title: In vitro activity of E-1040, a novel cephalosporin with potent activity against Pseudomonas aeruginosa.
abstract: The in vitro activity of E-1040 [(6R,7R)-3-[(4-carbamoyl-1-quinuclidinio)methyl]-7-[2-(5-amino-1,2 ,4- thiadiazol-3-yl)-(Z)-2-methoxyiminoacetoamido]-8-oxo-5-thia- 1- azabicyclo(4,2,0)oct-2-ene-2-carboxylate], a novel cephalosporin, was compared with that of ceftazidime, cefpirome, cefepime, imipenem, and gentamicin. E-1040 inhibited 50% of members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus and Neisseria species at less than or equal to 0.25 microgram/ml, and the MIC for 90% of strains tested ranged from 0.06 to 2 micrograms/ml. It was two- to fourfold more active than ceftazidime and similar in activity to cefepime and cefpirome. It inhibited Enterobacter, Citrobacter, Serratia, and Morganella species that were resistant to ceftazidime. E-1040 inhibited imipenem-, piperacillin-, aztreonam-, and tobramycin-resistant P. aeruginosa. It was less active against Xanthomonas maltophilia and P. cepacia but inhibited other Pseudomonas species. The activity of E-1040 against staphylococci and hemolytic streptococci was similar to that of ceftazidime, but E-1040 was less active than cefepime and cefpirome. It did not inhibit Bacteroides spp. There was no inoculum effect or medium effect, and MBCs were within a dilution of MICs. Plasmid beta-lactamases TEM-1, TEM-2, TEM-3 (CTX-1), SHV-1, Staphylococcus aureus, PSE, and CARB did not hydrolyze E-1040. Chromosomal beta-lactamases P99 and K-1 did not hydrolyze E-1040; E-1040 had poor affinity for these enzymes, with a Ki of greater than 100 microM.
authors.affiliation: Department of Medicine, College of Physicians & Surgeons, Columbia University, New York, New York 10032.
authors.forename: H C
authors.initials: HC
authors.lastname: Neu
authors.forename: N X
authors.initials: NX
authors.lastname: Chin
authors.forename: A
authors.initials: A
authors.lastname: Novelli
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D000077723:Cefepime; D002442:Ceftazidime / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology*; D004351:Drug Resistance; D004355:Drug Stability; D005839:Gentamicins / Q000494:pharmacology; D006868:Hydrolysis; D015378:Imipenem / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D001618:beta-Lactamases; D000097572:Cefpirome
chemical_list: D000617:Aminoglycosides; D000077723:Cefepime; D002442:Ceftazidime; D002511:Cephalosporins; D005839:Gentamicins; D015378:Imipenem; D001618:beta-Lactamases; D000097572:Cefpirome; C056494:cefclidin