruginosa strains producing the OXA-1-like penicillinase were resistant to cefaclidine, cefepime, and cefpirome, whose frequency was still lower. The higher antipseudomonal activity of these compounds than that of cefotaxime and some differences in activity among these compounds were suggested to result from cephalosporinase stability due to their low affinity for enzyme coupled with resistance to enzyme hydrolysis, assuming that the outer membrane permeation rates of compounds and their affinities for essential penicillin-binding proteins were almost the same. The aminothiadiazolyl cephalosporins showed higher antipseudomonal activity than the corresponding aminothiazolyl counterparts. This was also suggested to result from the same hypothesis as described above.
authors: Tsukuba Research Laboratories, Eisai Co., Ltd. Ibaraki, Japan.
authors: N A
authors: NA
authors: Watanabe
mesh_terms: D002510:Cephalosporinase / Q000378:metabolism; D002511:Cephalosporins / Q000737:chemistry / Q000494:pharmacology*; D006868:Hydrolysis; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D002511:Cephalosporins; D002510:Cephalosporinase; D001618:beta-Lactamases