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Antimicrobial Agents and Chemotherapy, November 2003, p. 3515-3518, Vol. 47, No. 11
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.11.3515-3518.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Influence of VanD Type Resistance on Activities of Glycopeptides In Vitro and in Experimental Endocarditis Due to Enterococcus faecium

Institut National de la Santé et de la Recherche Médicale, EMI-U 9933, Hôpital Bichat-Claude Bernard,¹ Unité des Agents Antibactériens, Institut Pasteur, Paris, France²

Received 24 March 2003/ Returned for modification 5 June 2003/ Accepted 7 July 2003

The consequences of VanD type glycopeptide resistance on the activity of vancomycin and teicoplanin were evaluated in vitro and in a rabbit model of aortic endocarditis with VanD type clinical isolate Enterococcus faecium BM4339 (MICs: vancomycin, 64 µg/ml; teicoplanin, 4 µg/ml) and its susceptible derivative BM4459 (MICs: vancomycin, 1 µg/ml; teicoplanin, 1 µg/ml). The two antibiotics were inactive against BM4339 in vivo, in terms both of reduction of bacterial counts and of prevention of emergence of glycopeptide-resistant subpopulations, despite using teicoplanin at concentrations greater than the MIC for VanD strains. This could be due to the high inoculum effect also observed in vitro with BM4339 and two other VanD type isolates against both antibiotics. These results suggest that detection of VanD type resistance is of major importance because it abolishes in vivo glycopeptide activity and allows the emergence of mutants highly resistant to glycopeptides.

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