Influence of VanD type resistance on activities of glycopeptides in vitro and in experimental endocarditis due to Enterococcus faecium.

Abstract

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 microg/ml; teicoplanin, 4 microg/ml) and its susceptible derivative BM4459 (MICs: vancomycin, 1 microg/ml; teicoplanin, 1 microg/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.

• Authors: Agnès Lefort, Louis Garry, Florence Depardieu, Patrice Courvalin, Bruno Fantin
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 47 Issue 11 Pg. 3515-8 (Nov 2003) ISSN: 0066-4804 [Print] United States
• PMID: 14576110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Glycopeptides
• Teicoplanin
• Vancomycin
• Peptide Synthases
• VanD protein, Enterococcus faecium

Topics

• Animals
• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Bacterial Proteins (genetics)
• Drug Resistance, Bacterial
• Endocarditis (drug therapy, microbiology)
• Enterococcus faecium (drug effects)
• Female
• Glycopeptides (pharmacology, therapeutic use)
• Gram-Positive Bacterial Infections (drug therapy, microbiology)
• Heart Valves (microbiology)
• Microbial Sensitivity Tests
• Mutation (genetics)
• Peptide Synthases (genetics)
• Rabbits
• Teicoplanin (pharmacology, therapeutic use)
• Vancomycin (pharmacology, therapeutic use)