THE COMPARATIVE IN VITRO ACTIVITY AND β-LACTAMASE STABILITY OF A NEW UREIDO PENICILLIN

Abstract

The in vitro activity of Bay K-4999, 6[D-2-(3-furfurylidenamino-2-oxo-imidazolidine-1-carboxamido)-2-(4-hydroxy-phenyl) acetamido] penicillinate, a new ureido penicillin was evaluated against 555 clinical isolates and compared to selected β-lactams. Bay K-4999 inhibited most streptococci at concentrations less than I μg/ml, but was not active against β-lactamase producing Staphylococcus aureus. The activity of Bay K-4999 against streptococci including Streptococcus faecalis was similar to the activity of ampicillin. β-Lactamase-producing Haemophilus influenzae and Neisseria gonorrhoeae were inhibited by Bay K-4999; albeit at levels higher than needed for non-β-lactamasep roducing isolates. The activity of Bay K-4999 against the members of the Enterobacteriaceae varied from family to family and seemed to correlate with the presence of β-lactamases. Bay K-4999 was more active than ampicillin, piperacillin or mezlocillin against Escherichia coli lacking β-lactamases. It was more active against Klebsiella than piperacillin or mezlocillin, but cefazolin-resistant strains were not inhibited. It had activity against Pseudotonas aeruginosa comparable to piperacillin but was less active against Bacteroides fragilis. Bay K-4999 was hydrolyzed by β-lactamases of S. aureus, and by both plasmid and chromosomally-mediated β-lactamases of Enterobacteriaceae at rates comparable to ampicillin. It acted synergistically with gentamicin to inhibit resistant Pseudomonas isolates.