| Summary: | Whole genome sequencing is a useful tool to monitor the spread of resistance mechanisms in bacteria. In this retrospective study, we investigated genetic resistance mechanisms, sequence types (ST) and respective phenotypes of linezolid-resistant <i>Staphylococcus epidermidis</i> (LRSE, <i>n</i> = 129) recovered from a cohort of patients receiving or not receiving linezolid within a tertiary hospital in Innsbruck, Austria. Hereby, the point mutation G2603U in the 23S rRNA (<i>n</i> = 91) was the major resistance mechanism followed by the presence of plasmid-derived <i>cfr</i> (<i>n</i> = 30). The majority of LRSE isolates were ST2 strains, followed by ST5. LRSE isolates expressed a high resistance level to linezolid with a minimal inhibitory concentration of ≥256 mg/L (<i>n</i> = 83) in most isolates, particularly in strains carrying the <i>cfr</i> gene (<i>p</i> < 0.001). Linezolid usage was the most prominent (but not the only) trigger for the development of linezolid resistance. However, administration of linezolid was not associated with a specific resistance mechanism. Restriction of linezolid usage and the monitoring of plasmid-derived <i>cfr</i> in LRSE are potential key steps to reduce linezolid resistance and its transmission to more pathogenic Gram-positive bacteria.
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