First outbreak of colonization by linezolid- and glycopeptide-resistant Enterococcus faecium harbouring the cfr gene in a UK nephrology unit

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Summary

Aim

To describe an outbreak of colonization by linezolid- and glycopeptide-resistant Enterococcus faecium harbouring the cfr gene in a UK nephrology unit.

Methods

Isolates of linezolid-resistant E. faecium were typed by pulsed-field gel electrophoresis (PFGE), and examined by polymerase chain reaction (PCR) and sequencing for the transmissible cfr gene that confers resistance to linezolid. Enhanced environmental cleaning, initial and weekly screening of all patients, and monitoring of adherence to standard infection control precautions were implemented.

Findings

Five patients with pre-existing renal disease were found to have rectal colonization with linezolid-resistant E. faecium over a two-week period. The index case was a 57-year-old male from India who had travelled to the UK. One patient also had a linezolid-resistant E. faecium of a different PFGE profile isolated from a heel wound. All isolates were confirmed to harbour the cfr gene by PCR and Sanger sequencing, and all were resistant to glycopeptides (VanA phenotype).

Conclusions

This article describes the first UK outbreak with a single strain of linezolid- and glycopeptide-resistant E. faecium harbouring the cfr gene, affecting five patients in a nephrology unit. Following the implementation of aggressive infection control measures, no further cases were detected beyond a two-week period.

Introduction

Glycopeptide-resistant enterococci (GRE) are important nosocomial pathogens, and patients with chronic kidney disease are a high-risk group for acquisition of these organisms [1]. The oxazolidinone antibiotic linezolid is a valuable therapeutic option for patients who develop infections caused by GRE. Linezolid resistance in enterococci is rare [2], [3], [4], but can arise during treatment and is most commonly associated with mutations in chromosomal genes encoding 23S ribosomal RNA, which are the target of oxazolidinones [2]. There are reports in the literature of cross-transmission and subsequent outbreaks of linezolid-resistant GRE with mutational resistance, but these are relatively rare [2], [5], [6]. Plasmid-mediated linezolid resistance has also been described internationally, mediated by the chloramphenicol–florfenicol resistance cfr gene [7]. The cfr gene was first detected in a bovine isolate of Staphylococcus sciuri in 2000, and there have been subsequent reports of cfr-positive isolates of both staphylococci and enterococci in humans [7], [8], [9]. In 2015, the optrA gene conferring transferable resistance to phenicols and oxaxolidinones was detected in isolates of E. faecium and E. faecalis in humans [10]. The emergence of linezolid resistance in hepatobiliary infections caused by E. faecium has been described in the UK with possible cross-transmission in this patient group [11].

This article describes an outbreak of colonization due to linezolid- and glycopeptide-resistant E. faecium harbouring the cfr gene in a UK nephrology unit. To the authors' knowledge, this is the first description of transmission of linezolid-resistant GRE harbouring the cfr gene, and this is the first time the gene has been detected in the UK.

Section snippets

Case definition

A probable case was any patient testing positive on a screening or clinical sample for glycopeptide- and linezolid-resistant enterococci. A confirmed case was one in which the cfr gene was subsequently detected in the positive patient sample. Colonization was defined as isolation of linezolid-resistant enterococci from clinical sites or from rectal screening samples without any signs or symptoms of active infection.

Outbreak setting

The outbreak took place in a regional nephrology unit within an acute hospital

Identification of linked patients

During this outbreak, five patients with pre-existing renal disease were found to be colonized with linezolid-resistant GRE. The index case was a 57-year-old male who was admitted directly to the medical unit after arrival in the UK from India. He had a history of chronic renal kidney disease and had a fistula in situ indicating preparation for renal replacement therapy in India. His English was poor and it was not possible to ascertain whether he had received prior therapy with linezolid.

Discussion

Linezolid resistance in enterococci is rare in the UK. The first isolates were reported in 2002 from three patients in geographically distinct parts of the country [17]. All three patients had received prior treatment with linezolid, and the isolates were found to have a G2576T mutation in the peptidyl transferase region of the 23S rRNA [17]. Linezolid-resistant GRE with this mutation have been reported elsewhere in patients who had not received prior therapy with the agent [6], and there have

Acknowledgements

The authors wish to thank the microbiology laboratory staff, Glasgow Royal Infirmary, colleagues at Health Protection Scotland and all members of the outbreak control team.

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