Comparative In Vitro Activities of AC98-6446, a Novel Semisynthetic Glycopeptide Derivative of the Natural Product Mannopeptimycin α, and Other Antimicrobial Agents against Gram-Positive Clinical Isolates

Abstract

AC98-6446 is a novel semisynthetic cyclic glycopeptide antibiotic related to the natural product mannopeptimycin α (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 μg/ml). AC98-6446 also demonstrated good activities against both vancomycin-resistant and -susceptible strains of enterococci (MIC ₉₀ s, 0.12 and 0.25 μg/ml, respectively) as well as against streptococcal strains (MIC ₉₀ s, ≤ 0.008 to 0.03 μg/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.