In-vitro activity and beta-lactamase stability of LY163892.
LY163892 is a new orally absorbed carbacephem. It inhibited Streptococcus pyogenes and Str. pneumoniae at less than or equal to 1 mg/l, but was less active against group B streptococci and groups C, F, G and bovis streptococci with MICs of 1 to 2 mg/l for most but as high as 8 mg/l for some isolates. MIC90 of methicillin-susceptible Staphylococcus aureus was 8 mg/l, but greater than 128 mg/l for methicillin-resistant staphylococci. LY163892 had activity similar to cefaclor and cephalexin with MIC90 values of 16 mg/l for Escherichia coli, 8 mg/l for Klebsiella pneumoniae, Proteus mirabilis, Yersinia enterocolitica, but was more active against Haemophilus influenzae, and Branhamella catarrhalis. It had no activity against Enterobacter, Providencia, Serratia, and Pseudomonas and Bacteroides spp. LY163892 was more rapidly lytic than cephalexin. It was hydrolyzed by a number of plasmid and chromosomal beta-lactamases. For TEM-1, the Km = 354.7 microM, Vmax = 2.5 microMoles/min/mg of protein, P99 Km = 24.3 microM, Vmax = 28.9 microM/min/micrograms of protein, Staph. aureus PC Km = 47.4 microM, Vmax = 2.7 microMoles/min/mg of protein. Overall it had beta-lactamase stability similar to cefaclor, less than cephalexin, and markedly less than cefuroxime.
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Department of Pharmacology, College of Physicians & Surgeons, Columbia University, New York, NY 10032.
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D000658:Amoxicillin / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D002473:Cell Wall / Q000502:physiology; D002511:Cephalosporins / Q000008:administration & dosage / Q000494:pharmacology*; D002969:Clavulanic Acids / Q000494:pharmacology; D004795:Enzyme Stability; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000378:metabolism*
D002511:Cephalosporins; D002969:Clavulanic Acids; C054920:loracarbef; D000658:Amoxicillin; D001618:beta-Lactamases