Comparative in-vitro activity of LY146032 and eight other antibiotics against gram-positive bacteria isolated from children

Abstract

LY146032, a cyclic peptide antibiotic active against many Gram-positive bacteria, was compared to methicillin, vancomycin, clindamycin, cefuroxime and gentamicin against methicillin-resistant and methicillin-susceptible strains of Staphylococcus aureus and Staph. epidermidis. LY146032 was uniformly active against clinical isolates of staphylococci, inhibiting 90% of strains of Staph. aureus and Staph. epidermidis at a concentration of 0.5 mg/l. Vancomycin was slightly less active than LY146032 against Staph. aureus and Staph. epidermidis, inhibiting 90% of strains at concentrations of 1.0 and 2.0 mg/l, respectively. All other antibiotics tested were less active than LY146032 or vancomycin against staphylococci. LY146032 was compared to penicillin, ampicillin, vancomycin and chloramphenicol against strains of Streptococcus pneumoniae, group B streptococcus, group D streptococcus (enterococcus) and Listeria monocytogenes and was found to inhibit 90% of the strains at concentrations of 0.25, 1.0, 32.0 and 16.0 mg/l respectively. The combination of LY146032 and chloramphenicol was antagonistic in vitro for one strain each of Staph. aureus and group D streptococcus and showed indifference against other strains of Staph. aureus(2), Staph. epidermidis(2), group D streptococcus(1) and L. monocytogenes(2). LY146032 in combination with gentamicin showed indifference against the same bacteria. On the basis of its in-vitro activity, LY146032 appears to be a promising agent for the treatment of serious community- and hospital-acquired staphylococcal infections.