Infection Prevention Summer Reading

With apologizes to our colleagues in the Southern Hemisphere, many of us are traveling a bit this summer and are looking for good things to read. At the top of my reading list is Ed Yong's new book, "I Contain Multitudes: The Microbes Within Us and a Grander View of Life." The book by the highly regarded UK science journalist (The Atlantic, National Geographic) digs into the relationship between microbes and animals. Unfortunately, the book won't appear until August 9th, so you'll have to be a bit patient and find something else to read.

In the meantime, I've listed five recently published journal articles/studies that will hopefully tide you over until "I Contain Multitudes" appears at your bookstore.

1) A Flawed Revision of the Common Rule (Joffe and Magnus, Annals 19 July 2016). The Common Rule is the regulatory framework that guides human subjects research, think IRB. Last September, 16 federal agencies released a Notice of Proposed Rulemaking outlining proposed changes to the Common Rule. There are several potentially important changes that could negatively impact infection prevention and stewardship studies. First, the Notice seeks to redefine all research on biospecimens, including de-identified specimens, as human subject research requiring "broad consent" before storing the specimens. The discussion didn't mentioned microbiology specimens specifically, but this requirement is concerning. Second, the Notice would only exclude QI research from review if it analyzed proven interventions and limited study endpoints to utilization outcomes (e.g. cost). However, QI projects such as quasi-experimental studies of the impact of CLABSI checklists on BSI rates or mortality WOULD require IRB review and potentially individual informed consent. (Yikes!)  My sense is this could drastically curtail important research in MDRO prevention and most infection control research. Stay tuned.

2) Control of an Outbreak of Middle East Respiratory Syndrome in a Tertiary Hospital in Korea (Park GE et al. Annals, 19 July 2016). From May to July 2015, 186 confirmed cases of MERS-CoV occurred in S. Korea. The authors provide an in-depth description of a 92-person outbreak in a single tertiary-care hospital in Seoul. Interestingly, 82 of the cases occurred after exposure to a single secondary patient cared for in their emergency department. All cases were identified through contact tracing and monitoring of exposed patients and healthcare workers and all in-hospital transmission was secondary to three patients with pneumonia and productive cough. The description of events was very sobering.

3) Colonization With Methicillin-resistant Staphylococcus aureus and Risk for Infection Among Asymptomatic Athletes: A Systematic Review and Meta-analysis (Karanika S et al, CID 15 July 2016). The results of this study suggest that you shouldn't be an athlete (6% MRSA colonization rate), especially a wrestler (22% MRSA colonization rate). Additionally, the authors reported that colonization increases the risk of subsequent skin and soft tissue infection 7 times. If only it were safer to lay around on the beach this summer.

4) Addressing Infection Prevention and Control in the First U.S. Community Hospital to Care for Patients With Ebola Virus Disease: Context for National Recommendations and Future Strategies (Cummings KJ et al. Annals 5 July 2016). Authors from the CDC, Texas Health Presbyterian Hospital in Dallas and other other institutions describe the massive infection prevention response that followed the infection of two MICU nurses who cared for the index patient from Liberia. The responses included protocols for specimen handling, managing medical waste and standardized PPE with education and monitoring. Nothing particularly novel in 2016, but the article certainly highlights the massive efforts and costs associated with the N=1 response that was required because of a chronically underfunded public health and infection prevention infrastructure.

5) A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection (Khanna S et al. J Infect Dis 15 July 2016). The authors describe an alternative method to fecal transplants that could potentially avoid donor screening among other barriers. They tested SER-109, which is encapsulated spores captured from healthy human donor stool that was treated with ethanol to eliminate pathogens, for the prevention of recurrent CDI. The cohort of patients had to have had >3 CDI cases in the prior 12 months and a clinical response to antibiotic therapy for their current CDI episode immediately prior to dosing of SER-109. The 15 patients in cohort 1 received high-dose capsules (15 on day 0 and 15 on day 1) and 15 patients in cohort 2 received lower dose capsules on a single day. Overall, 87% achieved the endpoint of no CDI at 8 weeks. If you're interested in reading more, there is an excellent accompanying editorial.

The Power of Poop

If you needed even more reasons to move to Iowa, you now have another - an HAI-related Grand Rounds by esteemed co-blogger Mike. I might have gone with Tao of Poo(h), but who can ignore Poop's Power?

Update: Webcast (audio + slides) of the talk is now available.

Fecal transplantation: Not just for medical journals anymore

A new piece in the Atlantic by science writer Amanda Schaffer is the best article in the mainstream media on fecal transplantation that I have seen (and I think I've seen them all). She tackles a complex topic, makes it understandable without losing the nuance, and covers both the medical and regulatory aspects.

Another kibosh

Increasingly, my work life seems to revolve around C. diff. Yesterday I performed three fecal transplants. All were elderly patients who had been suffering with recurrent C. difficile for many months. Using stool from OpenBiome's stool bank greatly simplified my job and made the entire process much easier for the patients. Since OpenBiome's donors are extensively screened, the patients did not have to identify a donor and bear the unreimbursed costs of donor screening. Family members of all three patients commented on the ease of the process, and were quite happy with not having to identify a donor. The daughter of one patient who been transplanted previously with a directed donor, specifically commented on her preference for using a standard donor. And as always, the patients and family members were incredibly grateful and very happy to think about life without vancomycin. I left clinic feeling as though I had made a real difference by providing these patients a therapy that still is unfortunately relatively rare. One of the patients yesterday had to travel three hours to see me for this very simple, yet highly effective treatment.

Last night, on the way home, one of our infectious diseases fellows called me to discuss fecal transplant for a critically ill patient in the ICU who was failing all the drugs we have available to treat C. difficle. I happily told him that fecal transplant should not be a problem as we have frozen stool now available in the pharmacy.

This morning I spoke by phone with a woman whose mother is hospitalized two hours away after having multiple recurrences of C. difficile regarding coming to Richmond for transplant. And a patient that I transplanted a few weeks ago (the first patient I transplanted with donor stool from OpenBiome) called to tell me how well he was doing.

It seemed as though the whole fecal transplant process was finally working very smoothly. But as I went to bed last night, I took a final look at my phone and saw an email from a colleague with a link to new information from the FDA on fecal transplant. Those of you who follow this blog may recall that the FDA had previously proposed that all fecal transplants would require an IND number; however, this requirement was later relaxed. I was stunned by the FDA's proposed new rule. Since the FDA seems to write in a different language, I will paste their verbiage here:

After publication of the July 2013 Guidance, FDA has continued to review this area and is clarifying its enforcement policy.  FDA intends to exercise this discretion on an interim basis, provided that:

1. The licensed health care provider treating the patient obtains adequate informed consent from the patient or his or her legally authorized representative for the use of FMT products.  The informed consent should include, at a minimum, a statement that the use of FMT products to treat C. difficile is investigational and a discussion of its potential risks.
2. The FMT product is obtained from a donor known to either the patient or the treating licensed health care provider. 
3. The stool donor and stool are qualified by screening and testing performed under the direction of the licensed health care provider for the purpose of providing the FMT product to treat his or her patient.  

FDA does not intend to exercise enforcement discretion for the use of an FMT product when the FMT product is manufactured from the stool of a donor who is not known by either the patient or the licensed health care provider treating the patient, or when the donor and donor stool are not qualified under the direction of the treating licensed health care provider. 

So it seems that the FDA is not happy with the concept of banked stool from standard donors and would prefer directed donors. If I test a donor once for infections and that donor is known to the patient, I don't need an IND. But, if I obtain the stool from a stool bank that has a small number of highly selected donors that are tested serially every 60 days, and the stool is quarantined to avoid the problem of an infected donor in a seronegative window period, I need an IND? The blood bankers actually discourage the use of directed donors as the directed donor may be less likely to disclose risk factors for infectious diseases. There is no reason to think that would be different here.

I called the number on the FDA's announcement. The person I talked to was polite but I felt as if I was talking to someone in a parallel universe. After 10 minutes, I didn't feel like I had any better understanding of the issue. She told me that there were no data that fecal transplant is effective for C. difficile. Really? I reminded her that the randomized controlled trial published in the New England Journal was stopped early because it worked so well. She could not tell me whether I could even get an IND if I was using product from a stool bank, though later implied it could only be used in a clinical trial. She transferred me to "Manufacturing" and felt sure they could help me. The person in Manufacturing was not even aware of the announcement and said that I need to talk to someone in "Vaccines." Between this issue and the IV zanamivir issue, I have come to the conclusion that the FDA is so isolated and so sucked into the parallel universe of its bureaucracy that's it's lost touch with its mission.

While I might not be able to understand what the FDA is saying, here is what I do know: recurrent C. difficile is a terrible illness that is becoming increasingly common. In a subset of patients, antibiotics are not curative. It destroys quality of life, and if untreated in the elderly leads to wasting and ultimately death. A simple treatment is highly effective in curing the infection. And a group of really bright students in Boston found a creative solution to make stool transplants readily available and quite safe for patients. But a behemoth bureaucracy chooses to stand in the way.

Great news for patients with C. difficile

At this point in time, I've performed about 50 fecal transplants. I find these procedures to be both a blessing and a curse. They are amazingly effective for patients with recurrent C. difficile. Many of my patients have had chronic diarrhea for months, and are unable to leave their homes. So imagine how incredible it is for them to be cured within 24 hours of a fecal transplant. I have heard over and over, "you have given me back my life." And I have to admit it's a blessing for me, too. Rarely in medicine do we see such rapid and dramatic cures. What's not to like about this? How could it be a curse?

Well, as we have blogged before, the logistics of fecal transplantation are difficult and there are a number of barriers. While most patients don't have difficulty finding a donor (usually a family member), some elderly patients don't have a donor. Cost is also a barrier. Donor testing is not covered by insurance, so the out-of-pocket cost is up to $1500. For poor patients, this is quite a problem, and I've had patients whose family members all chipped in to pay for donor testing. Then the donor has to "perform" at a specified date and time (and sometimes they can't).

The transplant I did yesterday was fairly typical. I went to the clinic to pick up the donor specimen and ran it to the lab (10-15 minute round trip), where our laboratory technician began the dirty work of homogenizing the stool sample in a blender and filtering it. While she was doing that, I ran back to the clinic, got the informed consent, inserted the NG tube and sent the patient to X-ray for confirmation of tube placement. The queue in x-ray can be up to 45 minutes. While the patient was in X-ray, I ran back to the lab, picked up the prepared specimen and returned to clinic. When the patient returned, I injected the NG tube with the fecal slurry, flushed the tube with some water, then removed the tube. On most days, all of this takes 2-3 hours of my time. If insurance pays us, we collect less than $75. During the same time period, my colleagues will generate charges that are roughly 6-9 fold higher than mine. Since most of us now work in an RVU-based compensation model, it should be apparent why so few physicians do this work. But I can't not do it, even though it reduces my salary. I feel morally compelled to help these patients who are so desperate, particularly when I know that the odds are very high that I can cure them with a simple procedure.

Yesterday I stumbled on OpenBiome's website and as I explored it I was nearly euphoric. OpenBiome is a non-profit started by four students (a molecular biology PhD candidate, an MBA candidate, an MPA candidate, and an MD/MBA candidate) at Harvard, MIT and Princeton. The company provides processed, frozen human stool from donors that have been carefully selected and screened for multiple infectious diseases at least twice, at a cost that's 1/6 the price of me testing one donor, and 5 to 14-fold cheaper than the drugs that these patients have taken without success. And OpenBiome's goal is to reduce the price even more as they scale up their operation. I had a long conversation today with James Burgess from OpenBiome. He knew so much about C. diff that I assumed he was the medical student, but he's actually the MBA student. He was excited to tell me about their work and I was incredibly impressed. They have covered all the bases, including banking serum from donors for future testing should a patient develop an unusual infection.

So Kudos to OpenBiome! Many patients will benefit from their ingenuity and generosity. And they'll make my job a whole lot easier.

Word of the day: crapsule

There's a great article in The Atlantic on fecal transplants for C. difficile infection (free full text here). What I like about this piece is that it describes the very real barriers to fecal transplantation without any sugar coating. It also highlights the work of Dr. Bruce Hirsch, an infectious disease doctor who crafts capsules with fecal bacteria (or "crapsules" as he calls them) so that patients can be transplanted without an NG tube or colonoscopy.

Photo:  Salon.com

The donor perspective

Today's New York Times has an interesting essay on fecal transplantation with an interesting twist: it's written by a stool donor. The recipient has inflammatory bowel disease. While there is not much evidence regarding fecal transplant for inflammatory bowel disease at this point, there is growing interest. When one compares the safety profile of fecal transplant versus those of highly immunosuppressive therapies for IBD, it's easy to see why many patients might be willing to pursue fecal transplant. I recently spoke to an internist at an academic medical center, who told me that several of his gastroenterology colleagues are informally recommending to patients that fecal transplant may be worth pursuing for IBD. Oh, the power of poo...

Graphic: Katie Scott, New York Times

A pleasant surprise....

Yesterday, the FDA quietly posted an announcement regarding the requirement for submitting an investigational new drug (IND) application by physicians who perform fecal transplantation. In part, it says:

Some health care providers have stated that applying IND requirements will make FMT unavailable and have suggested that an alternative regulatory approach is needed to ensure the widespread availability of FMT for individuals with C. difficile infection unresponsive to standard therapies. 

The agency acknowledges these concerns and intends to exercise enforcement discretion regarding the IND requirements for the use of FMT to treat C. difficile infection not responding to standard therapies provided the treating physician obtains adequate informed consent from the patient or his or her legally authorized representative for the use of FMT products. Informed consent should include at a minimum, a statement that the use of FMT products to treat C. difficile is investigational and a discussion of its potential risks. 

FDA intends to exercise this discretion while the agency develops appropriate policies for the study and use of FMT products under IND. The agency intends to issue guidance reflecting the agency’s intention to exercise enforcement discretion.

During this time FDA strongly encourages compliance with the IND regulations, and stands ready to work with sponsors who are interested in conducting clinical trials.

I've read this a couple of times, and I'm not sure exactly what this means. Can fecal transplantation now be performed without an IND as long as there is informed consent? It sounds as though further information is forthcoming. Nonetheless, it appears to be a step in the right direction. Kudos to the patients and their families for making their voices heard. Yesterday, one of my patients spoke about her experience here:

NBC12.com - Richmond, VA News

FDA shoots self in the foot

Last week I blogged about the FDA's ruling to classify human stool as an investigational new drug, making it more difficult for patients with recurrent C. difficile infection to undergo fecal transplantation, an incredibly effective therapy.

I was scheduled to perform a fecal transplant on a patient this morning, but notified her a few weeks ago that we could not proceed because of the new ruling. She asked to keep the appointment with me anyway. She presented to clinic this morning and informed me that she had performed the transplant at home a few days ago. And she was happy to report that she was feeling much better!

As it turns out, I have at least 3 more patients in the process of preparing for self-administered fecal transplant at home. The instructions for doing so are readily available on the internet. I suspect this do-it-yourself movement will now become widespread. It's ironic that the attempt by the FDA to regulate this procedure in the interest of safety appears to be driving a completely unregulated and more risky response.

Someone should have reminded the FDA that unlike the usual investigational new drug, which is impossible to obtain outside of a highly regulated and structured mechanism, human stool is readily available, easy to procure, and impossible to regulate. These patients are highly motivated, know the data on effectiveness, and won't be told no!

Photo:  Vendor Alley

The kibosh

Over the past several days I have spent a lot of time talking to patients, trying to explain why I've had to cancel their upcoming fecal transplant. The FDA has ruled that stool is an investigational new drug (IND), which now imposes a huge bureaucratic hurdle to getting a much needed therapy for patients with recurrent or intractable C. difficile infection. Today's Omaha World-Herald covers the new ruling and features our fellow blogger Dan Diekema. 

Even before the FDA did this, there were already hurdles for patients who are really suffering a great deal. First, there are few physicians who are providing this therapy. I have had patients drive over 8 hours to come for a treatment that is quite primitive but amazingly effective. For the doctor it's time consuming and the reimbursement is very poor. Nonetheless, I have felt morally compelled to provide this therapy and as a result I have many thankful patients. Then there is the issue of insurance companies not covering the cost of donor testing, which costs $1500-2000. Now there's the additional burden of the FDA red tape and the numerous documents required by institutional review boards.

So now I must apply for an IND number, which requires that I send the FDA my protocol. On the 30th day after receipt of my documents the FDA will let me know whether I can proceed. When I talked to the FDA officer yesterday she informed me that the FDA is only interested in fecal transplants with regards to safety. They want to ensure that donors are appropriately screened. Thus, I need to send them my protocol for donor testing and then I will get a ruling. I asked the officer what the FDA was looking for and was told that they can't say but will either approve or not approve my protocol. Now wouldn't it have made more sense for the FDA to review the literature and consult experts about what optimal testing of donors and safeguards should be for the procedure and simply require practitioners to follow their guideline instead of the guess-what-I'm-thinking-and-wait-30-days game?

Ok, enough Debbie Downer. Now something positive: here's an article about a pathology resident at Emory University, Dr. Hunter Johnson, who goes beyond the call of duty and serves as a stool donor. In the article he talks about how important it is to perform on command. I learned that lesson the hard way. When I first starting performing fecal transplants, I explained to patients the important exclusions for donor selection, such as no recent foreign travel and no recent antibiotics. But I never thought to tell patients that choosing a donor who has problems with constipation is probably not a wise choice until the day the patient arrived for a transplant with his donor but with no stool specimen in hand. Constipation is now on my list of exclusion criteria for donors!

Photo of Dr. Hunter Johnson by Eric S. Lesser, NBC News.com

Hat tip: Kathy Kreutzer 

I love me some anaerobes!

The first case-control study I performed early in my hospital epidemiology fellowship at the University of Iowa was an examination of risk factors for VRE (vancomycin-resistant enterococcal) bloodstream infection in an outbreak among oncology and bone marrow transplant patients at a community hospital. Little was known about VRE at the time. One very strong risk factor emerged from my data: receiving an antibiotic that had significant activity against anaerobes. This 20-year old observation has since been replicated and subsequently proven in experimental animal models. In mice treated with anti-anaerobic drugs, VRE burden can rise to the point that these organisms constitute 99% of the bacteria in the gut. Although VRE are relatively nonvirulent organisms, in neutropenic hosts they can cause bloodstream infection following gut colonization and translocation across the intestinal mucosa.

Now comes a very interesting study from Memorial Sloan Kettering Cancer Center in this month's Infection and Immunity. The investigators induced VRE colonization in mice, then performed fecal transplantation using stool from untreated, noncolonized mice. Within 15 days VRE could not be recovered from the feces of the treated mice. They next determined that the presence of the obligate anaerobe Barnesiella in donor stool was most closely associated with the therapeutic effect. They then evaluated stool cultures of patients who had undergone allogeneic stem cell transplants and found that those patients harboring Barnesiella in their GI tracts were protected from having VRE domination of their fecal flora.

The authors put their findings into an interesting evolutionary perspective in the paper's discussion:

"Oxygen-intolerant bacteria have limited options on the earth’s surface, and the metazoan colon represents an essential, and for many anaerobic species, sole, sanctuary. Despite their density in the colon and their proximity to the bloodstream, obligate anaerobes rarely cause human disease and their survival depends on their host’s survival. Obligate anaerobes of the gut promote their host’s survival by limiting the expansion of oxygen-tolerant bacteria, which, by and large, are the subset containing most of the intestinal pathogens. Our results suggest that Barnesiella spp., by restricting the growth of VRE, regulate the composition of the microbiota and optimize host survival."

I always teach the medical students that after they read a paper they should ask themselves to identify the implications of the paper for their practice. In this case, I suspect the implication is that my future is filled with performing many, many more fecal transplants. Although the yuk factor is very high, reimbursement is bad, and the time input is significant, the powerful results and grateful patients make doing it truly worthwhile.

Photo:  Dr. Ella Barnes, British intestinal bacteriologist and namesake of the VRE conquistador.

Proof.

Finally, the purists out there who require demonstration of efficacy by a randomized clinical trial before attempting a novel therapy can now breathe a great sigh of relief. The New England Journal of Medicine has just published an RCT that demonstrates the clinical utility of fecal transplantation for C. difficile infection. In fact, fecal transplants worked so well that the trial was terminated early after an interim analysis.

Patients in the study all had C. difficile infection with at least one relapse. They were randomized to one of three study arms: (1) a 4-day course of oral vancomycin followed by bowel lavage then fecal transplant via nasoduodenal tube; (2) a 14-day course of oral vancomycin; or (3) oral vancomycin plus bowel lavage. In the transplant group, 13 of 16 patients were cured after 1 fecal infusion (2 of the remaining 3 were cured after a second infusion). In contrast only 4 of 13 in the vanco group, and 3 of 13 in the vanco plus lavage group were cured. Bottom line: fecal transplantation had an overall cure rate of 96%.

There remain two barriers for patients to access this highly effective therapy: (1) very few physicians perform the procedure, in part, I think, because there is no reimbursement despite the several person-hours required to prepare the fecal solution and administer it; and (2) insurance companies will not reimburse for donor testing, which costs approximately $1500.

So we've proven what we already knew. Now it's time to look at more interesting questions: does fecal transplantation work for irritable bowel syndrome and inflammatory bowel disease?

Graphic:  Andrea Levy, Cleveland Plain Dealer.

We Are All Microbe

Most of us probably think we're products of our parents and their parents and their parents' parents. That's certainly true, but their collective contributions are outnumbered 10:1 (100 trillion vs 10 trillion cells) by our microbiome. The Economist cover story from this week highlights the latest thinking around the microbiome and it's implications for science and medicine. They even mention that a "handful of doctors" use fecal transplants to treat C. difficile since transplanting a microbiome is easier than transplanting a kidney. Mike is one of the handful of those doctors. (note: Maryn McKenna's comment on Mike's post from 2 years ago is still one of my favorite) One of the more interesting paragraphs covers the potential use of antibiotics to positively manipulate the microbiome:

"One is more sophisticated deployment of the humble antibiotic, arguably the pharma industry’s most effective invention. At the moment antibiotics are used mainly to kill infections. In the future they might have a more subtle use—to manipulate the mix of bugs within a human, so that good bugs spread at the expense of bad ones."


Part 2: "The human microbiome: Me myself, us" goes into the significance of the microbiome in greater detail.

Friday feces blogging (part 5)

A year or so ago, I bought a new external hard drive for my computer (see photo). I marveled at its storage capacity--1 terabyte! That just seemed to be a huge amount of information. So I almost fell off the exercise bike today when I read a statistic in this month's issue of The Atlantic (free full text here) on the data capacity of human feces. According to Larry Smarr, a computer scientist who views the human body as a ginormous database:

"There are about 100 billion bacteria per gram (of stool). Each bacterium has DNA whose length is typically one to 10 megabases--call it 1 million bytes of information. This means human stool has a data capacity of 100,000 terabytes of information stored per gram."

Now to bring all of this home, you should know that I use 30 gm of stool for the fecal transplant procedure. So if my math is correct, I am instilling 3 million terabytes (or 3 exabytes) of information.That is nothing short of amazing!

Weekend wrap-up

I'm writing this from my porch on a warm Richmond evening, wrapping up a great holiday weekend with my wife. No clinical work for me this weekend, but did a lot of things--detailed my car, made a big batch of gazpacho, worked in the garden, played the piano, tried to figure out what to do about the yellow jacket nest in the yard, and went to the gym. You know, things that normal people do. It was a refreshing break from the hassles of arguing with insurance companies about why treating MAC pulmonary infection requires more than 5 days of clarithromycin, documenting,  documenting, and more documenting every fricking thing we do, and playing the regulatory compliance game (a game where no one tells you the rules but consultants remind you that what you did do was wrong).

To make the weekend even better, I received the following email from a patient with a 5-month history of relapsing C. difficile infection that I did a fecal transplant on several weeks ago (she graciously allowed me to share it):

Wanted to let you know that it has been a couple of weeks since the transplant and I am back to my old self. My energy is back and so far I'm feeling terrific. Thank you so much for everything you and your staff did to help me. Everyone was so friendly and competent. I want to especially thank your nurse who did a great job in getting me to relax during the (nasogastric) intubation, which was the most uncomfortable part. It feels wonderful not to have to take any more antibiotics. I wish for you and your staff the very best and I hope that this procedure continues to help more and more people who have been going through this debilitating disease. Words cannot express adequately how grateful I am.

Emails like this one serve as a great reminder of why I went to medical school. And it helps to put the bucket of broken into perspective.

As I sit here watching a great blue heron fly over the James River, I can only think that tonight it's all good. Tomorrow, back to the grind!

Graphic:  Anna DeStefano

Reducing barriers to fecal microbiota transplant (FMT)

It is now conventional wisdom that FMT (a.k.a. “stool transplant”, “transfaunation”) is effective treatment for recurrent C. difficile disease. So why aren’t more being done? Many centers, including ours, have stumbled upon two barriers: the ick factor, and the logistics of patient-identified donor selection and screening. Not everyone can identify a willing donor, and there is no easy way to pay for the expensive set of screening lab tests performed on the donor.

So these two reports, which describe moving from patient-identified to universal volunteer donors, are welcome. One of the reports, out of the University of Minnesota, also examines the use of frozen, banked fecal material. In the absence of progress in replicating the fecal microbiome in culture, I think this is the best way to make FMT more universally available.

Don’t worry, I don’t think we’ll be staging “stool drives” in the future, like we do blood drives now. A single universal donor could provide all the stool required by a single center to treat multiple patients with C. difficile, and could be called back whenever the bank was running low (“Honey, it’s the clinic calling, they need more of your sh**”).

If you don’t have subscription access to the articles above, here is a short summary from the IDSA newsletter.

Image from www.zazzle.com

Stephen Colbert on chickenpox lollipops and fecal transplants

The Colbert Report	Mon - Thurs 11:30pm / 10:30c
Cheating Death - Chicken Pox Lollipops & Fecal Transplants
www.colbertnation.com
Colbert Report Full Episodes Political Humor & Satire Blog Video Archive

More on fecal transplants

Maryn McKenna has two new pieces on fecal transplants on her blog and in the latest issue of Scientific American (full text here). These are very well written. I plan to use these for patient education when I see patients with recurrent Clostridium difficile infection for whom fecal transplantation may be an option.

Addendum (2/1/12):  Click here to listen to an interview with Maryn McKenna on the topic of fecal transplants.

Don't poo-poo it!

Photo: People's Pharmacy

There's a new systematic review in Clinical Infectious Diseases on intestinal microbiota transplantation (AKA stool or fecal transplantation) for Clostridium difficile infection. In scouring the literature, the authors found reports of 317 patients who had received this treatment with an overall success rate of 92% and no attributable adverse effects.

Stool transplantation was first performed in a human in 1958; however, veterinarians have used this treatment for hundreds of years in treating horses with chronic diarrhea. The vets call it "transfaunation," which I think sounds better than what we call it.

I first became interested in this treatment when I began getting patients referred to me who had had numerous episodes of C. difficile infection over long periods of time despite treatment with every known pharmacologic intervention. I've now done 10 or so transplant procedures. Unfortunately, the systematic review does not describe the duration of diarrhea that patients endured prior to transplantation, but in my experience, patients have often had diarrhea for months. A few months ago, I successfully transplanted a patient who had diarrhea for six years every time oral vancomycin was discontinued. And what's most amazing about this treatment is the rapidity of its effect--most patients have resolution of symptoms within 24 hours. One patient called me to say that she screamed with delight on having her first normal bowel movement in 6 months just 1 day after her transplant.

When I explain the procedure to patients, I always give them the option of doing the procedure themselves at home (a DIY paper was published last year), but when I get to the part about the blender, the patient invariably cuts me off with a big "NO!".

There are still skeptics, however. The purists say they would never perform such a procedure without results of a randomized controlled trial reporting effectiveness. Of course, publication bias may be at play here, making the procedure appear more effective than it truly is. But I think that being a good doctor sometimes forces you to confront the limits of evidence, step outside of your comfort zone, and try a therapy that's cheap (particularly when you consider that a 2-week course of oral vancomycin costs about $2000), probably effective, and safe when appropriate precautions are taken. And there's an argument to be made that when a treatment has a dramatic effect (a rapid response on a stable background), the risk of bias accounting for that effect is very low.

For those of you who want to read more, there's an excellent, recently published, perspective piece in Clinical Gastroenterology and Hepatology that nicely reviews the rationale and methods for performing the procedure.

A more cultured approach to fecal transplant?

Mike recently blogged about the increasing interest in fecal transplant for severe and/or refractory Clostridium difficile associated disease (CDAD). The procedure remains very slow to catch on, though. Why? The lack of a controlled trial is certainly one reason, but the other is simply the “ick” factor. The ick factor, and the difficulty in controlling a trial when another person’s stool is the deliverable, is also one reason why controlled trials have been slow to come.

If only one could replicate the stool microbiome using culture techniques, this barrier would exist no longer. However, early studies of the gut microbiome revealed that the majority of species are not cultivatable in the laboratory.

So I found this report from Washington University to be very interesting—these researchers were able to preserve gut microbiome functions in germ-free mice using strict anaerobic culture techniques. If indeed a person’s “readily cultured bacterial community” could exhibit in vivo behavior that mirrors the complete microbiome, then there is the potential for complex microbial communities to be developed and passaged that could replenish the microbiome in patients with CDAD.