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

Abstract

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.

Quinupristin/Dalfopristin Therapy for Infections Due to Vancomycin-Resistant Enterococcus faecium

“…These include linezolid, everninomicin, daptomycin, and LY333328 [45][46][47][48]. Each of these agents has activity against vancomycin-resistant E. faecium, which, in some cases (daptomycin, LY333328), is bactericidal, not just bacteriostatic.…”

Oritavancin: a novel lipoglycopeptide active against Gram-positive pathogens including multiresistant strains

“…In addition to effects on Gram-positive aerobes, oritavancin has proved active against Clostridium perfringens, Clostridium difficile, Peptostreptococcus spp. and Propionibacterium acnes [17].…”

“…Oritavancin shows potent activity against staphylococci, enterococci and streptococci, regardless of their resistance to antibiotics of the same class, and is even active against strains with a multiresistant phenotype [9][10][11][12][13][14][15][16][17]. Table 1 shows the interpretative criteria for minimum inhibitory concentration (MIC) susceptibility tests MIC, minimum inhibitory concentration.…”

Oritavancin: a new promising agent in the treatment of infections due to Gram-positive pathogens

“…Efficacy against all tested Clostridium pefringens, Clostridium difficile and Propionibacterium acnes has been demonstrated [124][125][126] . Against C. difficile two-to fourfold higher activity was found compared with vancomycin and metronidazole [127] .…”