Antimicrobial activity of SK&F 88070, an expanded-spectrum cephalosporin with high and prolonged levels in blood.
SK&F 88070 (7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-3- [[[1-(2-sulfaminoethyl)-1H-tetrazol-5-yl]thio] methyl]-3-cephem-4-carboxylic acid) is a new parenteral cephalosporin with an expanded-spectrum profile of antibacterial activity, including activity against Pseudomonas aeruginosa, and with high and prolonged levels in sera of experimental animals. The activity of SK&F 88070 was compared with those of cefotaxime and other cephalosporins against more than 500 clinical isolates in vitro by microtiter twofold dilution tests in Mueller-Hinton broth. SK&F 88070 was extremely potent against all of the members of the family Enterobacteriaceae that were tested, including beta-lactamase-producing strains. Its activity against P. aeruginosa was comparable to those of cefotaxime, ceftizoxime, and moxalactam. SK&F 88070 was less potent than cefotaxime or ceftizoxime against Staphylococcus species but was comparable to moxalactam. It had in vivo activity against the same Bacteroides strains as did cefotaxime, although it was less potent. Both SK&F 88070 and cefotaxime had less activity when tested with high inoculum levels of most of the rarer gram-negative bacteria. There was a greater decrease in the activity of SK&F 88070 than of cefotaxime in the presence of human serum, reflecting the higher degree of binding of SK&F 88070 to serum proteins. SK&F 88070 had peak levels and half-lives in serum much greater than those of cefotaxime in experimental animals after parenteral administration. In mouse protection studies, SK&F 88070 was more effective than cefotaxime against gram-negative bacteria but less effective than cefotaxime against Staphylococcus aureus.
D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D001798:Blood Proteins / Q000378:metabolism; D015281:Cefmenoxime / Q000031:analogs & derivatives*; D002511:Cephalosporins / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D051379:Mice; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012453:Saimiri
D001798:Blood Proteins; D002511:Cephalosporins; C041591:SK&F 88070; D015281:Cefmenoxime