Naas Thierry, Fortineau Nicolas, Snanoudj Renaud, Spicq Colette, Durrbach Antoine, Nordmann Patrice
Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Sud, Université Paris IX, 78 rue du Général Leclerc 94275 Le Kremlin-Bicêtre Cedex, France.
J Clin Microbiol. 2005 Aug;43(8):3642-9. doi: 10.1128/JCM.43.8.3642-3649.2005.
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 microg/ml, whereas teicoplanin MICs ranged from 4 to 48 microg/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.
尽管在世界范围内，表达获得性万古霉素耐药表型的肠球菌报道日益增多，但在法国却鲜有报道。2004年8月至12月期间，我们在法国比塞特尔医院（K.-比塞特尔）的肾病科面临了一起耐万古霉素屎肠球菌（VRE）分离株的暴发。26株VRE分离株中糖肽类耐药的表达情况各不相同，万古霉素的最低抑菌浓度（MIC）范围为12至>256μg/ml，而替考拉宁的MIC范围为4至48μg/ml。然而，根据纸片扩散试验，有几株菌株似乎对糖肽类敏感，仅在糖肽类传代培养后才表现出耐药性。此外，还观察到糖肽类耐药的异质性表达。这种所谓的VanD样耐药表型（对万古霉素低水平耐药，对替考拉宁大多敏感）令人惊讶地与vanA基因相关。质粒提取和接合转移实验表明，vanA基因位于一个200kb的可自我转移的质粒上。脉冲场凝胶电泳显示主要是单一克隆的传播，而VanA阳性质粒也在不同的基因组背景中发生了扩散。vanA基因是位于Tn1546样转座子上的一个用于表达耐药性的vanA型操纵子的一部分。对该转座子进行测序发现，插入序列IS16插入到了编码d,d-羧肽酶的vanY基因中，这可能部分解释了这种特殊的VanD型耐药表型。本报告首次描述了法国的VRE暴发，并强调了由于糖肽类耐药性状表达的变异性（如果存在的话），检测这种微生物存在困难。
