Rapid Molecular Diagnostics for C diff and Sepsis

In a presentation at the 6^th International C diff Awareness Conference and Health EXPO in Philadelphia, Pennsylvania, Maureen Spencer, RN, M.Ed., director, clinical implementation, Accelerate Diagnostics, discussed how rapid molecular diagnostics are changing the treatment timeline for sepsis and Clostridium difficile (C diff).

In an exclusive interview with Contagion®, Spencer discussed the link between sepsis and C diff and how critical it is to develop rapid technologies that will reduce side effects and mortality that accompany delayed optimal therapy.

Contagion®: What is the connection between sepsis and C diff?

The connection between sepsis and C diff goes back to what I said about the side effects of antibiotics. There were 2 meta-analyses published back in 2013 and 1 of them found that there's a 7-fold increased risk if you've been on antibiotics of getting C diff and then another study found the same thing tripled the risk by just being exposed to an antibiotic. And so, there are certain antibiotics that increase the risk of C diff. The first one’s clindamycin followed by a group of antibiotics called fluoroquinolones, and then there's another set of antibiotics called cephalosporin; those are our high-risk antibiotics that are associated with the development of C diff.

The thing I'm most excited about is rapid technology that can identify the bacteria in the blood faster and so we're very blessed right now that we have many companies that can do that. We have some that are called polymerase chain reaction (PCR) that within an hour you could identify an organism in the blood. We also have genotypic types of techniques such as a product called the MALDI (MALD-TOF) which can give you a result in about an hour to an hour-and-a-half, and then there's the Accelerate Pheno [system], which also gives you a result based on a phenotype rather than the gene of the organism, [which also gives results in] 90 minutes; however, what's unique about that technology is it will go on within another 5 hours to give you the sensitivity. So, the physicians need to know what to treat the patient with, and typically an antibiotic sensitivity test (AST) takes anywhere from 2 to 4 days and this is done in 7 hours.

By first identifying the organism very quickly and then being able to know what antibiotics that it’s sensitive to and what they can treat them with, will help drive that therapy to get them treated on optimal therapy and deescalate get them off those antibiotics that they don't need.

The challenge right now for physicians is they will leave them on empiric therapy, even if they know the identification of the organism, they’re sometimes not quite sure so they'll wait the 2 or 4 days and then that's where you start to see the C diff or other multiple drug-resistant organism (MDROs) growing. We have to think that antibiotics can wipe out the microbiome and the whole body is completely now a landscape for anything that wants to come in.

It doesn't have the normal flora that would typically keep it in balance, and so C diff will take the opportunity to overgrow where there's no other microbiome that should be there. And there are other species that in the presence of the antibiotic will start to develop resistance and start to grow in the presence of that antibiotic because they figured out how to get resistant to it.

Contagion®: How important is timely treatment for sepsis and C diff?

There have been many studies done, 1 in particular, called the Kumar study showed [that] once the patients start to get hypotensive and look like they're going into shock, for every hour you delay the appropriate optimal therapy there is 7.6% decrease in survival. And so, when you look at the data at 36 hours it's only 5% survival, so that's one of the challenges is that our delayed laboratory test are making us wait those days to be able to give them optimal therapy.

There was a study that was just published in June looking at all the rapid ASTs that were coming on the market and so there's tons of research being done in that field and research and development to look at how can we get faster ASTs. The only one on the market at the moment for blood cultures is the Accelerate Pheno, so Accelerate Diagnostics has a rapid 7-hour ID and AST test that's available now and approved by the FDA.

There's another issue that comes up with sepsis is called post-sepsis syndrome and the problem there is that patients are often in the intensive care unit for days, weeks, or months depending on the criticality of the situation. [On average,] 38 people per day have an amputation due to sepsis and they're going to be in the ICU much longer. Because of that many of them have insomnia they can’t get to sleep or stay asleep, they have aches and pains and their muscles and joints, many of them have decreased mental functioning, they have nightmares and terrorism panic attacks, and there's a 42% increased risk of them committing suicide if they have had sepsis. We are just starting to learn as we study sepsis, some of those other side effects and what happens to the patient after they leave the hospital and what their quality of life is following a septic episode.