In vitro activity of LY146032 against gram-positive bacteria

Abstract

The activity of LY146032 (LY) was evaluated against 269 clinical isolates: 150 Staphylococcus spp. (Staph), 45 enterococci, 51 Clostridium spp., and 23 peptostreptococci. LY was compared to penicillin, metronidazole, imipenem, clindamycin, oxacillin, ciprofloxacin, vancomycin, and ampicillin. LY and oxacillin were tested against Staph by microdilution in cation-supplemented Mueller-Hinton broth (CSMHB), and in unsupplemented Mueller-Hinton broth (MHB). For LY, the MIC 90s in CSMHB were 16-32 dilutions lower. Among the Staph, the MIC 90s for LY, vancomycin, and ciprofloxacin were 4 micrograms/ml, 4 micrograms/ml, and 2 micrograms/ml respectively. The MIC 90s for enterococci by agar dilution were as follows: LY 8 micrograms/ml; ampicillin 4 micrograms/ml; imipenem 4 micrograms/ml; vancomycin 4 micrograms/ml; and ciprofloxacin 2 micrograms/ml. Clindamycin and penicillin were the most effective drugs against peptostreptococci and Clostridia spp., but LY was the most active drug against Clostridium difficile. The bactericidal activity of LY was determined by 24-hr time-kill curves in MHB. These showed a bactericidal effect against enterococci, and a bacteriostatic effect against three of four strains of Staph. Synergy was demonstrated against enterococci and Staph when LY was tested with aztreonam, ceftriaxone, or tobramycin. LY is a promising new agent against gram-positive bacteria, including methicillin resistant strains of staphylococci and enterococci.