In-vitro activity of LY146032 against Staphylococcus aureus and S. epidermidis

The antibacterial activity of LY146032, a new cyclic polypeptide, was compared with that of vancomycin against 163 isolates of methicillin-susceptible and methicillin-resistant Staphylococcus aureus and S. epidermidis. The MICs of LY146032 and vancomycin for 90% of the isolates were 1.0 mg/l and 2.0-4.0 mg/l, respectively. Interpretative guidelines for 15 micrograms and 30 micrograms LY146032 discs could not be established because all isolates tested were susceptible to LY146032, on the basis of achievable serum levels. With one exception, MBC to MIC ratios of LY146032 and vancomycin were less than or equal to 2. Inoculum size had minimal effect on ratios. In time-kill studies, both drugs were 99.9% bactericidal at 6 h for four isolates at concentrations four times the MBC or less. No change in LY146032 activity was observed between isogenic pairs that were resistant to other antibiotics. Thus, LY146032 was very active in vitro against all staphylococcal isolates.