In vitro activity of LY146032 (Daptomycin), a new peptolide

The in vitro activity of LY146032, a new peptolide antibiotic, was compared with those of vancomycin, teicoplanin, imipenem, amoxicillin and erythromycin. LY146032 inhibited 90% ofStaphylococcus aureus andStaphylococcus epidermidis, including methicillin-resistant isolates at 1g/ml. Its activity was comparableto those of vancomycin and teicoplanin. MIC90s for the beta-hemolytic streptococci varied from 0.25 g/ml for group B streptococci to 4g/ml for some group C and F streptococci. MICs forStreptococcus faecalis were in the range of 0.5 to 8 g/ml,and the MIC90 4 g/ml,compared to 4 g/ml for vancomycin and 1g/ml for teicoplanin. For some viridans streptococci the MICs were 4g/ml, whereasStreptococcus pneumoniae were inhibited by 0. 5g/ml.Corynebacterium JK species were inhibited by 0. 5g/ml, similar to vancomycin, andListeria monocytogenes by 4g/ml.Neisseria species,Haemophilus species and enteric species were not inhibited. Most MBCs were within two-fold of the respective MICs. After 14 days passage in subinhibitory concentrations of LY146032,Staphylococcus aureus, Staphylococcus epidermidis andStreptococcus faecalis showed minimal increase in MICs. The activity of LY 146032 was increased by adding Ca²⁺ and was reduced in an anaerobic environment. Overall, LY146032 is an extremely interesting new agent that inhibits gram-positive species.