Genomic and Phenotypic Analysis of Linezolid-Resistant Staphylococcus epidermidis in a Tertiary Hospital in Innsbruck, Austria.

Silke Huber,Katharina Mrazek,Viktoria Weber,Michael Ante,Andreas E Posch,Anita Brindlmayer,Sarah Lepuschitz,Michael Berktold,Dorothea Orth-Höller,Miriam A Knoll,Johannes Weinberger,Reinhard Würzner,Stephan Beisken

doi:10.3390/microorganisms9051023

Abstract

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 Staphylococcus epidermidis (LRSE, n = 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 (n = 91) was the major resistance mechanism followed by the presence of plasmid-derived cfr (n = 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 (n = 83) in most isolates, particularly in strains carrying the cfr gene (p < 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 cfr in LRSE are potential key steps to reduce linezolid resistance and its transmission to more pathogenic Gram-positive bacteria.

Highlights

Staphylococcus epidermidis is a commensal bacterium of humans, prevalent in skin and mucosa, emerging to frequently cause nosocomial and opportunistic infections [1,2]
At the Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, routinely isolated coagulase-negative Staphylococci (CoNS) from clinical samples were cryoconserved upon detection of linezolid resistance
Strains were primarily selected based on patient records indicating no prior administration of linezolid before isolation of a linezolid-resistant S. epidermidis (LRSE) (n = 48), and the remaining isolates were randomly selected for further analysis (n = 88)

Summary

Introduction

Staphylococcus epidermidis is a commensal bacterium of humans, prevalent in skin and mucosa, emerging to frequently cause nosocomial and opportunistic infections [1,2]. The clinical relevance of S. epidermidis has increased due to the bacteria’s ability to acquire and develop antimicrobial resistance (AMR) to a broad range of antibiotics and its capability of using horizontal gene transfer to disseminate AMR to the more pathogenic Staphylococcus aureus [3]. An oxazolidinone, is effective in a variety of Gram-positive strains; it is often the last-resort antibiotic for infections with multi drug resistant (MDR) Gram-positive cocci and was first approved in 2001 in Europe [4]. Linezolid-resistant S. epidermidis (LRSE) exhibits three main resistance mechanisms: (I)

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Conclusion