Worldwide assessment of dalbavancin activity and spectrum against over 6,000 clinical isolates

Continuing emergence of new antimicrobial resistance mechanisms and the increased frequency of existing resistances, requires the development of alternative antimicrobial agents. Dalbavancin is an amide glycopeptide derivative with a markedly extended serum elimination half-life. Dalbavancin and selected comparators were tested against 6,339 recent clinical isolates (2002) from the Americas and Europe using reference susceptibility testing methods. The general characteristics of this Gram-positive organism collection were: oxacillin (OXA)-resistant Staphylococcus aureus (ORSA) at 39% of strains; vancomycin-resistant enterococci (VRE) at 10%; and penicillin-nonsusceptible pneumococci at 28%. The overall distribution of dalbavancin minimum inhibitory concentration (MIC) values ranged from less than or equal to0.015 to > 32 mug/ml, but > 99% of MIC results were at less than or equal to1 mug/ml. S. aureus and coagulase-negative staphylococci were extremely susceptible to dalbavancin (MIC90, 0.06 mug/ml) despite resistance patterns to other agents. Dalbavancin was the most potent compound (by weight) against vancomycin-susceptible Enterococcus faecalis and E faecium (MIC90, 0.06 and 0.12 mug/ml, respectively); however, VRE strains showed decreased dalbavancin susceptibility MIC50, 4 or 8 mug/ml). All streptococcal isolates were inhibited at less than or equal to0.25 mug/ml of dalbavancin. This reported dalbavancin activity indicates that the new glycopeptide has significant activity, superior to available agents in the class, and a potency that was uniform across geographically sampled organisms. Some VRE were inhibited by very low dalbavancin concentrations ( less than or equal to1 mug/ml; Van B phenotypes). Further clinical development seems warranted for this once-weekly administered agent. (C) 2004 Elsevier Inc. All rights reserved.