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GRE (VRE) is it so concerning?

16/12/2013

 
Picture
Firstly let’s clarify some 3 letter
acronyms. VRE is commonly used and stands for Vancomycin Resistant Enterococcus but Microbiologists prefer to use the term GRE (Glycopeptide Resistant Enterococcus) because GRE is a class resistance, resistance is to the entire  Glycopeptide class (which is both Vancomycin and Teicoplanin). This is similar to MRSA which is resistant to all Beta-lactams not just Meticillin, technically MRSA should really be known as Beta-lactam Resistant Staphylococcus aureus BLRSA! Using the term GRE acts as a prompt not to use any Glycopeptides e.g. Teicoplanin, as an alternative treatment.

Many healthcare staff believe that Microbiologists are concerned by GRE as it is very difficult to treat, requires the latest antibiotic treatments and patients must therefore be isolated from an infection control perspective. After all this is a new superbug...Right?!?

Not really! It is true, that GRE infections are difficult to treat, but Enterococci are naturally equipped with many methods to resist routinely used antibiotics (e.g. no target site for
certain Beta-lactams, ability to bypass folic acid pathways or have mutations of the antibiotics active site) making them inherently more resistant to antibiotics than many other bacteria. And yes, there are limited antibiotics available to treat GRE such as Linezolid or Tigecycline (both only
bacteriostatic) or Daptomycin (potentially more toxic) but remember Enterococci only very rarely cause significant infections.  So why the hype and why are Microbiologists so concerned?

The real reason why Microbiologists are worried about GRE is in the way it has become resistant to the Glycopeptide antibiotics. GRE has acquired a new gene called VanA, which changed the structure of the Enterococcus cell wall therefore making it resistant. This gene can be passed onto other bacteria making them resistant too.

So if the GRE gene can potentially be transferred from GRE consider the consequences if it transfers to more pathogenic bacteria such as Staphylococcus aureus or Streptococcus
pneumoniae
, or consider how dangerous it would be if the GRE gene entered MRSA, resulting in the creation of Glycopeptide Resistant Staphylococcus aureus (GRSA). 

GRSA, unlike GRE, would cause many infections, some of which would be life-threatening. The presence of the GRE
gene in GRSA would mean that first line MRSA antibiotics (Vancomycin and Teicoplanin) could not be used resulting in an increased number of patient deaths. GRSA is not fictitious or theory it has already been reported (in the USA where the outcomes suggest a 63% mortality if resistant to Vancomycin versus 12% if not resistant). This transferability of the VanA gene is why Microbiologists worry about GRE. 

Another confusing point can be best explained by an example. Recently I advised a junior doctor to remove his patient with GRE from the side-room in order to isolate another patient. He looked perplex and asked, why do Microbiologists get so concerned (read grumpy) about isolating patients with GRE and then at other times seem less concerned!? I laughed and asked what the lab report said. He read Enterococcus casseliflavus. I smile again; of course he is right Microbiologists may “appear” to change our minds over the significance of GRE but the reason is not our mood swings; it is about genetics, the bacteria’s, not Microbiologists!! I’ll explain…

Fortunately, the GRE gene is only transferable from certain species of GRE, in particular Glycopeptide Resistant Enterococcus faecium  and Enterococcus faecalis. In these species the GRE gene is on a transposon, a piece of genetic material that can readily transfer between bacteria of the same species and sometimes bacteria of different species. Patients with these are very concerning and definitely need isolating as they have a high risk for transferring the GRE
gene to other bacteria e.g. MRSA.

However, there are some species of GRE (Enterococcus casseliflavus and Enterococcus gallinarum) in which the GRE gene is part of the chromosome and not on a transposon. This form of GRE gene cannot be transferred to other bacteria. Seeing these bacteria on a lab report is of less concern as they rarely cause serious infections and cannot transfer their resistance. Microbiologists are less concerned about these types of GRE as they are not a high risk to transfer the GRE gene to other bacteria.

What does this mean in a nutshell...
ISOLATE ALL SUSPECTED GRE...You may feel confident to look at the lab report and identify if the species transfers the GRE gene via a transposon, in order to re-evaluate the need for isolation. However, in practise most healthcare staff don’t have immediate access to the result or more likely get confused by which species transfers the GRE gene via a transposon. Therefore most hospital policies isolate all GRE patients. Microbiologists may remove a GRE patient from isolation when a higher isolation priority patient requires the side-room; they advise this based on the laboratory identification, their knowledge of GRE species and mechanisms of resistance of the genetics.

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    Blog Author:

    David Garner
    Consultant Microbiologist
    Surrey, UK

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