Influence of VanD type resistance on activities of glycopeptides in vitro and in experimental endocarditis due to Enterococcus faecium.
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.
Institut National de la Santé et de la Recherche Médicale, EMI-U 9933, Hôpital Bichat-Claude Bernard. Unité des Agents Antibactériens, Institut Pasteur, Paris, France.
Agnès
A
Lefort
Louis
L
Garry
Florence
F
Depardieu
Patrice
P
Courvalin
Bruno
B
Fantin
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics*; D024881:Drug Resistance, Bacterial; D004696:Endocarditis / Q000188:drug therapy* / Q000382:microbiology*; D016984:Enterococcus faecium / Q000187:drug effects*; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006351:Heart Valves / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D010453:Peptide Synthases / Q000235:genetics*; D011817:Rabbits; D017334:Teicoplanin / Q000494:pharmacology / Q000627:therapeutic use; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006020:Glycopeptides; D017334:Teicoplanin; D014640:Vancomycin; D010453:Peptide Synthases; C122181:VanD protein, Enterococcus faecium