Bender Jennifer, Strommenger Birgit, Steglich Matthias, Zimmermann Ortrud, Fenner Ines, Lensing Carmen, Dagwadordsch Urantschimeg, Kekulé Alexander S, Werner Guido, Layer Franziska
National Reference Centre for Staphylococci and Enterococci, Division of Nosocomial Pathogens and Antibiotic Resistances, Department of Infectious Diseases, Robert Koch Institute, Burgstraße 37, 38855 Wernigerode, Germany.
Institute of Medical Microbiology, University Medical Centre Göttingen, Kreuzbergring 57, 37075 Göttingen, Germany.
J Antimicrob Chemother. 2015;70(6):1630-8. doi: 10.1093/jac/dkv025. Epub 2015 Mar 3.
This study was a detailed investigation of Staphylococcus epidermidis clinical isolates exhibiting linezolid resistance.
Thirty-six linezolid-resistant S. epidermidis from eight German hospitals, including isolates from suspected hospital-associated outbreaks between January 2012 and April 2013, were analysed with respect to their antimicrobial susceptibility and the presence of cfr and/or mutations in the 23S rRNA, rplC, rplD and rplV genes. Relatedness of isolates was estimated by MLST and SmaI macrorestriction analysis. Characterization of cfr plasmids was carried out by means of Illumina sequencing.
The MICs of linezolid varied substantially between the isolates. No apparent correlation was detected between the level of resistance, the presence of cfr and ribosomal target site mutations. S. epidermidis isolates from two hospitals were confirmed as clonally related, indicating the spread of the respective clone over a period of 1 year. Next-generation sequencing revealed two different categories of cfr-expressing plasmids, both of them varying in genetic arrangement and composition from previously published cfr plasmids: p12-00322-like plasmids showed incorporation of cfr into a pGO1-like backbone and displayed capabilities for intra- and inter-species conjugational transfer.
To date, linezolid-resistant S. epidermidis have rarely been isolated from human clinical sources in Germany. Here, we describe the emergence and outbreaks of these strains. We detected previously described and novel point mutations in the 23S ribosomal genes. The cfr gene was only present in six isolates. However, this is the first known description of cfr incorporation into conjugative vectors; under selective pressure, these vectors could give reasonable cause for concern.
本研究对表现出对利奈唑胺耐药的表皮葡萄球菌临床分离株进行了详细调查。
分析了来自德国八家医院的36株对利奈唑胺耐药的表皮葡萄球菌，包括2012年1月至2013年4月疑似医院相关暴发的分离株，检测其抗菌药敏性以及cfr基因和/或23S rRNA、rplC、rplD和rplV基因中的突变情况。通过多位点序列分型（MLST）和SmaI宏限制性分析评估分离株的相关性。利用Illumina测序对cfr质粒进行表征。
分离株对利奈唑胺的最低抑菌浓度（MIC）差异很大。未检测到耐药水平、cfr基因的存在与核糖体靶位点突变之间存在明显相关性。来自两家医院的表皮葡萄球菌分离株被确认为克隆相关，表明相应克隆在1年内传播。新一代测序揭示了两类不同的表达cfr的质粒，它们在基因排列和组成上均与先前发表的cfr质粒不同：p12 - 00322样质粒显示cfr整合到pGO1样骨架中，并具有种内和种间接合转移能力。
迄今为止，德国很少从人类临床样本中分离出对利奈唑胺耐药的表皮葡萄球菌。在此，我们描述了这些菌株的出现和暴发情况。我们在23S核糖体基因中检测到了先前描述的和新的点突变。cfr基因仅在6株分离株中存在。然而，这是首次已知将cfr整合到接合载体中的描述；在选择性压力下，这些载体可能引发合理的担忧。
