In vitro activity of LY333328, a new glycopeptide, against extracellular and intracellular vancomycin-resistant enterococci

The objectives of the study were to observe the activity of LY333328, a new semisynthetic glycopeptide, compared to that of vancomycin against six strains of Enterococcus faecium and Enterococcus faecalis, including four vancomycin-resistant strains. Bacteria ingested by polymorphonuclear leukocytes (PMN) as well as extracellular bacteria were studied using a colony count method. The activity against intracellular bacteria was tested with the drugs present in the extracellular medium, as well as after preincubating the PMN and removal of the drugs. LY333328 is active against the tested enterococci, regard less of their susceptibility to vancomycin, with MICs of 1-2mg/l. It is bacteriostatic against extracellular enterococci at concentrations of 2 mu g/ml and above regardless of their resistance to vancomycin. After 4 h incubation at 10 MIC, vancomycin-resistant strains of E. faecium a nd E. faecalis located intracellularly were reduced by 55% and 90%, respectively. Even after preincubation and removal of the drug, LY333328 had an effect at 10 MIC with a 20-30% reduction in the inoculum. The results suggest that in contrast to vancomycin, LY333328 is active against intracellular vancomycin-resistant enterococci, particularly E. faecalis, even after removal of the extracellular drug.