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Journal of Antimicrobial Chemotherapy (1988) 22, 155-165
© 1988 The British Society for Antimicrobial Chemotherapy

research-article

In-vitro activity and ß-lactamase stability of LY163892

C. Caob, N. X. China and H. C. Neua,b

aDepartments of Medicine, College of Physicians & Surgeons, Columbia University New York, NY 10032, USA bDepartments of Pharmacology, College of Physicians & Surgeons, Columbia University New York, NY 10032, USA

Received 8 December 1987; accepted 22 February 1988

LY163892 is a new orally absorbed carbacephem. It inhibited Streptococcus pyogenes and Str. pneumoniae at ≤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 >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 ß-lactamases. For TEM-l, the Km = 354.7 µM, 25 Vmax = 2.5 µMoles/min/mg of protein, P99 Km = 24.3 µM, Vmax =28.9 µM/min/ug of protein, Staph. aureus PC Km = 47.4 µM, Vmax = 2.7 µMoles/min/mg of protein. Overall it had ß-lactamase stability similar to cefaclor, less than cephalexin, and markedly less than cefuroxime.


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