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Journal of Clinical Microbiology, August 2005, p. 3642-3649, Vol. 43, No. 8
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.8.3642-3649.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

First Nosocomial Outbreak of Vancomycin-Resistant Enterococcus faecium Expressing a VanD-Like Phenotype Associated with a vanA Genotype

Thierry Naas,1* Nicolas Fortineau,1 Renaud Snanoudj,2 Colette Spicq,1 Antoine Durrbach,2 and Patrice Nordmann1

Service de Bactériologie-Virologie,1 Service de Nephrologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Sud, Université Paris XI, 94275, K.-Bicêtre, France2

Received 15 February 2005/ Returned for modification 29 March 2005/ Accepted 9 April 2005

Although enterococci expressing acquired vancomycin resistance phenotype have been reported increasingly worldwide, they have been rarely reported in France. From August to December 2004 we faced an outbreak of vancomycin-resistant Enterococcus faecium (VRE) isolates in the nephrology department at Bicêtre Hospital (K.-Bicêtre, France). The expression of the glycopeptide resistance varied among the 26 VRE isolates, with vancomycin MICs ranging from 12 to >256 µg/ml, whereas teicoplanin MICs ranged from 4 to 48 µg/ml. However, several strains appeared to be susceptible to glycopeptides according to disk diffusion testing and expressed resistance only after subculture with glycopeptides. In addition, a heterogeneous expression of glycopeptide resistance was also observed. This so-called VanD-like phenotype of resistance (low-level resistance to vancomycin and mostly susceptibility to teicoplanin) was surprisingly associated with a vanA gene. Plasmid extraction and mating-out experiments indicated that the vanA gene was located on a 200-kb self-transferable plasmid. Pulsed-field gel electrophoresis identified mostly dissemination of a single clone, whereas diffusion of the VanA-positive plasmid in different genomic backgrounds had also occurred. The vanA gene was part of a vanA-type operon for expression of resistance located on a Tn1546-like transposon. Sequencing of this transposon identified insertion of insertion sequence IS16 in the vanY gene that encodes a D,D-carboxypeptidase that might explain in part the peculiar VanD-type phenotype of resistance. This report is the first description of a VRE outbreak in France and underlines the difficulty in detecting this organism due to variability on the expression of the glycopeptide resistance trait, if any.

* Corresponding author. Mailing address: Service de Bactériologie-Virologie, Hôpital de Bicêtre, 78 rue du Général Leclerc 94275 Le Kremlin-Bicêtre Cedex, France. Phone: 33-1-45-21-36-24. Fax: 33-1-45-21-63-40. E-mail: thierry.naas{at}bct.ap-hop-paris.fr.

Journal of Clinical Microbiology, August 2005, p. 3642-3649, Vol. 43, No. 8
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.8.3642-3649.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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