Comparative in vitro activities of AC98-6446, a novel semisynthetic glycopeptide derivative of the natural product mannopeptimycin alpha, and other antimicrobial agents against gram-positive clinical isolates.
AC98-6446 is a novel semisynthetic cyclic glycopeptide antibiotic related to the natural product mannopeptimycin alpha (AC98-1). In the present study the activity of AC98-6446 was evaluated against a variety of recent clinical gram-positive pathogens including multiply resistant strains. AC98-6446 demonstrated similar potent activities against methicillin-susceptible and methicillin-resistant staphylococci and glycopeptide-intermediate staphylococcal isolates (MICs at which 90% of isolates are inhibited [MIC(90)s], 0.03 to 0.06 microg/ml). AC98-6446 also demonstrated good activities against both vancomycin-resistant and -susceptible strains of enterococci (MIC(90)s, 0.12 and 0.25 microg/ml, respectively) as well as against streptococcal strains (MIC(90)s, <or= 0.008 to 0.03 microg/ml). AC98-6446 demonstrated bactericidal activity in terms of the reduction in the viable counts (>3 log(10) CFU/ml) of staphylococcal and streptococcal isolates and a marked decrease in the viable counts of most enterococcal strains (from 0.2 to 2.5 log(10) CFU/ml). Unlike vancomycin, which demonstrates time-dependent killing, AC98-6446 demonstrated concentration-dependent killing. The potent activity, novel structure, and bactericidal activity demonstrated by AC98-6446 make it an attractive candidate for further development.
Petersen
Peter J
PJ
Infectious Disease Research, Microbiology, Wyeth Research, Pearl River, New York 10965, USA. petersp@wyeth.com
Wang
T Z
TZ
Dushin
Russell G
RG
Bradford
Patricia A
PA
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D013293:Enterococcus faecalis / Q000187:drug effects; D016984:Enterococcus faecium / Q000187:drug effects; D006020:Glycopeptides / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology*; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D014640:Vancomycin / Q000494:pharmacology
C483958:AC98-6446; D000900:Anti-Bacterial Agents; D006020:Glycopeptides; C478082:mannopeptimycin; D014640:Vancomycin