In vitro activity of LY264826, a new glycopeptide antibiotic, against gram-positive bacteria isolated from patients with cancer

The in vitro activity of LY264826, a novel glycopeptide antibiotic produced by Amycolatopsis orientalis, was compared with those of vancomycin, teicoplanin, and oxacillin against 311 gram-positive clinical isolates from patients with cancer. LY264826 had lower MICs for 90% of isolates (MIC₉₀) than vancomycin for all species tested. It was active against oxacillin-resistant isolates including Staphylococcus aureus (MIC₉₀, 0.5 μg/ml), Staphylococcus haemolyticus (MIC₉₀, 2.0 μg/ml), Enterococcus spp. (MIC₉₀, 0.5 μg/ml), Bacillus cereus (MIC₉₀, 0.25 μg/ml), and Corynebacterium jeikeium (MIC₉₀, 0.12 μg/ml). For S. aureus, including oxacillin-resistant isolates, the MICs of LY264826 were similar to those of teicoplanin. For coagulase-negative staphylococci, however, LY264826 had MICs that were 4- to 32-fold lower than those of teicoplanin. Against most streptococcal species the activities of LY264826 and teicoplanin were similar. Bactericidal activity against Staphylococcus spp. and most Streptococcus pyogenes isolates was ≤1 dilution of the MIC. One isolate of S. pyogenes and all Enterococcus faecalis strains tested were tolerant of LY264826, with MBCs ≥32-fold greater than the MICs. The addition of 50% human serum resulted in a significant increase in activity only against Staphylococcus epidermidis. Variations in pH from 6.4 to 8.4 and in inoculum from 10³ to 10⁷ CFU/ml did not significantly affect the activity of LY264826.