Gut Check: Carl Crawford, MD, on C Diff Infections

Dr Brian Lacy hosts Dr Carl Crawford of Weill Cornell to provide a comprehensive review of the causes, risks, and treatment of Clostridioides difficile infection.

Brian Lacy, MD, is a professor of medicine at Mayo Clinic-Florida in Jacksonville, Florida. Carl Crawford, MD, is an assistant professor of clinical medicine and program director of the Gastroenterology Fellowship program at Weill Cornell in New York City.

TRANSCRIPT

Dr Lacy:

Welcome to this Gastroenterology Learning Network podcast. My name is Brian Lacy. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida. I am absolutely delighted to be speaking today with Dr. Carl Crawford, assistant professor of clinical medicine and program director of the Gastroenterology Fellowship program at Weill Cornell in New York City. Our topic is one that routinely comes up in both the outpatient setting and the inpatient setting, C difficile colitis. Today we'll focus much of our discussion on recent advances in the field. Dr. Crawford, welcome. Clostridium difficile is an important topic for all health care providers. How common is C difficile colitis in the United States?

Dr Crawford:

How are you? I just wanted to start off by saying thank you for inviting me to speak with you today. It's a pleasure to be here. This is an area of academic interest that I've had for many years and I think it probably does not get as much airtime as many other diseases that we hear about. Now when I think about this particular infection that goes by a number of different names, whether it's Clostridium difficile or Clostridioides difficile or C diff, these infections take a huge toll on our health care system, patients, their families, and so many others that you would not think of as being directly in contact with that particular patient.

The burden of C diff in the United States is immense. There are close to 500,000 or half a million cases of C difficile that are new every single year. And this particular infection is unique because in some individuals, even after you're able to treat them, this infection can come back even after successful treatment. And if we have to think about the number of cases of these recurrences each year, it can total close to about 90,000 recurrences.

And this particular infection is known to be a diarrheal disease. So patients do get diarrhea, but there's a spectrum of disease where this diarrhea can become more and more severe to the point where some individuals require surgery to remove their colons and some people even pass away from this particular infection and they die in our hospitals. And if you had to think about that number, there are about 29,000 deaths per year from this infection alone within our health care system. And sometimes when we use big numbers like this, we forget that we're dealing with patients sometimes because they're just a number—29,000. But if you had to think about how many people could fit on a bus, that's about a busload of individuals, about 80 individuals dying every single day in our country from this infection alone.

Dr Lacy:

Wow, what a great way to put a perspective on it. And not surprisingly, because you're so knowledgeable about this, you kind of beat me to the punch and my segue was going to be kind of what's the impact of C difficile colitis on our health care system? And you already mentioned 500,000 cases per year, much more than I would've imagined. What about other impacts to our health care system?

Dr Crawford:

I think in order for our health care system to function, we have to be able to use a lot of our resources appropriately. So there is a huge economic impact from this disease in our hospital systems. So this particular infection probably adds on a price tag of close to $5 billion per year just to manage these infections and their recurrences. And of course there's other costs. These are costs to individuals that have to take time off of their jobs, individuals that have to take time off of their jobs to take care of the individual that's sick. And you can start to see how there are so many touch touchpoints to manage an individual that has a C difficile infection that it's more than just an economic price tag that this infection has. It's a social one as well.

Dr Lacy:

And I like that point, too, about sometimes it's not just the patient at home but family members and how it disrupts family life and cooking and shopping and cleaning the bathroom. It's also complicated and that really affects families and the patients. So Carl, what are risk factors for the development of C difficile colitis? Is it simply just that older patient with a recent course of antibiotic maybe for UTI or are there other risk factors that we should be on the lookout for?

Dr Crawford:

So that's an interesting question, but I can say that there's no one straight answer. However, if we have to think about taking a step back, why individuals get this particular infection, it's usually because they've been treated for something with antibiotics. So we consider antibiotics being a big risk factor. So sometimes individuals will need to be treated for a sinusitis, a pneumonia, a urinary tract infection, and they get appropriate antibiotics to treat that infection. However, there are so many useful and beneficial organisms that live in our gastrointestinal tract and in particular in our colon that sometimes there is collateral damage that makes us lose what's called colonization resistance. And because C difficile is very antibiotic resistant, it's usually the last organism standing in a depleted colonic flora. As a result that particular bacteria, C diff, can start to multiply and produce a toxin that causes this particular infection.

And it also lives as a spore, which means that it can always ball up and just go to sleep for several months and then wake up into an environment that still may be welcoming to it. So it's really the ability of an individual to maintain all of the good and healthy bacteria inside of their system that reduces that individual's risk to getting a C difficile infection.

So antibiotics will be the number 1 risk factor for a C difficile infection. However, there is data that show that individuals that are older in age, so if we were to use a cutoff of 65 and with each decade of life over that, the risk for acquiring C difficile goes up. And this is sometimes irrespective of antibiotic use. And the thought is that as we age, we develop a condition known as immunosenescence and that's where our body has a decreased ability to make antibodies or immune proteins that can help protect against this particular infection. So age would be a factor and we'll just say that cutoff is 65 years historically because we are seeing that the epidemiology may be changing and we're seeing individuals that don't fit this mold come in.

Now of course I mentioned immunosenescence, but we also have to think about the patients that we see in our hospital, in our offices all the time. And these are individuals that may have conditions where they have been immunosuppressed. So you can think about our patients that are on chemotherapy, that's an immunosuppressed state. We have patients that may have HIV or AIDS or are on other immunosuppressives for their rheumatoid arthritis or their autoimmune conditions. So there is another huge community of individuals that have a depressed immune system either because of their disease or because of the treatments that we use to help them with that particular disease.

Now of course, not everyone is at risk for getting a C difficile infection because you do need to have that organism present inside of your gastrointestinal tract. So if you think about exposure, exposure is a big risk. So where do these organisms actually live? They're quite ubiquitous. So they're everywhere in the environment, they're in the soil, they're in the park, they're here and there. About 3% of normal individuals that are walking around in the street are carrying a C difficile infection, but they don't have as much risk because that population is still very low. However, if one goes into a reservoir where there's a lot of this organism that's present, because there are a number of patients that are coming into these institutions with this particular infection and may be shedding spores—we can think about long-term health care facilities, so nursing homes, skilled nursing facilities, including hospitals. So the longer an individual is in a reservoir such as this, they increase the risk that C difficile will find itself inside of their system and just wait for the right conditions such as antibiotic use or stressful event in order to manifest itself. And one of the other risk factors that I would say is having had a prior episode of a C difficile infection is going to be a risk factor for another one in the future.

Dr Lacy:

That's such a great teaching point that certainly if you've had one episode, you are definitely more likely to have a second episode and we should be cautious then about using antibiotics inappropriately. So when should we suspect C difficile colitis? Should we just focus on that recently hospitalized patient with new watery diarrhea or there other hints that we should be focusing on when we see patients in clinic or the hospital?

Dr Crawford:

So C difficile infections are known to cause diarrhea. So some of our clinical suspicion will be an individual that we see, whether it's in the outpatient setting or the inpatient setting that's starting to have a change in their bowel habits. So they may start developing loose stools. Now when we think about the correct clinical scenario of an individual with this infection, we have to see if there's the presence of some of those risk factors that I mentioned as well as having an increase in their bowel frequency. Now sometimes individuals will have a change in their bowel habits for a variety of different reasons. They may change their diet, they may be exposed to medications, and so forth. So a lot of research companies and institutions and researchers got together and they decided that there's a minimum threshold of loose stools that we would expect to see in an individual that has C diff that would persist until it's treated.

And that threshold for us to start testing an individual to see if they have a C difficile infection in the right clinical scenario would be that person having 3 or more unformed bowel movements above their baseline in a 24-hour period for at least 2 consecutive days. And if you looked at your patient and you know that you did not prescribe them anything that could give them loose stools, whether it's magnesium, laxatives, tube feeds in the hospital, and all of a sudden they're developing loose stools after having had high-risk antibiotics, then I would say it is reasonable to test that particular individual to make sure that you are dealing with a C difficile infection and possibly not something else like salmonella, shigella, campylobacter, norovirus and so forth.

Dr Lacy:

Carl, thank you. So let's discuss the diagnosis of C diff now and the rules seem to keep changing. Obviously we're advancing medical knowledge and new things come up. What about GDH—glutamate dehydrogenase antigen? Is that still reliable? And what about PCR? Does that lead to too many false positives?

Dr Crawford:

Those are very, very tough questions and I think it's really because of how resources are allocated and how individuals will have access to these particular tests. Now, one of the things that we noticed when C difficile started to become a large burden on our health care system around 2000 was that it was very lethal. And I do remember seeing individuals come into the hospital and pass away within 48 hours of their diagnosis. So one of the useful tests was that glutamate dehydrogenase because it was present on all C difficile organisms. So if you wanted to make sure that your patient didn't have this potentially lethal and catastrophic infection, you would use this test because it was great as a screening test.

However, the downside of using this GDH is that it doesn't differentiate between all of the many different strains of this particular organism, mainly because not all C difficile organisms produce a toxin that lead to the disease. So this GDH test could identify an individual with C diff, but an individual that has a C diff that can't possibly cause their diarrhea. So it is a great sensitive test to make sure that you're capturing all of the patients you need, but it's not good enough to say that the presence of the organism is responsible for that diarrhea. It could have been that they have a strain that doesn't produce a toxin and they had bad Chinese food and now they're having diarrhea. And if you just relied on that GDH, you'd be making the wrong assumption.

Now, the PCR test or the nucleic acid amplification test, is still a very sensitive test, but it's designed to really pick out all of those organisms that are capable of producing a toxin. And there's different assays that look for the 2 major toxins that C diff makes— toxin A and toxin B—but it's really the toxin B that is responsible for a majority of the clinical cases that we see. So we don't have to worry so much about toxin A. And you'll see a lot of institutions just adopt the PCR that looks for toxin B.

Now, once again, this is just a test to see if the organism harbors the gene or the DNA. The issue is that you can have an organism that has this DNA, but the DNA is not being transcribed and a protein is not being made that will lead to this particular syndrome of diarrhea in that patient. So it is still a great screening test. It's a little bit more specific than in GDH, but it's highly sensitive and less specific. So once again, if you're in an area where C diff rates are really high, people are very, very sick, and you don't want to miss anyone, this is a great test.

Now that would just lead me to talk about one add-on to this test because if you had a good screening test, you should have a good specific test to make sure that that individual is actually manifesting a diarrheal symptom or syndrome related to the organism. And that's a toxin enzyme linked immunoassay or an EIA for short. And these tests actually look for the physical protein or the toxin that's responsible for the disease. And it's not recommended to be its own test mainly because you really have to get this toxin to the lab under specific conditions. But it is a great test when it comes back positive because you're absolutely sure that that individual has a C difficile infection.

Now of course, there are some instances where you may have a patient that, let's say, had a GDH that was positive. You sent them for a PCR test, that PCR test was positive, and then you come down to the final test, the toxin and the toxin is negative. And then you want to just make sure that this was not a false negative toxin. You want to make sure that maybe this test was not sent off too soon so that the test is not seeing low levels of this toxin and so forth. So sometimes a physician can make the clinical judgment or the decision that this individual had a sensitive test, all of the different clinical criteria of the loose stools and 24-hour periods, their exposures, all point to C difficile. Everything else has been ruled out. Even though this toxin is negative, it may be reasonable to consider a treatment. And that's really a case-by-case basis.

Dr Lacy:

Carl, that was wonderful and exactly why we're talking to you today, because this is not always straightforward. So thank you for highlighting those important facts. So let's move on now to treatment. And it's important to highlight that when we think about treatment, we need to consider if this is the first infection or as you mentioned before, that about 90,000 of those 500,000 patients have a recurrent infection. And so is there a specific treatment algorithm that you use for your patients with a first C diff infection?

Dr Crawford:

So the issue with antibiotics when we use them for C difficile infections are that they don't restore the colonization resistance or put back into that individual system all of the beneficial bacteria that they need to be resistant against C difficile infections. So my strategies for individuals that are coming in for their first recurrence is really to look at what they've been treated with the first time and to consider using something else because there's a saying, doing the same thing over and over again and expecting a different result is the definition of madness. And we've seen this over the years with C difficile infections using an antibiotic, the same one, the same duration over and over again. So the IDSA or the Infectious Disease Society of America, as well as the American College of Gastroenterology, came up with recommendations and I try to adhere to these recommendations because they're very thoughtful and it goes with using something different.

So for instance, there are 2 FDA-approved antibiotics for treatment of C difficile infections, just 2—that's vancomycin and fidaxomicin. And if someone was coming to me for their first recurrence, I would probably choose the antibiotic that has the least collateral damage or impact on the rest of the microbiome. I recognize that fidaxomicin would be the one that I think fits that bill. If an individual was treated with fidaxomicin the first time, and that's usually a standard dose of 200 milligrams twice a day for 4 days, I would give my patient the option to be treated again with fidaxomicin, but doing what's called an extended tap of using that antibiotic BID or twice a day for 5 days and then finishing off with 1 dose every other day for the next 20 days or 10 doses. And that's been shown to reduce the risk for a further recurrence.

Now alternatively, some individuals may not be able to afford this particular antibiotic, and in that case the default is vancomycin and vancomycin can also be dosed in either a tapered or a pulsed fashion. And that would mean giving an a standard dose of vancomycin followed by decreasing it by about 50% each week. So an individual would have the normal treatment of let's say 125 milligrams 4 times a day for 10 days. The following week they'd be on that dose BID for a week. The following week it'll be QD for a week the following week, every other day for a week. And then you can finish off with 1 dose of that vancomycin every 3 days for anywhere between 2 to 8 weeks depending on that clinical situation.

There are some other strategies that are not antibiotics. The IDSA and the ACG, they do recommend that one can try to boost the immune system by giving monoclonal antibodies.  That is reasonable as well for first recurrence in my patients that I find are immunosuppressed such as my IBD patients, whether they have Crohn's or ulcerative colitis. It's very useful even for those individuals that may be immunosuppressed for other reasons or they're expected to receive antibiotics shortly after antibiotic treatment course. But these are all different strategies for that first recurrence.

There is a newer strategy that has been moved to that first recurrence recommended treatment algorithm, but it's not in guidelines as yet. And we can probably talk about that in a little bit. But in terms of antibiotic strategies and things that are considered traditional, that's how I would approach first recurrences. Just do something that you didn't do the first time with the narrow spectrum antibiotic, probably having superiority over the old tried and true gold standard vancomycin.

Dr Lacy:

Wonderful, and we will circle back to that in a second. And then just to kind of focus on antibiotics and then maybe even close the door, in the past—30 years ago, 20 years ago—we're all taught to use metronidazole. That was kind of our go-to drug. Is it time to close the door on that now and just never use that?

Dr Crawford:

I think for, I don't want to say—never say never, right? So I don't want to totally throw away metronidazole because there are some situations where it's useful. So we know that it has worked in the past. We do know that it may not work as well for certain hypervirulent strains of C difficile. We do know that it's not as good at treating individuals that have moderate or severe or more severe complicated disease except in these particular circumstances that I can envision. One, you have a person that can't swallow, so you have fidaxomicin and vancomycin. They do require that you swallow them because they can't be administered intravenously. So if you have an individual that can't swallow, sometimes IV metronidazole has its role and individuals that are extremely ill in the hospital, sometimes they can't swallow, even if they can swallow, sometimes the inflammation is so severe that the gut does not move.  An oral antibiotic like have fidaxomicin or vancomycin will never get to the site of action that it needs to work. In the outpatient community, there are some circumstances where individuals may have allergies to something like fidaxomicin. An individual may not be able to afford vancomycin for whatever reason, and metronidazole is still affordable, probably to the underinsured or uninsured. So I feel that it is something that we should not forget about because it can be effective.

But in terms of treating patients the right way, and there was an editorial that basically was titled vancomycin for your mother, metronidazole for your mother-in-law. And that really shows that you can kind of use it, but there are better antibiotics than metronidazole that are out there that address the underlying pathophysiology disinfection. Use an antibiotic that can have the less impact on the microbiome and that is still have fidaxomicin. Vancomycin unfortunately does disturb the microbiome to a certain extent and can put patients slightly at increased risk for entering a cycle of vulnerability where they can develop relapses. Again, it's great at treating the organism, you can suppress C diff with both of those antibiotics, but we have to think about those recurrences at the end of the day, which is why my tried-and-true strategy is still fidaxomicin

Dr Lacy:

Wonderful. So let's take that patient who had documented C diff. You treat them and they note resolution of their symptoms, bowel habits back to normal, they feel great. How do we define treatment success? Is it just symptoms only or do we need to retest these patients?

Dr Crawford:

That is a question that I get asked a lot and it is worth saying this upfront: Do not retest to confirm clearance. If you have an individual that has had multiple bowel movements and you've been treating them with the appropriate antibiotic strategy, you would expect that they start turning the corner within the first 3 to 5 days of starting the antibiotics. This is what we see in clinical practice in the outpatient setting all of the time. In the hospital, sometimes individuals do need a slightly longer course of antibiotic therapy, but the goal is to really watch their bowel movements go back to baseline. Once an individual has had their stools go back to baseline, they're having formed stools, they're under the 3 unformed bowel movements within the 24-hour period for at least 2 consecutive days, they're probably in the clear. And you can just follow those individuals. You would not want to retest them.

And this goes back to the microbiology of this infection. It's really that the living vegetative forms are the forms that cause disease. Because they produce the toxin, the antibiotics take care of this, your body will flush them out. However, spores can sometimes remain and the spores are the dormant forms and they can sometimes test positive even though they're dormant on some of these assays. And what you do not want to do is test an individual for several months when they have documented improvement in their symptoms because you may pick up that particular spore that is not causing a problem at all. And because you use that very sensitive test and did not confirm with a toxin assay, most likely then you're stuck and your patient becomes panicked and you may become panicked because now you have what we would call a false positive, meaning that you've detected colonization and not infection.

Dr Lacy:

Wonderful—symptoms can be wonderful. Assess symptoms, don't retest is really the buzzword here. So thank you. So Carl, you so nicely covered treatment with antibiotics and that first recurrence. What about the role of bezlotoxumab? Where does that come into your treatment algorithm?

Dr Crawford:

So I use bezlotoxumab when it's available for my patients that I feel have been immune compromised for a variety of different reasons like I mentioned before— my inflammatory bowel disease patients who are receiving therapy, some of our bone marrow transplant patients who are having multiple recurrences of C difficile. I have found that in clinical practice, many have found that it was a little difficult to prescribe because it is a one-time IV infusion and ideally you have to time this infusion to the concurrent treatment of that patient for their active infection. The timing of giving this is not always easy. I think logistically it is difficult in practice, but it does have a particular patient population where it works really well.

And I think if I had to say in the back of my mind when I see a patient with C diff, who am I thinking about bezlotoxumab for? It's really high-risk groups. It's going to be my individuals that are possibly over the age of 65, an individual that's immune compromised for whatever reason, and individual who may have had a severe episode of C diff in the hospital and they're coming back with a recurrence because I would try to do everything in my power to prevent a recurrence that could possibly take their life. And of course, individuals that have had multiple recurrences of C diff in the past, I would say it's reasonable to consider using this as an adjunctive therapy and do something other than just using an antibiotic in that particular individual.

So it's a different strategy. And the beauty of this is that it doesn't alter the microbiome and individuals can still have some protection even in the setting of antibiotic use because this is really an antibody that binds to the free toxin and neutralizes that toxin so the toxin doesn't touch the colon cells and damage them. So I think in individuals that your audience may be taking care of, bezlotoxumab does have a role in the elderly, the immunocompromised, those that have had severe infections, and those that may have had virulent strains, because it's just another strategy that doesn't impact their colonization resistance.

Dr Lacy:

Wonderful. So you kind of have me naturally going into this next question when you were talking about other therapies. So no discussion on C diff would be complete without discussing the role of FMT, fecal microbiota transplant. Is this only appropriate for the most refractory or severe cases or should we consider it earlier? And is this really only for inpatients or outpatients?

Dr Crawford:

So the use of FMT or fecal microbiota transplants are very interesting because there was a long time ago a ‘ick’ factor that was associated with this. So just to describe briefly what FTS entail, it entails identifying a healthy human that has what we perceive as a ‘perfect’ microbiome, meaning that this individual is healthy, they have no clinical diseases, they have all of the correct populations of healthy bacteria inside of their colon that can resist against C diff. And the goal is really to restore in our patient that has recurrent C diff or even severe C diff, that colonization resistance in a heartbeat, in a snap. And honestly, when I started using this particular therapy for individuals, it worked like magic. It's one of the few things that I've seen in medicine that can take someone that's very ill and suffering and turn them around within a day or two.

And it's a therapy that's been used since 4^th-century China, and it really didn't come into the west until around 1958. And it was a surgeon who looked at his patients that had antibiotic-associated pseudomembranous colitis and decided to use this particular therapy, and it worked. And it fell out of favor until probably the 2000s, when we started seeing patients that were very, very sick and we weren't really using it for the very, very sick at that time, we were really using it for individuals that were coming back with these recurrences of C diff mainly because we knew that their colonization resistance was lost. So our societies basically have recognized—both the Infectious Disease Society of America and the American College of Gastroenterology—that this could be a therapy that is useful in individuals that have had multiple recurrences. And the FDA for quite some time had given us enforcement discretion to identify individuals who fit that criteria of multiple recurrences, at least 2 or more, to be appropriate candidates for this.

Now as an offshoot for compassionate use, we were using FMT in hospitals because the morbidity and mortality, or we can say the mortality, for an individual that needs a colectomy or their colon removed because the C diff is so severe, was about 80%. So in these individuals, you wanted to really throw the kitchen sink at them. You would give them vancomycin, IV metronidazole, you would give them vancomycin in a rectal enema suspension, you would have them in the ICU, you would cross your fingers, hope for the best, maybe use things that had no research behind it like IVIG, you would do everything because you didn't want your patient to leave this earth prematurely. And FMT became one of those options that we could use on top of everything else. And in many case reports and case series, we started to see that this was something that worked almost like magic, again, in these individuals.

And there are a number of case reports that have looked at the physiology of patients who are very, very ill and have seen that their pressor requirements had dropped after they were treated with just one dose of these products. The heart rates would start to normalize, the white counts would drop, patients would start to have normal stool, when they've been on all of the previously FDA-approved treatments for this particular infection. So it is now recognized that individuals can use FMT for multiple recurrences, but as an option when they are failing treatment in the hospital to have this done because it can be used to help salvage them.

Now there are products that are now on the market that do not have the label to use them in the hospital setting. However, as a practicing physician, I would still look at historically what has worked for my patients and I'm sure other gastroenterologists as well, that they would continue to use even some of these products that were not studied for this particular purpose just because of the biologic plausibility and the historical experience that we've all had.

So I think it'll work for pretty much everyone. And I think moving it down the algorithm to be used sooner so that our patients don't suffer multiple times over and over again is reasonable. But we also have to stop and think about, well, what are we really doing? Are we causing more harm? And that goes with not just FMT, but everything that we do. Whenever we're prescribing medications, we should stop and think is it safe for our patients? And we should always be re-evaluating why we're doing what we're doing. And I think there's no other product like FMT where there's so many optics and eyeballs on this particular field just to make sure that it is really safe for our patients going forward. And all of my patients that have this therapy for whatever reason, they go into a registry and the American Gastroenterology Association has a registry where we look at outcomes and we track patients 30 days, 6 months and every year for the next 10 years just to make sure that these patients are safe. And I don't know any other therapy where we actually follow our patients that closely. So yes, I think it should be moved in sooner, but I think it is not something that you should just fire and forget.

Dr Lacy:

Wonderful. And Carl, as we wind down here, last 2 bullet questions. Probiotics—something we should use or recommend? And what about fecal microbiotia spore therapy (Vowst) something we should use or recommend?

Dr Crawford:

So I'm going to have a quick answer for the probiotics and the probiotic question would be no, we don't use probiotics for either the prevention of C diff or to prevent its recurrences, mainly because the key to preventing C difficile or not even getting it is biodiversity. You're probably better off eating a healthy diet that has prebiotics or healthy fibers from fruits and vegetables to help restore all of those good bacteria inside of the gastrointestinal tract that probiotics really are not ideal. And there have been mouse studies that have looked at, well, what is the recovery of the microbiome after antibiotic exposure? And mice that receive probiotics have less recovery of their microbiome than mice that were treated with antibiotics and were allowed to have their microbiomes recover spontaneously. And because we need as much spontaneous recovery as we can imagine, you're better off not using probiotics. So we recommend against the use of probiotics.

Now, when we think about the landscape of FMT, the FDA recognizes that we're using FMT as a drug because we're using it to mitigate or treat a specific disease. And they've reclassified products that have been studied rigorously to be used for this particular reason, to prevent recurrences of C difficile infection. And that new class of medications is called Live Bacterial Therapeutic Products or LBPs. There is a product that has been studied, RBX2660 is the name of the drug that was studied, that's on the market and was FDA approved about a year or so ago for the prevention of C diff recurrences. Now that uses donor stool that's humanly sourced to do the same thing that we've done traditionally. However, that particular LBP is a little bit different because it has been selected to contain a high number of a specific set of classes of bacteria that help prevent recurrences.  And that's bacteroidetes and clostridia. So this particular company can provide stool that is set up for success and restoring colonization resistance for those who are receiving it.

Now, some individuals are concerned about what's in FMT products because there's so many different microorganisms that it's not just bacteria— it's viruses, it's phage, it's protozoa. Now do we really need all of those things? And there's a company that actually decided to look at ecospores [microbiota spores], just look at firmicutes, which is a particular phyla made up of gram-positive organisms that are spore formers. And they took this material from humans and they basically, alcohol washed out everything that was alive. They were able to get rid of living bacteria. All the vegetative forms, yeast, fungi, protozoa, viruses all eliminated and they spun down and they just collected spores. And they found that when they were able to give these spores back to individuals that had one or more recurrences of C difficile, it worked very similarly to what we would see with historical FMT.

Now in the trial, they didn't compare it to FMT, they really compared it to standard of care. So all of the individuals that had standard of care, they would relapse. But a lot of the individuals that received these ecospore pills actually were able to maintain their clinical cures after the standard of care antibiotics. So it does work in some of the plausibility of just using this particular niche of bacteria is that they do help restore some of the metabolic functions that are helpful in suppressing C difficile outgrowth. These particular bacteria are notable because they convert primary bile acids in the GI tract into secondary bile acids. And we've studied over the last several years that the secondary bile acids keep C diff from spoilating and germinating. So you're able to suppress C diff when these particular bacteria are present. So it works just like our historical FMTs, but there is a convenience associated with this and that is that this can be shipped to a patient's home and they can do this themselves, and it obviates the need for them to have to prepare for colonoscopy to have this instilled in the rectum in the office. They can do it from the comfort of their homes.

Dr Lacy:

Wonderful. Carl, this has just been a wonderful conversation. I can't thank you enough. Any last thoughts for our listeners?

Dr Crawford:

I think for all of our patients and caregivers that are out there, it is been about, I would say close to 20 years where we were really dealing with an infection that was like this. And it took us a long time to get to where we are, where we can test this particular infection appropriately, treat an individuals to get their symptoms under control, and now we have products that are on the market that can actually help break the cycle of recurrences of this particular infection. So from start to finish, it took us 20 years, but everyone's been working hard and we actually have something that can help a majority of our patients. And I'm hopeful that that number of 500,000 of new cases per year, the 90,000 recurrences, even the 30,000 deaths will all continue to drop each and every year. I think it's very important that you get this kind of message out to all of the health care providers to patients so that they get treated appropriately.

Dr Lacy:

Okay, Carl, again, thank you so very much for lending your amazing expertise on this important topic to our listeners on Apple, Spotify, and other streaming networks. I'm Brian Lacey, a professor of medicine at the Mayo Clinic in Jacksonville, Florida, and you have been listening to Gut Check, a podcast from the Gastroenterology Learning Network. Our guest today was Dr. Carl Crawford from the Weill Cornell Medicine in New York City. I hope you found this just as enjoyable as I did, and I look forward to having you join me again for future gut check podcasts. Stay well.