Successful dissemination of resistance to oxazolidinones in multidrug-resistant Staphylococcus epidermidis clinical isolates

Due to patient- and procedure-related changes, coagulase negative staphylococci (CoNS) now represent one of the major nosocomial pathogens. Therapeutically, CoNS are challenging due to the large proportion of multidrug resistant strains. Thus, oxazolidinones are last resort antimicrobial molecules to treat CoNS infections. Using whole genome sequencing we have investigated a long-lasting outbreak (2004 to 2015) due to methicillin and linezolid-resistant (LR) CoNS (n=168), involving 72 carriers and 49 infected patients. This outbreak was caused by the dissemination of three main clones (ST2, ST5 and ST22) of LR Staphylococcus epidermidis. In these clones, the linezolid resistance was caused by (i) mutations in the chromosome-located genes encoding the 23S RNA and L3 and L4 ribosomal proteins, but also by (ii) the dissemination of two different self-conjugative plasmids carrying the cfr gene (encoding a 23S RNA methylase).