Objective

We aim to describe the epidemiological, clinical and microbiological characteristics of the linezolid- and vancomycin- resistant Enterococcus faecium (LVRE) in a tertiary care hospital in Germany.

Methods

We conducted a retrospective analysis of 196 LVRE cases observed from 1st January 2012 to 31th December 2018. Patients’ medical charts were reviewed and available LVRE (n = 102) were subjected to whole-genome-sequencing. Antibiotic consumption was measured in defined daily dose (DDD)/100 bed-days (BD).

Results

The prevalence of LVRE isolates among VRE was 6.3 % in 2018. Most patients had an onco-hematological disease (134/196, 68.4 %). From 2012–2018 an increase of +356.7 % of linezolid defined daily dose/100 bed-days was observed. In 71.4 % (90/126, 70 missing values) of the patients, linezolid was prescribed in the previous 6 months. The median exposure to linezolid was 15 days (Interquartile, IQR 9–23). 42/196 (21.4 %) patients had an LVRE-related infection with an overall 30-day mortality rate of 33 %. In 121/196 (61.7 %) patients, linezolid-susceptible VREfm were isolated before LVRE, suggesting secondary acquisition of linezolid resistance. Genetic analysis revealed that most isolates belonged to ST117 (64/102 available isolates, 62.7 %). The G2576T 23S rDNA mutation was identified as the most common resistance mechanism (96/102, 94.1 %). poxtA was identified in two isolates, while cfr, and optrA were not detected.

Conclusions

Incidence of LVRE related to 23S rDNA mutations is rising and probably associated with antibiotic consumption. Restrictions in the use of linezolid may be needed in order to retain therapeutic options in VRE.

中文翻译：

---

耐万古霉素粪肠球菌ST117中耐线虫类药物的出现与线虫类药物的消费增加有关

目的

我们旨在描述德国一家三级医院的耐利奈唑胺和万古霉素的粪肠球菌（LVRE）的流行病学，临床和微生物学特征。

方法

我们对2012年1月1日至2018年12月31日期间观察到的196例LVRE病例进行了回顾性分析。回顾了患者的病历，并对可用的LVRE（n = 102）进行了全基因组测序。以规定的日剂量（DDD）/ 100床日（BD）测量抗生素的消耗量。

结果

2018年，VRE中LVRE分离株的患病率为6.3％。大多数患者患有肿瘤血液学疾病（134 / 196，68.4％）。从2012年至2018年，观察到+利奈唑胺确定的每日剂量/ 100床日增加了356.7％。在71.4％（90/126，70缺失值）的患者中，前6个月服用利奈唑胺。利奈唑胺的中位暴露时间为15天（四分位数，IQR 9-23）。42/196（21.4％）患者患有LVRE相关感染，其30天总死亡率为33％。在121/196（61.7％）患者中，利奈唑胺敏感性VRE fm在LVRE之前进行了分离，表明已获得了利奈唑胺抗性的二次获得。遗传分析表明，大多数分离株属于ST117（64/102个可用分离株，占62.7％）。G2576T 23S rDNA突变被确定为最常见的耐药机制（96 / 102，94.1％）。poxtA两种菌株经鉴定，而CFR，而OPTRA均未检出。

结论

与23S rDNA突变相关的LVRE发病率正在上升，可能与抗生素的使用有关。为了在VRE中保留治疗选择，可能需要限制使用利奈唑胺。