During these unprecedented times, we understand the patient’s frustration and how this pandemic has created a halt to the readily accessible alternative treatment option in the FMT community. The need for continued treatments for a C. diff. infection and recurrent C. diff. infections are real and necessary. We also understand how patients experiencing
recurrent C. difficile infections are desperately seeking the FMT alternative treatment.
C Diff Foundation is able to provide information about treatments available to safely treat CDI’s and recurrent C. diff. infections.
Most home remedies or natural therapies, though, haven’t been put through the same rigorous clinical testing you expect from pharmaceutical medications.
In a world where you can fix almost anything with a do-it-yourself video on YouTube, you might think curing your own illness would be a piece of cake. It might be if it weren’t for a couple of (not so small) sticking points. One, the home remedy recommended by your friend — or one of the many websites promoting “natural therapies” — might not work.1 Dr. Harriet Hall, a retired family physician, former Air Force flight surgeon, and author of the SkepDoc column in Skeptic magazine, is one of those leading the charge against medical “treatments” not supported by science. Like others in the medical and scientific community, ……. There is the only medicine that has been tested and proven to work, and medicine that hasn’t,” Hall told Healthline. 1
Responses to an anonymous online questionnaire of 496 parents, researchers at the Cohen Children’s Medical Center of New York reported that 48 percent of the parents surveyed said they’ve held onto leftover antibiotics. More troubling to researchers was that of those parents, 73 percent reported giving those antibiotics to siblings, unrelated children, and unrelated adults. This would sometimes occur months after the drugs were originally prescribed. Dr. Ruth Milanaik, director of the neonatal neurodevelopment follow-up program at Cohen and senior author of the study, says the results show an “alarming” percentage of parents engaging in sharing or borrowing antibiotics, a practice known as prescription diversion. “This is dangerous not only for those given antibiotics that weren’t prescribed for them but for entire populations of people who some antibiotics may no longer help when the bacteria they target become resistant to them,” Milanaik said in a statement. 2
Discuss Resources available.
Times are trying during these unprecedented times and you are not without hope – we would like to help you and not see you get hurt or even worse. Please take time to speak to your treating physician and consider contacting a C Diff Foundation Triage Nurse at 727-205-3922 to learn more about safe and effective treatments available and options available to you at this time of desperation.
Remember – You Are Not Out of Options.
Stay safe – and please – Do NOT take medicine into your own hands.
With over 260 archived episodes ~ Listen At Your Leisure
It’s a new year with an entirely new line up of guests eager to share their C. difficile research, infection prevention methods, clinical trials in progress, the updates in the C. diff. community, and much more.
In March the post-Patient and Family Symposium presentations will broadcast, in the event you weren’t able to attend the live-online event hosted on January 15th. The first annual Patient and Family Symposium was sponsored by Seres Therapeutics
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“None of us can do this alone ~ All of us can do this together.”
For example, new data published in The New England Journal of Medicine underscore the shortcomings of advances in testing technology, suggested Sahil Khanna, MBBS, an associate professor of medicine at Mayo Clinic College of Medicine and Science, in Rochester, Minn. (2020;382:1320-1330).
At first glance, the study, which used data from 10 sites nationwide to derive a national estimate of the incidence of CDI, reported a relatively unchanged rate of the disease over a six-year period: 476,400 cases in 2011 and 462,100 cases in 2017. However, Dr. Khanna noted that after adjusting for the increasing use of nucleic acid amplification testing (NAAT), the researchers concluded that the incidence of CDI had actually decreased by 24% during the study period, including a 36% drop in healthcare-acquired CDI cases.
The study highlights a problem with NAAT, according to Khanna.
“NAAT is approximately 95% sensitive in detecting the C. difficile gene, but it cannot determine if the gene is active and toxin-producing, so it has the potential for overdiagnosis and for producing clinical false positives,” he explained. “Because of this, it’s important that we interpret NAAT results in the context of patient symptoms.”
Clinicians must be selective when deciding which patients should be tested, he said, only using it in patients who have acute diarrhea with no obvious alternative explanation, and who have the risk factors for CDI. These include older age, longer hospitalization, immunosuppression, use of antibiotics, gastric acid-suppressing agents, gastrointestinal surgery, manipulation of the gastrointestinal tract, and tube feeding.
“Patients not experiencing an active infection can be colonized with C. difficile, in which case there is a risk of a clinical false positives and unnecessary treatment,” Khanna emphasized.
An alternative testing approach now recommended by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) is the use of a multistep algorithm including glutamate dehydrogenase (GDH) to identify pathogenic bacteria and enzyme immunoassay (EIA) to detect C. difficile toxin (Clin Infect Dis 2018;66:e1-e48). NAAT should be reserved for instances in which results from GDH and EIA are inconclusive, the guidelines recommend.
“Unfortunately, NAAT remains the most commonly used test method,” Khanna said, adding that laboratories are increasingly adopting a two-step protocol of GDH and EIA.
Recurrent CDI mostly occurs in people:65 and older who take antibiotics and receive medical care
staying in hospitals and nursing homes for a long time with weakened immune systems
The treatment landscape for CDI also has changed over the past few years, noted Kim Ly, PharmD, a clinical pharmacy specialist in critical care and infectious diseases at Sunrise Hospital and Medical Center, in Las Vegas. Bezlotoxumab (Zinplava, Merck), a monoclonal antibody, is now approved for combination treatment of toxin B–producing CDI, along with an established antibiotic. Additionally, metronidazole, while still approved for the treatment of CDI, is no longer recommended by IDSA/SHEA as a first-line agent for primary CDI in adults.
“For severe initial episodes of CDI, oral vancomycin and fidaxomicin [Dificid, Merck] are now the preferred agents, and metronidazole is only recommended for nonsevere initial episodes when patients are unable to be treated with oral vancomycin or fidaxomicin,” Kim explained.
For a first recurrence of CDI, the IDSA/SHEA guidelines recommend administering oral vancomycin as a tapered and pulsed regimen or fidaxomicin, rather than a standard 10-day course of vancomycin. For subsequent recurrences, clinicians can use the same regimen, with the addition of a standard course of oral vancomycin followed by rifaximin or fecal microbiota transplantation (FMT).
Metronidazole comes into play again in the management of fulminant CDI, Ly noted.
“The IDSA/SHEA guidelines recommend treating this with oral or rectal vancomycin 500 mg four times daily along with intravenous metronidazole,” she explained.
Given that antibiotic-induced microbiota disruption “is far and away the number one precipitant for getting recurrent CDI,” selecting the CDI treatment with the least impact on the microbiota is important, said former IDSA president Cynthia Sears, MD, a professor in the Department of Medicine, Division of Infectious Diseases, at the Johns Hopkins University School of Medicine, in Baltimore.
“Vancomycin is the most commonly used therapy for CDI and its recurrences, but it decreases intestinal diversity and so impedes the recovery of the normal microbiota after CDI, setting the stage for CDI recurrence,” Sears said. “We have learned that vancomycin hits the colon with full force when taken orally because it is not absorbed, and it has off-target effects on lots of anaerobic bacteria that are essential to intestinal resistance of CDI.”
Fidaxomicin has less of an effect on the microbiota and has been shown to sometimes decrease the risk for CDI recurrence when compared with vancomycin (N Engl J Med 2011;364:422-431), but it can be expensive, she said.
Fecal Microbiota Transplantation
FMT is a less expensive, highly effective treatment that has received increasingly widespread attention, specifically for the management of recurrent CDI. Despite the enthusiasm surrounding the treatment, Sears expressed significant reservations about employing it.
“While there’s no question that FMT benefits patients with recurrent CDI, I feel we don’t yet have a quality-controlled product that we know is safe as well as being effective,” she said.
Sears pointed to two recent FDA safety alerts that warned of the harm that FMT can cause. The first, from 2019, reported that stool from a single donor had not been thoroughly screened before FMT and contained extended-spectrum ss-lactamase–producing Escherichia coli. The specimen had been used in separate FMTs for two immunocompromised patients, leading to infection with the pathogen and death in one case.
In another FDA safety alert from earlier this year, the organization said a stool bank specimen that had undergone comprehensive screening nevertheless contained enteropathogenic E. coli and Shiga toxin-producing E. coli. Transfer of the stool for the treatment of recurrent CDI resulted in one nonfatal infection and one death.
“Stool banks try very hard to be sure their specimens are free of disease-causing microbes, but if you have very low-level colonization, molecular diagnostics can miss this,” Sears said. More recently, she noted, the FDA has also raised concerns about the possibility of transferring SARS-CoV-2 through FMT, given that the virus can be present in the stool of infected individuals.
What would a safer and equally effective microbiota-based treatment look like? According to Sears, while microbial diversity seems to be protective against recurrent CDI, there are suggestions that the administration of specific strains may be able to treat CDI and can be produced under the same strict quality control manufacturing processes as other FDA-approved drugs. One study published in 2015 using human and mouse samples found that colonization with Clostridium scindens, a strain of Firmicutes, increased resistance to CDI (Nature 2015;517:205-208). Many microbiota-based therapeutics are in the research pipeline as well.
“I am optimistic that we will see something emerge that’s safer and still as effective as FMT for patients, whether it’s an orally or rectally administered product,” Sears said.
A new study published online in the journal ClinicalInfectious Diseases looked at the use of a non-frozen capsule of microbiome restoration therapy for treating patients with recurrent C. difficile infection.
“Patients with C. difficile are typically managed with antibiotics or fecal transplantation for recurrent C. difficile,” says the study’s author, Sahil Khanna, M.B.B.S., a gastroenterologist at Mayo Clinic. Dr. Khanna says fecal transplantation has been demonstrated to have high success rates by restoring the gut microbiome of patients. However, he says there are several challenges with fecal transplantation including standardization of the product, keeping it frozen, and mitigating the risk of infectious disease transmission during the procedure.
To help reduce the risks, Dr. Khanna and his team studied a transplantation method using a non-frozen capsule instead of whole stool transplantation. An initial dose-finding, the investigator-initiated study looked at the efficacy of different doses of fecal matter and the safety of performing microbiome restoration therapy using an oral product, RBX7455 developed by Rebiotix, Inc. The team found no concerns related to safety.
“Our study has several implications,” says Dr. Khanna. “We think that products like capsules may be able to replace fecal transplantation that is currently done via a colonoscopy. We also think that products that are non-frozen may allow for repeat dosing and for patient-administered self-treatment at home. The good news is that we are moving closer to having safe and effective products to restore the gut microbiome for patients with recurrent C. difficile.”
Dr. Khanna says that larger clinical trials and blinded, placebo-controlled trials are the next step in moving this potential treatment from research into practice.