Restoring Balance with Advanced Fecal Microbiota Transplantation in C difficile Infections - Episode 1

Restoring Balance with Advanced Fecal Microbiota Transplantation in C. difficile Infections

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Dr Paul Feuerstadt joins Dr David Hudesmand and Dr Jordan Axelrad in a discussion about treatment approaches for C difficile infections, and the latest advances in treating recurrent infections with fecal microbiota transplantation.

David Hudesman, MD: Hello, and thank you for joining this MEDcast series titled “Restoring Balance with Advanced Fecal Microbiota Transplantation in C Difficile (Clostridioides Difficile) Infections.” I am David Hudesman, MD, codirector at the Inflammatory Bowel Disease Center at NYU Langone Health in New York, New York.

Jordan Axelrad, MD, MPH: I am Jordan Axelrad, MD, MPH, director of clinical and translational research at the Inflammatory Bowel Disease Center at NYU Langone Health in New York, New York.

David Hudesman, MD: In this program, we’ll explore the latest advances in treating recurrent C difficile infections with fecal microbiota transplantation [FMT] and examine the clinical evidence supporting its use. To discuss more of this, we are joined by Paul Feuerstadt, MD, FACG, AGAF, assistant clinical professor of medicine at Yale University School of Medicine in New Haven, Connecticut. Paul, tell us a little about what type of patients or people are at increased risk of C difficile infection.

Paul Feuerstadt, MD, FACG, AGAF: There is a wide array of patients that are at risk for C difficile infection, which is why so many patients get it. About a half a million people will get diagnosed with C difficile in the United States every year. The risk factors for C difficile fall under 3 categories: demographics, medication exposure, and environment.

Demographically, seniors and women are at increased risk for C difficile infection, as well as those living with chronic kidney disease, HIV, diabetes, or inflammatory bowel disease [IBD]. Patients that have had C difficile in the past are also at significantly increased risk.

As for medication exposures, the classic association is with antimicrobials. The most common antimicrobials associated with C difficile are amoxicillin, ampicillin, erythromycin, fluoroquinolones, cephalosporins, and piperacillin and tazobactam. These antimicrobials have an impact on our colonic microbiota, which creates an environment that’s much more welcoming for C difficile to proliferate. In my practice, patients often come in on a PPI [proton pump inhibitor] or histamine blocker to treat diseases such as GERD [gastroesophageal reflux disease]. H2 [histamine type-2] blockers and PPIs are also risk factors for C difficile infection.

The third group is environment. Any individual that lives in a skilled nursing facility or spends significant amounts of time in the hospital are at greatest risk. They probably fulfill the other risk factors I listed in terms of demographics and medication exposures, and they are also surrounded by other patients that might have C difficile. It is a confluence of challenges.

David Hudesman, MD: You illustrated nicely how prevalent this disease really is. What is the recurrence rate of a patient who has previously recovered from C difficile? Does 1 recurrence increase the risk of further recurrences?

Paul Feuerstadt, MD, FACG, AGAF: That is a really important question. Recurrences are a major Achilles heel with C difficile infection.

An estimated 35% of properly treated patients will recur within 8-12 weeks. Of those recurring infections, 45% will recur a third time, and up to 60% will recur after that. Patients get caught in this vicious cycle of recurrence after recurrence after recurrence. That causes a huge burden on our health care system. Recurrences predict an increased risk of sepsis and colectomy, as well as increased risk of C difficile-related mortality. It is a significant financial burden. There is a burden on the patients beyond abdominal pain and diarrhea associated with C difficile. They may experience a health care-related quality of life impact, anxiety, or PTSD [post-traumatic stress disorder]. These patients live in fear that they are going to get C difficile again because the rates are so high for recurrence.

David Hudesman, MD:Could you tell us about how the gut microbiota is linked to C difficile?

Paul Feuerstadt, MD, FACG, AGAF: The microbiota is a complicated space. It is estimated there are a hundred trillion different microorganisms in a healthy colon. It is made up of bacteria, archea, fungi, yeast, and viruses. In the medical field, we gravitate towards the things that we have defined the best and understand the most. We understand the bacterial phyla within the colon the most. The most common bacterial phyla in a healthy colon are the Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, Verrucomicrobia, and Fusobacteria. I believe that’s what makes our society great is our diversity. Different people from different backgrounds approach things in a different way to solve problems efficiently. It is the same thing in the microbiota. The more diverse the microbiota is, the healthier the microbiota is because it can approach problems in a more sophisticated, efficient way.

The composition of the microbiota is what is most eloquently defined, but what this bacteria is doing is more important. C difficile is a really interesting bacteria because C difficile has 2 phases: the spore phase and the vegetative phase. The spore phase is really resistant. It’s possible that C difficile is sitting on a surface right in front of you in its spore phase, because the spore phase can last on that surface up to 8 months and remain viable. It’s the spore phase that gets transferred from person to person. Healthy microbiota eradicates the spore phase. Antimicrobials have minimal to no impact on C difficile spores, instead impacting the vegetative phase. The vegetative phase of infection releases toxins and causes symptoms, such as abdominal pain, diarrhea, nausea, fevers, and sweats. Antimicrobials control the vegetative phase, which is why when patients are on antimicrobials, they respond, their symptoms go down. The spore phase [of] C difficile then stays in a patient’s system, and it’s up to a healthy, diverse microbiota to give that spore phase the knockout punch.

David Hudesman, MD: Over time, our diagnostic approach to C difficile has changed. Walk us through your approach and tell us how the IDSA [Infectious Diseases Society of America] and ACG [American College of Gastroenterology] guidelines have changed. What should providers be doing when they evaluate a patient with diarrhea?

Paul Feuerstadt, MD, FACG, AGAF: The incidence of health care-associated infections is decreasing because of better infection control and antimicrobial stewardship. Essential to understanding a patient with C difficile is understanding the diagnostic tools. There are 3 commercially available tests: the enzyme-linked immunosorbent assay [EIA], the GDH [glutamate dehydrogenase] assay, or the PCR [polymerase chain reaction]/NAAT nucleic acid amplification testing.

Let’s start with the EIA, or enzyme-linked immunoassay. In the distant past, doctors would have to send off 3 consecutive bowel movements to diagnose C difficile, because the sensitivity of the EIA at that time with 1 test was completely insufficient. In about 2008-2009, the sensitivity improved, but it wasn’t great. The enzyme-linked immunoassay is the only test that we have commercially available that detects a true diagnosis of the C difficile toxin itself. We don’t necessarily care if C difficile is in a patient system, we care whether it’s in the patient system and producing toxin. But the EIA still has an unacceptably low sensitivity. If it’s positive, you can confidently say that the patient has active C difficile. But if it’s negative, you can’t say that they don’t have C difficile.

We do secondary tests to boost the overall accuracy. One of those secondary tests is the GDH assay. This assesses for an enzyme that is broadly released by Clostridium species, but not necessarily toxigenic C difficile. A positive test means you possibly have C difficile, and a negative test means it is incredibly unlikely that you have C difficile. It has a high negative predictive value. If you put the EIA and GDH together, you get a pretty good test. If they’re both positive, you’re positive. If they’re both negative, you’re negative.

However, we frequently will get discordant results. We adjudicate those discordant results with a test called the PCR assay. The PCR assay is an assay that detects the genes that code for the toxin, not the toxin itself. So it detects the organism, but not whether the organism is actively releasing toxin. Well, when you’re adjudicating discordant results, perfectly acceptable test. If you’re positive, you say the patient’s positive. If they’re negative, you can say that the patient is negative.

But there’s been a significant shift in our society. A study published in the New England Journal of Medicine in 2020 looked at the frequency of testing in the United States in 2011 versus 2017. In 2011, the predominant assay that was used was the enzyme-linked immunoassay. The estimate for the number of cases in the United States was 476,400. That was based on the frequency of EIAs being true positives.

However, in 2017, the frequency of positive tests was essentially the same, but the PCR assays were being used as a single test about 80% of the time. They adjusted the frequency of diagnosis of C difficile down to 365,200 to account for colonizers. Fifteen percent of all health care providers, of all individuals that spend significant amounts of time in the hospital have C difficile within their system without an active infection. PCR assays on their own will over-diagnose. Following IDSA/AHA guidelines and clinically contextualizing those patients will fix that. The patient should be having at least 3 liquid bowel movements in a 24-hour period. The stool should take the shape of the specimen collection container.

David Hudesman, MD: We see a lot of inflammatory bowel disease patients in the hospital system. Be very careful on who you’re testing.

Jordan Axelrad, MD, MPH: Know what tests your institution has available and know how to use them.

David Hudesman, MD: Exactly. If a patient tests positive, is your first-line agent metronidazole, vancomycin [Vancocin], or fidaxomicin [Dificid]? How do you make that decision?

Paul Feuerstadt, MD, FACG, AGAF: The guidelines say that fidaxomicin is superior to vancomycin. Fidaxomicin has a narrow spectrum. What that means is that when you treat C difficile, it is targeting just C difficile, having a minimal effect on the surrounding microbiota. Vancomycin treats C difficile, but also alters that surrounding microbiota, creating an environment that results in higher recurrence rates. If they are positive, the tendency is to want to treat. If you treat with vancomycin, you can alter the microbiota in a way that causes C difficile to reactivate because you’re weakening the colonization resistance. True diagnosis is key. Fidaxomicin is preferred.

In my clinical practice, I wait if patients have 2 or more risk factors for recurrence. In that group, considering the financial elements, I use fidaxomicin. An acceptable alternative is vancomycin 125 mg 4 times daily. Metronidazole has largely been phased out. There’s data from 2005-2007 showing that metronidazole was inferior to vancomycin. That gap has widened even more significantly over the last 15-17 years. In the guidelines, they recommend metronidazole if neither fidaxomicin nor vancomycin are available, if the white cell count is less than 15,000 and the creatinine is less than 1.5 mg per deciliter.

A lot of these patients do in fact recur. The first recurrence, according to the guidelines, should be treated again preferentially with fidaxomicin 200 mg, twice daily, for 10 days, or fidaxomicin 200 mg twice daily for 5 days, bought by 1 tablet every other day, day 7-25. An acceptable alternative is vancomycin in a taper and pulse fashion more than 6 weeks. And then finally, if somebody failed metronidazole, initially, we could consider giving a 10-day course of vancomycin. In clinical practice, I use fidaxomicin for first regards. If they fail fidaxomicin, I use vancomycin taper pulse for that first recurrence. This is also where a product called bezlotoxumab was added. Bezlotoxumab [Zinplava] is a fully humanized monoclonal antibody designed to bind toxin B in a specific way. It is an infusion given during the standard of care antimicrobial that helps prevent recurrence.

Jordan Axelrad, MD, MPH: Let’s talk about the duration of standard care antibiotics. How much benefit does the bezlotoxumab give patients as far as reduction and recurrence?

Paul Feuerstadt, MD, FACG, AGAF: For an IBD population, I would tend to use a more prolonged cause of vancomycin. I don’t necessarily go full 20 days. I usually go about 14 days as opposed to the 10 as recommended in the IDSA/SHEA [Society for Healthcare Epidemiology of America] guidelines and the ACG guidelines. I am more aggressive in patients that have higher risks for future recurrence, such as IBD.

Bezlotoxumab has fascinating data associated with it. From the MODIFY I [NCT01241552], MODIFY II [NCT01513239] trials, the number needed to treat to reduce 1 recurrence overall was 10. When they looked at … risk factors for recurrence, such as being over 65 years old, having any form of immune compromise, having history of C difficile within the previous 6 months, the presence of the NAP1/B1/O27. or hypervirulent strain. or severe infection defined by a white cell count greater than 15,000 and or creatinine greater than 1.5 milligrams for deciliter; these patients benefited specifically the age over 65, the number needed to treat was 6. It almost cut the number to treat in half. The bulk of the patients that we see with C difficile in general are those over 65, so that is a sweet spot for bezlotoxumab.

A subgroup analysis looked at those 5 risk factors and it found that if a patient had just 1 risk factor for recurrence, the recurrence rates were about 31.3% with placebo versus 17.1% bezlotoxumab. In clinical practice we usually use at least 2 risk factors for recurrence. IBD, a great population to certainly consider with regards to this. There is very heterogeneous data that show a significant benefit, but in my clinical practice I will use this more aggressively in an IBD population. The 1 population we have to be careful with bezlotoxumab with is in patients with CHF [congestive heart failure]. Within the MODIFY I and MODIFY II trials, there was a slight increased risk of CHF exacerbation.

Jordan Axelrad, MD, MPH: Could you give us an overview of what we have now? When are you implementing next-stage microbial therapeutics for recurrent C difficile?

Paul Feuerstadt, MD, FACG, AGAF: We’ve gone from the rudimentary fecal transplant world to a more sophisticated approach. Fecal transplant works because we know that there’s deficiencies of bacteroidetes and firmicutes in patients that have C difficile infection. We know that those bacteroidetes and firmicutes create an environment in the colon that helps eradicate that spore phase. Unfortunately, our body’s ability to naturally regrow the bacteroidetes and firmicutes does not work well, which is why recurrences are so high. The theory with fecal transplant to replace what is deficient, thus reducing rates of recurrence. This has worked wonderfully over the last 10 years in widespread practice.

We were really learning along the way what we were doing. It seemed to work, and [when] we reinforced that it seemed to work. We had a bunch of open label studies. We had a couple of randomized controlled trials. There are a couple safety signals, but fecal transplant was overall safe. But there was a lot of heterogeneity of the trials. What the next phase looks like are pharmaceutically-produced products. In November of 2022, we had a major step forward with the FDA approval of a product called FMBL [fecal microbiota, live-jslm]. That is a treatment previously referred to as RBX2660 and this is under the class in the FDA of live biotherapeutic products, or LBPs.

This is the first product in this class. Our hope both in the C difficile world, and maybe eventually in the ulcerative colitis world, that we see microbiota altering treatments that can help patients prevent C difficile or minimize symptoms of ulcerative colitis, etc. This product is indicated in adults 18 and over for the prevention of recurrence of C difficile. You also asked where it fits in clinical practice. A product like this probably fits according to the guidelines, which is second recurrence and beyond. Within the guidelines for second recurrence and beyond it was felt both in the IDSA/SHEA guidelines and the ACG guidelines that there was significant benefit with fecal transplant so therefore we would stay with these live biotherapeutic products. In clinical practice, some of the LBP trials included patients with first recurrence. In patients with inflammatory bowel disease, it might be considered appropriate to use an LBP earlier in the treatment because we know the safety profile, we have open label study data in an IBD population. Therefore, it’s worth consideration for those patients that we’re fearful are going to get caught in that cycle of recurrence.

David Hudesman, MD: When we are seeing these patients in their first and second recurrences, do you take into account the time between the recurrences?

Paul Feuerstadt, MD, FACG, AGAF: That’s a really important question. C difficile treatment is not as organized as the IBD world. For the last 15 years, recurrences have been defined by 1 month, 2 months, or 3 months. The bezlotoxumab trials were 3 months, the fidaxomicin trial was 1 month, and the live biotherapeutic trials were 2 months. How do you sort this through?

Three months is relatively conservative. The majority of recurrence is happening within 1 month, but in clinical practice, the good rule of thumb is about 6 months. The microbiota turns over about every 90 days so if you’ve lasted 90 days, which I like to call the window of vulnerability, you’re much less likely to get a recurrence of C difficile. In 6 months, the microbiota has turned over twice. The likelihood that it’s the same C difficile infection or the same species of C difficile that is causing the symptoms goes down remarkably after 6 months. If somebody had C difficile 3 years ago and then they’re presenting again with C difficile, you start right back at the top. If somebody has C difficile and then 6 months and 1 day later gets a recurrence, I would treat that as first recurrence. If it’s 8 months to a year, then I would start back at the initial treatment algorithm.

David Hudesman, MD: We saw efficacy results around 70%. How long was there follow up? Was there good long term follow up looking at the microbiota in those patients? Was it just 2 months, or do we have longer follow up than that?

Paul Feuerstadt, MD, FACG, AGAF: LBP trials follow up for a minimum of 6 months. With the FMBL, that product in their phase 2 data had 2 years of safety follow up and sustained response follow up. In the pivotal phase 3 trial, the PUNCH CD3 [NCT03244644] trial, it was 6 months of follow up. Overall efficacy was 70.6% for FMBL versus placebo which was 57.5%.

Jordan Axelrad, MD, MPH: We commonly will encounter in practice patients who are put on a standard of care antibiotic while still persistently symptomatic. Sometimes, these patients may be referred to us for fecal transplant. Is there a way that you evaluate these patients that have sort of persistent symptoms through their therapies whether that’s truly recurrence of their PCR testing may not be reliable and so forth?

Paul Feuerstadt, MD, FACG, AGAF: About 25% of patients that come to see me with recurrent C difficile don’t have recurrent C difficile. Sometimes it’s a lack of understanding of diagnostic testing, but frequently it’s a situation that you actually just presented; the patient has resistant symptoms. What does that actually mean? The potency and efficacy of vancomycin and fidaxomicin for active infection is excellent. Any patient that is having resistant symptoms to either of those antimicrobials should be considered not to have C difficile. If they are on those antimicrobials and their bowel habits have not at least improved a little bit, we will use the confounder of inflammatory bowel disease. They should at least improve and come down maybe half as frequent in terms of frequency of bowels. It’s probably their underlying inflammatory bowel disease. In the real world, when patients come in and say, “I’m on vancomycin and I’m not responding,” it’s up to us as gastroenterologists to think through the differential diagnosis. Is this a post-infection irritable bowel syndrome [IBS] seen in about 25% of these patients? Is it inflammatory bowel disease? Is it a microscopic colitis? Is it some other medication-induced effect? Did they start on new medications? Have they traveled recently? It’s the usual suspects and then as gastroenterologists we have the power to do a colonoscopy and take a look and take some biopsies and see what’s going on. The majority of these patients are not resistant to the antimicrobials. It’s up to us to create that differential diagnosis and figure out what’s going on.

Jordan Axelrad, MD, MPH: That’s a really important conversation that I have with so many patients. These microbial therapeutics are for C difficile recurrence prevention. They are not a therapeutic necessarily for active C difficile infection, especially for recurrent episodes.

David Hudesman, MD: Do you ever recommend probiotics or prebiotics? We know what the guidelines say, but what are your thoughts?

Paul Feuerstadt, MD, FACG, AGAF: They are very controversial. I am a big probiotic proponent with the caveat that probiotics are supplements. Supplements have virtually no data associated with them. When you look at probiotics, the probiotic of choice is Saccharomyces boulardii for C difficile infection. Saccharomyces boulardii alters the metabolic environment within the colon to prevent inversion from spore phase to vegetative phase by altering the bile salt. There is basic science data that came out of Boston a number of years ago that showed that, and there is some clinical data that looked into it.

The ACG guidelines say the certainty of evidence is insufficient to recommend probiotics. The AGA position paper by Crytus et al from August 2021 also said the certainty of evidence is insufficient. My belief is that you’re not doing harm by giving probiotics. I do not use Saccharomyces boulardii after a fecal transplant. Fecal transplants give you the ultimate probiotic. I consider Saccharomyces boulardii in patients with a recurrence or multiple recurrences that we’ve cured with an antimicrobial alone to prevent recurrence in the future. If it is one recurrence I usually use about a month’s worth. If it is multiple recurrences I will use up to 3 months. There’s one population that we absolutely should never use a probiotic in and those are our patients who are severely immune compromised, ICU [intensive care unit], septic. There have been reports of fungemia from those probiotics, so we do need to be careful. I am a proponent of it, but I absolutely see the other side and the argument, and the certainty of evidence is insufficient right now to make a definitive statement.

David Hudesman, MD: Is there anybody that you will not or should not use an FMT in?

Paul Feuerstadt, MD, FACG, AGAF: There is a school of thought from Monika Fischer’s [MD, Indiana University Health] lab in Indiana that we can use FMT in patients that have fulminant disease. These patients are too sick to go to the [ED] and they have excellent results. There is not a safety signal that is overly concerning. I think the safety signals that have come up with regards to FMT over time are results of us learning appropriate screening and us learning the diagnostic tools that we discussed with C difficile. We also need to apply those diagnostic tools to screening of individuals who are donating for transplant and those individuals need to have both EIA and PCR assays. EIA is looking for whether they actually have an active infection, but PCR is looking for presence or absence of the bug. If we just transcribe the bug to somebody else, then it can reactivate in somebody else’s system and have failed the patient.

David Hudesman, MD: How are you using this recent FDA approved product in your office? How practically are you getting a patient this? Are you doing it in your office? Are you doing it at a center? Can they do it at home? Is that even an option?

Paul Feuerstadt, MD, FACG, AGAF: Doing it at home is not an option. It is incredibly easy to do in the office. It is a rectally instilled product, like an enema. It comes with a bag, a tube, a clip on the tube and a black circle at the end of the tube. If the patient has a recurrence, they take the full antimicrobial course. Then, there is what we call a washout period, where we want the antibiotics to wash out of the patient’s system. Vancomycin treats C difficile but can also cause it, so we want the patient to have 1 to 2 bowel movements before we administer the material. The patient comes to the office, they get gowned up, in any exam room they get into left lateral decubitis position. We lubricate the tube, insert the tube about 5 inches, open the clip, the material flows in. It’s about 150 cc that take about 2 minutes to flow in. We monitor the patient for another 5 minutes, and the patient can go on their way. This treatment is given after the standard of care antimicrobial.

One of the questions that comes up is infection control. All of these patients should have their symptoms completely controlled when they get a treatment like this or any form of fecal transplant because if they don’t, it is probably some other diagnosis. Remember, the vegetative phase needs to be controlled with that antibiotic before you can give that spore phase a knockout punch or you are not going to gain traction and reduce recurrence.

David Hudesman, MD: Anything you are excited for in the near-term future with C difficile management?

Paul Feuerstadt, MD, FACG, AGAF: We’re really on a precipice of greatness. FMBL was FDA approved, and then in April we are going to be hearing about another product, SER-109, which has also gone through phase 3 trials with positive results. Hopefully, for patients’ benefit, we will have multiple options for our patients to offer them so that we can shut down the cycle of recurrence. We’ve made so much progress in the last few years and we’re really at a great point right now. Thank you so much for having me.

David Hudesman, MD: Different practices, offices, and labs at our hospitals might have a preferential test. What are you doing in your office? And how do you break down colonization versus active infection?

Jordan Axelrad, MD, MPH: In the institution that we work at, we only have PCR testing available to us, so everything in life is clinical context. If a patient who had C difficile prior is presenting with new onset and watery diarrhea over 72 hours, this is a good predictor that if that PCR test is positive they have C difficile. The diagnostic uncertainty comes when patients may have intermittent symptoms or a concurrent underlying disease like IBS. We may need more detail to clinically differentiate active C difficile infection from an underlying disease such as Crohn’s [disease] or colitis. In that case, I will send patients for a GDH or EIA [assay] to help differentiate. Sometimes we will get a result back that says C difficile toxin PCR. That is still just a regular PCR test for C difficile. It is not a toxin assay, so you need that to say enzyme immunoassay to assess whether this is really toxin positive. Of course, if the presence of toxin is there you can feel fairly confident this is active C difficile infection.

David Hudesman, MD: I think the most important thing is who you’re testing. At our institution we have the PCR, and that’s what we have to use first line. Depending on my pretest probability I will decide if that is enough for me to treat that patient or if I am going to need to move forward. Do you recheck a C difficile toxin or C difficile PCR after treatment or if symptom resolution is good enough?

Jordan Axelrad, MD, MPH: No. So there is no indication to test for clinical cure. There are few instances where that may be useful, particularly if patients are going to be immunosuppressed such as chemotherapy or bone marrow transplant. There is really very little indication to check for a cure but because PCR testing is so sensitive you may be detecting dead C difficile that’s still lingering after a course of therapy. If there are new onset symptoms that’s a good indication to repeat testing but for cure not indicated.

David Hudesman, MD: Are you using vancomycin or fidaxomicin? Does this depend on insurance, or how sick the patient is?

Jordan Axelrad, MD, MPH: The IDSA updated recommendations to suggest that fidaxomicin may be used as a first-line standard of care antibiotic. I favor using fidaxomicin if I can get it from the patient’s insurance. If there is logistical issues, I want patients to get therapy as soon as possible so I am happy to use vancomycin. As Paul mentioned, both vancomycin and fidaxomicin are extremely good at treating C difficile. There’s no need to use higher doses of vancomycin, in particular for outpatients. I’m utilizing longer courses, in particular for our patients with IBS. I feel it works best for many of our patients.

David Hudesman, MD: I also use longer courses, at least 14 days and up to 30 days. That small study shows 30 days have lower recurrence rates, but nothing prospective. We are definitely more aggressive with our patients with inflammatory bowel disease and treat for longer. The same goes for other high-risk populations.

Jordan Axelrad, MD, MPH: If a patient is presenting with active, acute symptoms, their C difficile is positive, and they have evidence of high biomarkers of inflammation, I will generally treat both the C difficile and active IBD at the same time. I am not usually going to start with one and assess how things go. I think in a very sick patient it is safe to treat both.

David Hudesman, MD: I agree and that is probably one of the most common questions I get. Bottom line is you need to treat the C difficile aggressively. You need to treat the IBD aggressively. You get them both on board upfront. Retrospective data indicates you have better outcomes if you are treating both than if you are delaying appropriate IBD therapies.

Jordan Axelrad, MD, MPH: Agreed.

David Hudesman, MD: How do you think you’re going to be using this new product in the office?

Jordan Axelrad, MD, MPH: Early effective treatment is better for patients. I think we are going to be in the same place with C difficile therapies for patients at high risk of recurrence. If a patient does not have IBD but does have recurrent C difficile, you can do a pulsed course of vancomycin tapered over several weeks. Early fecal transplant or early microbial therapeutic is likely to provide a better benefit and less recurrence.

David Hudesman, MD: What we have learned in all of our patients with inflammatory bowel disease is earlier appropriate therapy is not only good for their short term, but also for better long-term outcomes.

One last practical question: What do you do about patients with C difficile who need to go on antibotics? Is there anything you use to prophylax?

Jordan Axelrad, MD, MPH: The first thing is to make sure that patient truly needs that antibiotic. I think that that is the most concerning thing is just to make sure. These patients need to have active infection. If they are seeing the dentist, we should call up the dentist to get some clarification on what’s going on. If they truly need an antibiotic, then patients at high risk should be prophylaxed for sure. We have the best data for vancomycin which is used 125 mg BID [twice a day] while they’re on their alternative antibiotic plus for 5 days after that antibiotic is treated. That helps to reduce the risk of recurrent C difficile.

David Hudesman, MD: Thank you so much. This was a great discussion on the future of C difficile management.

Jordan Axelrad, MD, MPH: Thanks, Dave.

Transcript Edited for Clarity