Tag Archives: CRE

What is a Superbug??

Image

You hear it every day in the popular press. It instills fear upon its very mention in a news release. But what exactly is a “Superbug?”

Let’s start with a search for “Superbug” on the internet. I did a google search and came up with a few definitions:

Maryn McKenna is a science writer and author of the popular book “Superbug.” She has written some fantastic blogs under the Wired Science blog Superbug. Her book focused on methicillin-resistant Staphylococcus aureus (MRSA), and her blogs have had a major emphasis on multidrug resistant (MDR) bacteria and the implications of antibiotic use on the rise of MDR bacteria. So, it would seem from Maryn’s standpoint that MDR bacteria with pathogenic potential represent a Superbug. That seems pretty logical to me.

Wikipedia states that “pathogens resistant to multiple antibiotics are considered multidrug resistant (MDR) or, more colloquially, superbugs.” States the same that McKenna implies.

Merriam-Webster dictionary defines Superbug as “a pathogenic microorganism and especially a bacterium that has developed resistance to the medications normally used against it.”

It looks like most sources agree on the definition of a Superbug. A pretty simple and straightforward one at that.

Now we get into shades of grey. What if we have trouble defining MDR and/or defining pathogen? For example, what if we find an MDR E. coli isolate on retail chicken such as that reported in the recent Consumer Reports investigation? The authors of this article spend a great deal of time discussing the implications of pathogen contamination of retail meat. But, if you look at the data, the prevalence of true pathogens of concern (such as Salmonella) is actually quite low, while E. coli isolation is more frequent. Still, they lump these together as “presence of bacteria on retail meat”. To make it clear, the classical diarrheagenic E. coli such as O157:H7 are not found on chicken. The biggest risk of E. coli in chicken is that some of these E. coli may have the potential to cause extraintestinal infections in humans, such as urinary tract infections (although this is still a controversial topic). However, the majority of E. coli from poultry do not seem to possess this potential. Survey studies such as the one conducted by Consumer Reports do not distinguish between whether or not an E. coli isolated from a chicken breast actually represents a possible human pathogen.

Let’s also look at the same report and their discussion of MDR. Their data (presented here) illustrates that MDR in pathogens of concern is again very low. Yet, they chose to lump all bacteria together in statements such as “Our test results found that 49.7 percent of our samples contained at least one multidrug-resistant bacterium.” This is again a shady area of the use of the word Superbug, since by definition it is a pathogen that has acquired MDR. Lumping all of these bacteria together as potential Superbugs is not appropriate. If the data were parsed to categorize Superbugs by pathogen type and MDR phenotype, then the data would be much less convincing. While it is convenient and sensational to lump them all together, it is an inappropriate use of the data.

Fortunately, the CDC is taking a lead on a better definition of Superbug. An article in CNN describes CDC’s proposal to categorize Superbugs by threat level. The levels are “urgent,” “serious,” and “concerning.” Those falling in the urgent category include MDR Clostridium difficile (C dif infections), carbapenem resistant Enterobacteriaceae (Klebsiella, E. coli, and Salmonella resistant to carbapenems), and Neisseria gonorrhoeae (causative agent of gonorrhoeae).

So, it seems that we are on the path to appropriately defining a Superbug, taking into account not only that a pathogen is MDR but also the ability of said pathogen to cause disease and hamper antibiotic treatment. A final issue is what policies should be taken to reduce the spread of these Superbugs. Here is probably the most important point – not all Superbugs become so in the same way. Some, such as CRE, pick up plasmids that make them MDR. Others acquire mutations that make them MDR over time. And they all spread differently, some through horizontal gene transfer, some through clonal dissemination, some using both. It is frustrating to see the media and activist groups misuse definitions to promote an agenda. Take, for example, the National Resources Defense Council, which starts this recent article with the following statement: “Feeding low levels of antibiotics to cows, pigs and chickens that aren’t even sick breeds “super bugs” — dangerous germs that are able to fight off antibiotics that spread to our communities and families.”

Now, I don’t disagree that we should judiciously use antibiotics in all settings, including animals. But as I have stated before, blanket statements such as the above one by NRDC are inappropriate. First, it implies that Superbugs as a whole are all impacted by use of subtherapeutic antibiotics in animal agriculture. Not true. Also, none of these reports ever reference articles demonstrating that subtherapeutic use of antibiotics in animals drives the emergence of Superbugs. I challenge you to do literature searches for articles demonstrating in a controlled experiment that this is the case. Believe me, I have tried, and there is nothing out there that convincingly demonstrates that this happens. This is why USDA/FDA have been lobbying for educated removal of certain drugs from animal production versus the mass removal of all antibiotics under a given claim. I think we really need to better consider the underlying science of policy making in this country, and support more science to make better decisions.

All this said, Superbugs are real. The name provokes a lot of unimaginable thoughts to people reading an article. We as humans are very good at sensationalizing and placing blame, less effective at promoting the right forms of change. Using a more concise definition of Superbug, let’s also promote the necessary science to address issues and solutions, rather than using public fear to promote changes in the absence of science.

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.