
Alternative treatment shows promise against risky infection
Transcript
Host Amber Smith: Upstate Medical University in Syracuse, New York, invites you to be The Informed Patient, with the podcast that features experts from Central New York's only academic medical center.
I'm your host, Amber Smith.
An Upstate doctor did research that shows a better way of treating a life-threatening diarrheal illness, and he's here to tell us about it. Dr. Aamer Imdad is an assistant professor of pediatrics, and he specializes in nutrition and pediatric gastroenterology.
Welcome back to "The Informed Patient," Dr. Imdad.
Aamer Imdad, MBBS: A pleasure. Thank you.
Host Amber Smith: I'd like to start by having you tell us about this diarrheal illness that can be so severe. What's it called?
Aamer Imdad, MBBS: The name of the infection is Clostridioides difficile. It used to be called Clostridium difficile. In short we call it "C. diff."
It's an infection that can cause diarrhea because of inflammation in the colon, which is the large bowel.
Host Amber Smith: Where does C. diff come from? How does somebody get it? ,
Aamer Imdad, MBBS: Many of us actually have C. diff in our large bowel. The C. diff infection happens when the balance of good bacteria versus bad bacteria kills towards the bad bacteria, so it is present in the form of spores, so it can survive for a longer period of time.
And as it gets the opportunity to grow faster and produce a toxin, that can lead to the illness, which could be very severe, especially in older people.
Host Amber Smith: Is that why it can be potentially life-threatening? Is it mostly for older people or people with compromised immunity?
Aamer Imdad, MBBS: To a certain extent. So, it can happen in immunocompetent patients as well. So, what we have seen over time is that it is actually the most common gut-associated infection acquired from the hospitals, so it's more likely to happen in patients who have been admitted in the hospital for a longer period of time. We have also seen patients getting this infection in the community as well, and we have seen it in children, young adults and then adults in old age as well.
It tends to be more severe in patients in older age, but it can happen at any age beyond the childhood period.
Host Amber Smith: And how is it usually treated?
Aamer Imdad, MBBS: We can actually go back and kind of say, why does it happen at the first place? So the most common reason for having C. diff infection is use of antibiotics.
Most of the time, a patient will go on antibiotics for reasons, let's say, pneumonia or urinary tract infection, or, in children, for example, they could be treated for ear infection. And that not only kills the bacteria that was causing that infection, but it also kills the good bacteria in the gut, and that gives an opportunity for the C. diff to grow, leading to infection.
So, once somebody has diarrhea, and they get tested positive for C. diff, the initial recommendation is to treat the C. diff infection with antibiotics. And there are certain types of antibiotics that work better for C. diff compared to some of the other antibiotics.
What we discovered over time is that even though these antibiotics could be effective in treating C. diff infection, they actually increase the risk of having another infection because the very first infection happened because of use of antibiotics. So then we use the antibiotics to treat the infection of C. diff, but that exacerbates the imbalance of good versus bad bacteria, leading to risk of another infection.
So, if we talk in percent risk, if a person has a C. diff infection for the first time in their life, there's about a 25% chance that they will have another one. But if they get treated for that other one with antibiotics, the chances of having another one is about 40%. And if you have C. diff two times, the chances of getting a third is about 60%, which is really high.
So it's very important to kind of understand that we think the antibiotics not only help treat, but behind the scenes, it may actually exacerbate the problem in the long term.
Host Amber Smith: So it doesn't sound like it's the best solution.
Aamer Imdad, MBBS: Indeed.
Host Amber Smith: Is that what prompted you to consider or look at stool transplants?
Aamer Imdad, MBBS: Indeed. Stool transplant helps us to break that cycle, where there is an imbalance of good bacteria versus bad bacteria. There's a term called "dysbiosis" for that. Dysbiosis happens when you use antibiotics for any reason, and that dysbiosis can increase the risk of C. diff infection, and once C. diff infection gets treated with antibiotics, that dysbiosis continues to worsen.
Fecal microbiota transplantation, or stool transplantation, reverses that dysbiosis because we essentially take the stool from a healthy person who does not have dysbiosis, and we transplant that to a patient who seems to have dysbiosis and is getting these C. diff infections because of that.
Host Amber Smith: That's very interesting.
So, healthy people have a microbiome that's " even" -- you have good bacteria and bad bacteria, but they're in a better state?
Aamer Imdad, MBBS: Yeah, this area of research is expanding, and we're getting to know more and more about how the microbes in our body kind of interact with us.
We have bacteria in our gut. We actually have fungi in our gut. We also have viruses in our gut, as well, that live very happily with our body and not only live happily, but actually produce a lot of useful things that really help our body do its functions. Some of the bacteria, for example, are involved in some of the vitamin productions, hormone productions in the gut.
What has been noticed over time is that if there is an imbalance, either in terms of the number of the good bacteria versus bad bacteria, the type of good bacteria versus bad bacteria, and then an absolute ratio between them.
So, we are working more and more to get to know exactly what kind of imbalance would increase the risk. But initial data does show that at least for risk of C. diff infection, there is a very noticeable imbalance of bacteria in our gut that increases the risk and gives the opportunity for C. diff to grow and cause the C. diff-associated diarrhea.
Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith.
Host Amber Smith: I'm talking with Dr. Aamer Imdad. He's an assistant professor of pediatrics at Upstate, where he specializes in nutrition and pediatric gastroenterology, and we're talking about research he published recently showing that stool transplants do a much better job treating C. diff infections than the commonly used antibiotics.
So can you tell us about the study you did?
Aamer Imdad, MBBS: We did a study called a systematic interview and meta-analysis, under Cochrane Collaboration.
Cochrane Collaboration is a group of experts that help synthesize all the available evidence for a particular health care intervention. Cochrane Collaboration helps produce the Cochrane Reviews that are in Cochrane Library, and we all have access to that library. It is considered the gold-standard piece of evidence synthesis that typically leads into a final say in how the clinicians are going to practice.
So, for example, our work from these two Cochrane Reviews will be used by American Gastroenterology Association to issue their guidelines. It feeds into how the clinicians practice.
So, the process starts with a clinical question. We, as clinicians, were very interested to know that if patients are getting recurrent C. diff infection, can the stool transplant be helpful?
So, scientifically, in order to answer that clinical question, the best type of evidence comes from randomized control trials where patients with that particular condition are randomized into either, say, in this case, a fecal microbiota transplantation, or stool transplantation, versus the standard of care.
So, once the results are available from more than one randomized control trial, they can be synthesized quantitatively or mathematically into meta-analysis, giving us a summary estimate that will indicate the final efficacy, or effectiveness, of the intervention to help us guide our clinical practice.
In this particular study, we found that fecal microbiota transplantation, or stool transplantation, helped resolve the recurrent C. diff infection more often than the standard-of-care antibiotics.
Host Amber Smith: So, based on your findings, would patients with C. diff infections be candidates for stool transplants, or would you only recommend it for someone who has recurring C. diff infections?
Aamer Imdad, MBBS: This is a very good question and a very important one to differentiate. Our study looked at prevention of recurrent C. diff, so the stool transplant will be done in between the episodes. So, for example, if a patient had one episode of C. diff, and then they had another one, and then they had another one, and it keeps happening, typically within one to two months of the previous infection.
Not only that, it can cause illness, obviously it can also affect the quality of life in terms of the number of days somebody could be sick, or they could be admitted (to a hospital) because of the infection. So, the stool transplant is helpful to break that cycle and is done in between the episodes, when the patient is not having active symptoms.
Host Amber Smith: So, at this moment, are stool transplants readily available, and does health insurance pay for them for this?
Aamer Imdad, MBBS: There are very important advancements that have happened over the last few weeks, actually. Historically, there were stool banks in the country that were collecting the stool specimens from the donors, screening them for common infections and then freezing them and then transporting them to the facilities where they could be transplanted.
And Upstate is one of those sites, and I myself, and my colleagues here in pediatrics and in adult gastroenterology have performed the stool transplant. Now, more recently, FDA has approved a stool transplant product. I won't take the name here, but it was approved, that could be delivered via enema, and because it is FDA approved, it will most likely be covered by insurance as well.
Host Amber Smith: I was going to ask you how, practically, the stool transplants are done. So there are stool banks, so people make donations, and then the stool is processed. Is each stool transplant from one person, or is it blended from a bunch of people?
Aamer Imdad, MBBS: So, for the purpose of treating recurrent C. diff infection, a stool coming from a single donor is effective in most of the patients, and we typically do not have to mix the stool from multiple donors. There are some additional studies going on, and we have looked, in a separate, systematic review and meta-analysis, on the effectiveness of stool transplant for treatment of inflammatory bowel disease.
And over there it seems like stool donation from multiple donors will be required, for them to be pooled, to increase the richness and diversity of the bacteria in the stool. And it might have to be given more often compared to a one or maximum two to three doses for treatment of recurrent C. diff. So for the purpose of treating recurrent C. diff, it's typically a single-donor stool specimen, and that is transplanted into a single person.
Host Amber Smith: And you mentioned that it's transplanted via enema. Are patients hospitalized for this, or is that done in an outpatient setting?
Aamer Imdad, MBBS: Stool transplant can be done in multiple ways. So now there are actually capsules or "poop pills" that could be taken. It can also be administered through a nasogastric tube, which goes from the nose into the stomach, or nasoduodendal tube, which goes from the nose into the first part of the small bowel.
It could also be given via the enema.
And historically, it was initially started by giving it via colonoscopy, in which a colonoscope is taken to the very start of the large bowel. And it is distributed from start of the large bowel towards the end of it.
The pills and the enemas obviously can be done as an outpatient. For a colonoscopy, the patient typically has to come to the hospital, or at least an outpatient GI (gastrointestinal) clinic, where the colonoscopies could be performed.
Host Amber Smith: How quickly might a patient feel better after this?
Aamer Imdad, MBBS: It is a very effective therapy.
The key here is to understand that it is done when the patient is asymptomatic. So, the efficacy of a single microbiota transplantation is somewhere around 75%. So, if the patients have another recurrence, and they get a second transplant, the efficacy goes up to 90 to 92%, and there are very few interventions in medicine that are as effective as fecal microbiota transplantation for treatment of recurrent C. diff.
Host Amber Smith: Are there any side effects to watch out for from the transplant?
Aamer Imdad, MBBS: Remember, the stool is a donor-based stool specimen, and obviously, it not only has the good bacteria, it also has the bad bacteria. So there is a risk of transmission of infection, and FDA has issued some warnings about the possibilities of transmission of infection, including the COVID-19 infection, the monkeypox infection, which are both rare, but then there are other types of infection, and especially the patients who are immunocompromised, severely immunocompromised, they could acquire infection from the donor-based stool.
So, as part of the processing of the stool, all of the stool specimens are screened for common infections. And not only that, the donors are also screened for other health conditions. For example, if the donors have diabetes or hypertension or any other chronic disease, their stool will not be taken as a donation for the transplantation.
Host Amber Smith: So, it sounds like there's a structure to it, like the blood banking in the U.S., where the blood is surveyed before it's used.
Aamer Imdad, MBBS: It is.
It is less regulated compared to, blood donation, but we're probably moving towards that. Currently, there is not a very universal donor-screening protocol that we have, but we will most likely see that there will be guidance from organizations like FDA to help establish and run the stool banks as we gather more and more evidence for the usefulness of fecal microbiota transplantation for not only C. diff, but other conditions as well.
Host Amber Smith: I was going to ask if stool transplants can be used to treat C. diff, are there potentially other uses, too?
Aamer Imdad, MBBS: Indeed there are, and there is a lot of interest in studying the stool transplantation for other health conditions. And we as gastroenterologists are very interested in its use for treatment of inflammatory bowel disease.
So we did a sister publication on it where we looked at patients who have ulcerative colitis, which is one subtype of inflammatory bowel disease, and patients who are having active disease, can the stool transplant be used for their treatment?
And the data is actually very promising. It's not where we can recommend it for change of practice, but more and more studies are being conducted, and over the next two to five years, it is likely that we will have some sort of a conclusive evidence to say if the stool transplantation can be used for the treatment of active ulcerative colitis.
People are also looking at other conditions, like irritable bowel syndrome, obesity and beyond. Frankly, a lot of basic science data is finding association on how our gut microbes interact with our rest of the body. And a lot of scientists now think that some of the conditions that we experience in our body could be associated on how, and what kind of, microbes do we have in our gut.
Host Amber Smith: Well, this is very interesting work. I appreciate you telling us about it, Dr. Imdad.
Aamer Imdad, MBBS: Absolutely. My pleasure.
Host Amber Smith: My guest has been Dr. Aamer Imdad. He's an assistant professor of pediatrics, specializing in nutrition and pediatric gastroenterology.
"The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe.
Find our archive of previous episodes at upstate.edu/informed.
This is your host, Amber Smith, thanking you for listening.