Comparative in-vitro activity of LY146032 a new peptolide, with vancomycin and eight other agents against gram-positive organisms

The in-vitro activity of LY146032, a new biosynthetic peptolide antibiotic, was compared with vancomycin and eight other antibiotics against 190 Gram-positive bacteria. Organisms tested included streptomycin-susceptible and resistant enterococci, nafcillin-susceptible and resistant Staphylococcus aureus, and nafcillin-susceptible and resistant Staph. epidermidis. LY146032 had excellent in-vitro inhibitory and bactericidal activity against nafcillin-susceptible and resistant staphylococci (MIC90 less than or equal to 0.5 mg/l) and against enterococci (MIC90 less than or equal to 2.0 mg/l). LY146032 was more active than vancomycin against the majority of isolated tested. With the exception of trimethoprim-sulphamethoxazole, LY146032 was the most active agent in vitro against enterococci, and was the most active against nafcillin-resistant staphylococci. LY146032 and vancomycin showed a marked increase in MIC when the inoculum was increased from 10(5) to 10(7) cfu/ml. LY146032 and vancomycin were bactericidal at concentrations within two dilutions of the MIC for staphylococci. LY146032 was bactericidal at less than or equal to 8 mg/l for all enterococcal isolates tested.