Effect of growth phase and pH on the in vitro activity of a new glycopeptide, oritavancin (LY333328), against Staphylococcus aureus and Enterococcus faecium

Oritavancin (LY333328) is a novel glycopeptide with activity against Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. We compared the effects of pH and growth phase on the activity of oritavancin and vancomycin against methicillin-resistant S. aureus and vancomycin-susceptible and -resistant E. faecium. Killing curve methods were used to evaluate the effect of growth phase (stationary versus exponential) and pH (6.4, 7.4 and 8.0). An inoculum of 10(6) cfu/mL was used for all experiments. Growth phase of S. aureus and vancomycin-susceptible E. faecium did not influence the rate and killing activity of oritavancin. The rate of killing by oritavancin against the vancomycin-resistant E. faecium strain was significantly faster and the reduction in cfu/mL at 24 h was significantly greater when the organism was in exponential compared with stationary growth phase (P < 0.05). In exponential growth phase, time to 99.9% killing was achieved in 0.6 +/- 0.01 h for the vancomycin-resistant strain, whereas in stationary growth phase, oritavancin did not decrease the inoculum by 99.9% within 24 h. Oritavancin's activity against S. aureus and vancomycin-susceptible E. faecium was not influenced by the pH conditions tested. Oritivancin's killing activity against the vancomycin-resistant E. faecium strain was significantly enhanced when tested at pH 7.4 and 8.0 (P < 0.05). Our study has demonstrated that oritavancin's activity does not seem to be influenced by the growth phase of the organisms or the pH of the environment when tested against sensitive strains of S. aureus and E. faecium. However, oritavancin's activity might be reduced against vancomycin-resistant E. faecium strains in stationary growth phase, as seen in infective endocarditis or when organisms are exposed to an acidic environment.