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We tested the activity of LY146032 (LY) against 57 strains of enterococci collected from Chile, Thailand, and the United States. Some of the strains were resistant to high levels of gentamicin or streptomycin (or both), and two produced beta-lactamase (Bla+). MICs of LY ranged from 0.5 to 8 micrograms/ml, and MBCs ranged from 1 to 64 micrograms/ml. In time-kill assays, a 2 to 3 log10 killing effect was observed with LY against two Bla+ strains of Streptococcus (Enterococcus) faecalis and against three strains that were highly resistant to streptomycin and gentamicin. Synergism was demonstrated with LY and streptomycin against a Bla+ strain lacking high-level streptomycin resistance. These in vitro results suggest that LY should be studied further for possible use in treatment of enterococcal infections.

Activity of LY146032 against Enterococci with and without high-level aminoglycoside resistance, including two penicillinase-producing strains