KPC Casanova carbapenemase

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The risk of interspecies transmission of carbapenemase genes is a real concern. We can barely get our heads around many different types of carbapenemase in a whole host of Gram-negative bacteria (compare the relative simplicity of methicillin resistance in S. aureus: a single gene, in a single species). Throw in interspecies horizontal transmission of carbapenemases and things get really tricky! Do we implement different control strategies to try to interrupt the transmission of carbapenemases (in contrast to the organisms themselves)? Could you have a multispecies outbreak of a carbapenemase on your hands and not even realise it?

A NEJM study reports a case of a man with multiple hospital exposures (and I mean multiple – 21 admissions over 5 years!), and exposure to pretty much all key classes of antibiotics. 14 KPC-producing CPE were identified over this period, in three separate species. 9 of the 14 KPC-producing CPE were sequenced, yielding strong evidence of intra- and inter-species spread of KPC by both transposons and plasmids. However, since the sequence of carbapenemases is extremely well conserved, possible horizontal transmission needs to be inferred by the sequences either side of the carbapenemase. Whilst there is a slim possibility that this could be explained by multiple, independent transmission events, horizontal transmission of KPC seems the most likely explanation.

A few reflections on these findings:

  • It is a complicated story. It took me a few reads to get my head around the detail of this short, well-written article. It will be a challenge to communicate this to junior staff or non-clinical hospital administrators.
  • I could imagine a scenario where is it really not clear whether a hospital does in fact have an outbreak or not! Would you call an increase in the number of reports of the same carbapenemase in different species an outbreak in the same way that you would if it was the same carbapenemase in the same species?
  • What are the infection control implications here? We don’t have the resource to WGS sequence every CPE that we see. And even if we did, we don’t have the bioinformatics capacity (described as ‘artisan genomics’ by somebody on Twitter) to make sense of it. And even if we did, it wouldn’t come back in a useful timeframe to actually make a difference on a ward level. We have taken the pragmatic view to focus on potential same-carbapenemase-same-organisms transmission events from an infection control viewpoint, whilst recognising the possibility / risk of horizontal gene transfer.
  • Microbiology is considerably more polyclonal than we may assume from looking at a ‘pure culture’ on an agar plate. Firstly, a ‘pure culture’ is far from monoclonal. During my PhD (on MRSA molecular epi), I was always a little disturbed by the need to pick five colonies from an agar plate in order to extract DNA for analysis because of the concern that you may not capture the full degree of molecular diversity from a single colony. Secondly, bacteria live in a very polyclonal world, and odd things start to happen even when you co-culture a couple of different organisms (indeed, this is the basis of quite a few lab experiments). We are only scratching the surface of understanding what is going on in diverse and dynamic polyclonal environments.
  • NEJM have unhelpfully permitted ANOTHER acronym related to CPE: KPC-producing Enterobacteriaceae (KPE). This is an especially unhelpful one: would the proposal to have a related acronym for each carbapenemase class (OPE, VPE, IPE, NPE, GPE and on and on)?! Let’s just still to CPE and spell out the rest shall we?

This paper adds weight to the concern that horizontal transmission of carbapenemases is a live risk, but I can’t think of much that we can do about this over and above our usual management of CPE. Answers on a postcard please!

Image: Wikipedia.

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