In vitro activity and spectrum of LY333328, a novel glycopeptide derivative

Reference methods were used to determine the potency of LY333328, a semisynthetic glycopeptide derivative with a key N-alkylation substitution, against 833 strains (393 gram-positive strains and representative gram-negative bacilli) with various defined resistance mechanisms. The MICs at which 90% of the isolates are inhibited (MIC90S) (in micrograms per milliliter) of LY333328 and the percentages of strains at < or = 8 micrograms/ml were as follows: for oxacillin-susceptible Staphylococcus aureus, 2 and 100%, and for oxacillin-resistant Staphylococcus aureus, 4 and 100%; for oxacillin-susceptible Staphylococcus epidermis, 4 and 100%, and for oxacillin-resistant Staphylococcus aureus, 8 and 96%; for Streptococcus serogroups A, B, C, and G, 0.25 to 1 and 100%; for Streptococcus pneumoniae < or = 0.015 to 0.06 and 100%; for Enterococcus faecalis, 2 and 100%; and for vancomycin-susceptible Enterococcus faecium, 0.25 and 100%, and for vancomycin-resistant Enterococcus faecium, 4 and 100%. LY333328 was not active (MIC50, > or = 16 micrograms/ml) against more than 400 representative strains of Enterobacteriaceae, pseudomonads, Acinetobacter spp., Stenotrophomonas maltophilia, Haemophilus influenzae, Moraxella catarrhalis, pathogenic Neisseria spp., and anaerobic gram-negative bacilli. Gram-positive anaerobes were LY333328 susceptible (MICs, < or = 2 micrograms/ml). Test methods and conditions may have affected MICs of LY333328, with most (species variation) agar dilution MICs being greater than the broth microdilution MICs.