Linezolid exposure of vancomycin-resistant Enterococcus faecium leads to nosocomial outbreaks of linezolid resistance

Linezolid is used as a first line treatment of vancomycin resistant Enterococcus (VRE) infection. Combined linezolid and vancomycin resistance cause treatment difficulties. The emergence of linezolid resistance in VRE is of concern. 492 E. faeicum (mostly VRE) from 447 patients were collected and whole-genome sequenced over a period of 8 years, 68 of which were in silico predicted to be linezolid-resistant (LinR). We compared LinR and linezolid susceptible (LinS) isolates with respect to MLST and determined core genome SNP differences. We also analyzed isolates from patients with longitudinal samples to identify whether patients carried a linR or linS isolate at the first sampling. We were able to demonstrate that linezolid exposure in combination with the high frequency of nosocomial transmissions of VRE pose a high risk for the spread of linezolid resistance in a hospital setting.