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% of Staphylococcus aureus and Staphylococcus epidermidis, including methicillin-resistant isolates at less than or equal to 1 microgram/ml. Its activity was comparable to those of vancomycin and teicoplanin. MIC90s for the beta-hemolytic streptococci varied from 0.25 microgram/ml for group B streptococci to 4 micrograms/ml for some group C and F streptococci. MICs for Streptococcus faecalis were in the range of 0.5 to 8 micrograms/ml, and the MIC90 4 micrograms/ml, compared to 4 micrograms/ml for vancomycin and 1 microgram/ml for teicoplanin. For some viridans streptococci the MICs were 4 micrograms/ml, whereas Streptococcus pneumoniae were inhibited by 0.5 microgram/ml. Corynebacterium JK species were inhibited by 0.5 microgram/ml, similar to vancomycin, and Listeria monocytogenes by 4 micrograms/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 sub-inhibitory concentrations of LY146032, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus faecalis showed minimal increase in MICs. The activity of LY146032 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.