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Antimicrobial Agents and Chemotherapy, March 2004, p. 739-746, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.739-746.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Peter J. Petersen,^1* T. Z. Wang,² Russell G. Dushin,² and Patricia A. Bradford¹

Infectious Disease Research, Microbiology,¹ Chemical and Screening Sciences, Medicinal Chemistry, Wyeth Research, Pearl River, New York 10965²

Received 4 August 2003/ Returned for modification 9 November 2003/ Accepted 22 November 2003

AC98-6446 is a novel semisynthetic cyclic glycopeptide antibiotic related to the natural product mannopeptimycin (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 [MIC₉₀s], 0.03 to 0.06 µg/ml). AC98-6446 also demonstrated good activities against both vancomycin-resistant and -susceptible strains of enterococci (MIC₉₀s, 0.12 and 0.25 µg/ml, respectively) as well as against streptococcal strains (MIC₉₀s, 0.008 to 0.03 µg/ml). AC98-6446 demonstrated bactericidal activity in terms of the reduction in the viable counts (>3 log₁₀ 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 log₁₀ 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.

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* Corresponding author. Mailing address: Infectious Disease Research, Wyeth Research, Bldg. 200/Rm. 3301, 401 N. Middletown Rd., Pearl River, NY 10965. Phone: (845) 602-3070. Fax: (845) 602-5671. E-mail: petersp{at}wyeth.com.

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Antimicrobial Agents and Chemotherapy, March 2004, p. 739-746, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.739-746.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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