CRE: latest catch phrase in infectious disease

You have probably heard in the news about CRE, or carbapenem resistant Enterobacteriaceae. The MN Department of Health has a very nice page on CRE here. CRE has certainly gotten a lot of hype about being the next major “superbug” – and this is with good reason. But I wonder if the media going to the well one too many times for the “superbug” catchphrase is going to hurt us all in the long run? Is CRE really a superbug? It is important to note that CRE actually represent any Enterobacteriaceae that are resistant to carbapenems. This can encompass a wide variety of bacteria causing different diseases. The major player is Klebsiella pneumoniae, which is most commonly associated with urinary tract infection and resulting sepsis. This type of infection, if untreatable with antibiotics, can certainly be deadly. This is the worst case scenario, and there are a range of infections in between that can involve CRE and may or may not require antibiotic treatment. I think there are some important points to consider when discussing CRE.

CREs are mostly created through the conjugative transfer of plasmids that encode a carbapenemase. These can include KPC, NDM, and VIM. The latter two have emerged in the US only recently, but KPC in K. pneumoniae has been around for a while. The dangers of these genes being carried on plasmids is that they can move between bacteria via bacterial conjugation, and these plasmids can carry resistance to additional antibiotics. What is not well understood at this point is the extent to which conjugation occurs and precisely where these plasmids tend to spread. Plasmids encoding KPC, NDM, and VIM are diverse and confer different arrays of resistance phenotypes. It is clear that selective pressures are driving the integration of these genes into a variety of plasmid types, but it is less clear why certain plasmid types (such as IncA/C) are able to carry these genes and so many other resistance genes at the same time, with little cost to the bacterial host. One thing is clear – our labeling of these plasmids as “promiscuous” (like I have done many times) needs to be done with caution. If plasmids such as IncA/C were as promiscuous as I originally thought they were, they would have easily swept E. coli and Salmonella populations by now and we would be experiencing a pandemic of MDR E. coli and Salmonella carrying IncA/C plasmids (and CRE bacteria). This is not the case and probably will not ever be the case. There is something that limits the dissemination of these plasmids among E. coli and Salmonella. Could it be a quorum sensing mechanism that limits the conjugation of this plasmid? Maybe. But my main point is that CRE is certainly concerning. It is a fascinating research topic. However, I am hesitant to call CRE a superbug because my view of a superbug is a potential global killer. Let’s hope that CRE does not reach that status.

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