cefmenoxime and cefclidin

E1040 is a new parenteral cephalosporin with a broad antibacterial spectrum and potent activity against Gram-negative bacteria including Pseudomonas aeruginosa. The in-vitro activities of E1040 against clinical isolates of Enterobacter cloacae, Ent. aerogenes, Providencia rettgeri, and Morganella morganii were superior to those of ceftazidime, cefoperazone, cefmenoxime, and cefuzonam. The activities of E1040 against Gram-positive cocci were comparable with those of ceftazidime, but it was less active than cefmenoxime, cefuzonam, and cefoperazone. Against Ps. aeruginosa, E1040 was more potent than the other compounds, with an MIC90 of 0.39 mg/l, 1/16 that of ceftazidime. The in-vitro activity of E1040 was well sustained in vivo as shown by results obtained in experimental infections in mice. In particular, E1040 was the most active drug against Ps. aeruginosa including gentamicin-resistant and beta-lactamase-overproducing strains. Morphological studies using a scanning electron microscope and a phase-contrast microscope showed that E1040 caused spheroplast and bulge formation in Ps. aeruginosa at low concentrations.

Topics: Animals; Bacteria; Cefmenoxime; Cefoperazone; Ceftazidime; Ceftizoxime; Cephalosporins; Male; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Microscopy, Electron; Pseudomonas aeruginosa; Streptococcal Infections

E1040 is a new parenteral cephalosporin with a broad antibacterial spectrum and potent antipseudomonal activity. The compound was four- to eightfold more active than ceftazidime and cefsulodin against Pseudomonas aeruginosa (MIC of E1040 for 90% of strains tested [MIC90], 3.13 micrograms/ml). E1040 also showed a potent activity against other glucose-nonfermentative rods, including Acinetobacter species. The activities of E1040 against most species of the family Enterobacteriaceae were roughly comparable to the activities of ceftazidime and cefmenoxime and exceeded that of cefotiam. Against Citrobacter freundii (MIC90, 0.78 micrograms/ml), Enterobacter cloacae (MIC90, 3.13 micrograms/ml), and Enterobacter aerogenes (MIC90, 0.2 micrograms/ml), E1040 was 16- to 256-fold more active than ceftazidime and cefmenoxime. The activities of E1040 against gram-positive cocci and anaerobes were comparable to those of ceftazidime, but the compound was less active than cefmenoxime. E1040 was at least as resistant as ceftazidime and cefmenoxime to hydrolysis by various beta-lactamases and showed high affinities for penicillin-binding protein 3 of both Escherichia coli and P. aeruginosa.

Topics: Bacteria; Bacterial Proteins; beta-Lactamases; Carrier Proteins; Cefazolin; Cefmenoxime; Cefotaxime; Cefotiam; Cefsulodin; Ceftazidime; Cephalosporins; Escherichia coli Proteins; Hexosyltransferases; Humans; Methicillin; Muramoylpentapeptide Carboxypeptidase; Penicillin-Binding Proteins; Peptidoglycan Glycosyltransferase; Peptidyl Transferases; Protein Binding; Pseudomonas aeruginosa