Category Archives: C diff Treatments

American College of Gastroenterology Issued New Guidelines On Management Of Clostridioides difficile (C. diff., C. difficile, CDI)

The American College of Gastroenterology has issued new guidelines on the management of Clostridioides difficile infection (CDI), with recommendations reflecting developments from the availability of biologics to the growing use of fecal microbiota transplantation (FMT).

“These guidelines are a step forward in our understanding of C. difficile,” commented Sahil Khanna, MBBS, MS, a professor of medicine at Mayo Clinic in Rochester, Minn., who was not involved in the guideline development.

“For the practicing provider, there are some big changes in the treatment and testing of the disease,” Dr. Khanna said. For example, although the 2013 ACG guidelines on the topic recommended metronidazole or vancomycin for treatment of a first mild to moderate episode of CDI, he said, the new guidelines now suggest vancomycin or fidaxomicin (Dificid, Merck) for a first episode of non-fulminant CDI. Metronidazole now is suggested only as treatment for initial non-severe CDI in very low-risk patients.

“Metronidazole has already been on the decline in clinical use, and I think these guidelines will lead to further reduction of its use,” Dr. Khanna said.

A notable update in the new guidelines is a recommendation that bezlotoxumab (Zinplava, Merck) be considered for the prevention of CDI recurrence in patients at high risk for recurrence, he said. “This is the first time bezlotoxumab has made it into a major society guideline for the gastroenterology and infectious disease community, and I think it will help get the drug covered more often by payors and make it available more widely to the practicing clinician.”

ACG 2021
Annual Scientific Meeting & Postgraduate Course

The Premier GI Clinical Meeting
& Postgraduate Course

October 22-27, 2021 • Mandalay Bay

Another update that reflects the evolving body of evidence that has emerged over the past several years is a strong recommendation that FMT be considered for use after two CDI recurrences, or in patients with severe and fulminant CDI refractory to antibiotic therapy, particularly when they are poor surgical candidates, Dr. Khanna said. “The previous recommendation in 2013 was to consider FMT, but the body of research has grown to demonstrate its efficacy,” he said.

The guideline authors recommend that FMT be repeated for patients experiencing a recurrence of CDI within eight weeks of an initial FMT. In addition, for patients with recurrent CDI who are not candidates for FMT, have relapsed after FMT, or require ongoing or frequent courses of antibiotics, the guidelines suggest using long-term suppressive oral vancomycin.

For patients with a first recurrence of CDI, the guidelines suggest use of tapering or pulsed-dose vancomycin or fidaxomicin if patients were previously administered vancomycin or metronidazole.

The guidelines recommend testing only of patients with symptoms suggestive of active CDI and use of a highly sensitive and specific CDI testing algorithm to help distinguish between colonization and active infection.

According to the guidelines, severe CDI is diagnosed if the white blood cell count is 15,000 cells/mm3 or higher or serum creatinine is greater than 1.5 mg/dL, and fulminant CDI should be diagnosed if the patient has hypotension, shock, ileus or megacolon in the presence of typical CDI symptoms.

For patients with fulminant CDI, the guideline authors urge adequate volume resuscitation and oral vancomycin for the first 48 to 72 hours, with the possible addition of parenteral metronidazole, and use of vancomycin enemas for patients with an ileus.

The panel also recommends against discontinuing antisecretory therapy when it is indicated in patients with CDI. They also include a recommendation against the use of probiotics to prevent CDI or recurrent CDI.

There are several recommendations specifically targeted to the inflammatory bowel disease population, including CDI testing of IBD patients presenting with an acute flare and diarrhea. Other population-specific recommendations target patients who are pregnant, lactating or immunocompromised.

 

ACG 2021
Annual Scientific Meeting & Postgraduate Course

The Premier GI Clinical Meeting
& Postgraduate Course

October 22-27, 2021 • Mandalay Bay

 

Microbiota Restoration Therapy (MRT) (Drug Platform) Reduces Antibiotic-resistant Bacteria Gut Colonization In Patients with Recurrent C. difficile Infection (rCDI)

Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study

Abstract

Background

Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI.

Methods

An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N = 16) or two doses of RBX2660 (N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms.

Results

Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted.

Conclusions

Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others.

Trial registration

ClinicalTrials.gov, NCT01925417; registered on August 19, 2013.

 

To read the article in its entirety – please click on the following link to be redirected:

https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-021-00843-9#citeas

Seres Therapeutics and Nestle’ Health Science Team Up For the Joint Commercialization of Seres Therapeutics Investigational Microbiome Treatment for Recurrent C. difficile Infection (rCDI)

Seres Therapeutics and Nestlé Health Science have announced a decision to team up for the joint commercialization of Seres’s investigational oral microbiome treatment for recurrent Clostridioides difficile (C. difficile) infections (CDI).

Nestlé Health Science had previously received commercial rights to Seres’s therapeutics for inflammatory bowel disease and CDI, but only outside the U.S. and Canada. This expansion places Nestlé as Seres’s global collaborator for SER-109, a therapy the company hopes to treat a leading contributor to hospital-acquired infections in North America. If approved by the U.S. Food and Drug Administration (FDA), the agent, dubbed SER-109, will be the first microbiome therapeutic available.

Each year, CDI contributes to the deaths of 20,000 Americans. Standard of care for recurrent CDI includes the use of fecal microbial transplants. Currently, there is no microbiome therapies approved for any indications, which has created an unmet need recognized by an ever-growing list of pharmaceutical companies partnering with microbiome startups.

Seres’s investigational SER-109 includes purified Firmicutes spores; the rationale for including these spores is “based on their modulatory role in the life cycle of C. difficile and disease pathogenesis,” according to a statement made by the company.

Findings from the pivotal Phase III ECOSPOR III trial announced back in August 2020 showed SER-109 significantly reduced the CDI recurrence rate compared with placebo over an eight-week period. The absolute reduction of the CDI recurrence rate was 27% while the relative risk reduction was 68%. In addition, up to 88% of patients experienced a sustained clinical response by the end of the eight weeks.

Nestlé Health Science has agreed to use Aimmune Therapeutics, the company’s global pharmaceutical business, to lead the commercialization of the therapy. In return, Seres has agreed to receive upfront licensing payments totaling $175 million. An additional $125 million will be paid to Seres by Nestlé upon FDA approval of the microbiome agent.

Under terms of the agreement, Seres holds the sole responsibility for costs associated with development and pre-commercialization of SER-109 in the U.S. The company will be eligible to receive up to 50% of the commercial profits once the therapeutic is commercialized.

“Nestlé Health Science has been a terrific collaborator in our quest to develop a new treatment option for patients suffering from recurrent C. difficile infection, and their support over the past few years has been critical in advancing SER-109 to address this unmet need,” said Eric Shaff, Seres Therapeutics’ chief executive officer, in a statement. “As we prepare for potential approval and commercialization, we are eager to embark side-by-side on our next phase with a company that believes as fervently as we do in the potential of this transformative approach to reduce the recurrence of CDI.”

Nestlé Health Science’s CEO, Greg Behar, added that the company “is focused on the fast-developing areas of gut health, food allergies and metabolic health within our global pharmaceutical business, Aimmune Therapeutics.” As such, Aimmune’s “fully integrated commercial infrastructure” will be leveraged to launch the therapy, pending approval.

Seres has been busy this year in moving its investigational microbiome therapy pipeline in front of the FDA. Last month, Seres announced the agency had cleared an Investigational New Drug application for the company’s other investigational microbiome therapeutic for preventing antibiotic-resistant bacterial infections as well as graft-versus-host disease.

The company is advancing SER-155 into a Phase Ib trial under a collaboration with Memorial Sloan Kettering Cancer Center. “SER-155 represents a novel microbiome technology with the potential to address antibiotic-resistant bacterial bloodstream infections and further to modulate host immunomodulatory responses to decrease graft-versus-host disease,” said Seres’s chief scientific officer, Matthew Henn, Ph.D., in a statement.

 

SOURCE:  https://www.biospace.com/article/seres-nestle-agree-to-jointly-commercialize-microbiome-agent-for-c-diff-infections/

IDSA, SHEA Update ADULT C. difficile Infection (CDI) Treatment Guidelines

“The panel’s recommendations for the management of CDI are based upon evidence derived from topic-specific systematic literature reviews,” Stuart Johnson, MD, infectious disease clinician and researcher at the Edward Hines Jr. Veterans Administration Hospital, and colleagues wrote.

The new guidance for CDI management in adults is as follows:

  • For patients with an initial C. difficile episode, fidaxomicin is recommended rather than a standard course of vancomycin.
  • For patients with recurrent C. difficile episodes, a standard or extended-pulsed regimen of fidaxomicin should be used rather than a standard course of vancomycin.
  • For patients with a recurrent C. difficile episode within the past 6 months, bezlotoxumab and standard-of-care antibiotics should be used rather than standard-of-care antibiotics alone.

“Head-to-head trials of differing anti-CDI recurrence strategies using narrow-spectrum antibiotics that target C. difficile, restoration of the microbiome using biotherapeutics or [fecal microbiota transplantation], or augmentation of the host immune response with agents such as bezlotoxumab given alone or in combination (eg, in combination with fidaxomicin) are needed,” the authors wrote.

 

SOURCE:  https://www.healio.com/news/infectious-disease/20210624/idsa-shea-update-guidance-for-managing-patients-with-c-difficile

C. diff. Spores and More Live Broadcast Enters Season VI

Welcome to Season VI on 

C. diff. Spores and More

Live Broadcast, sponsored

by Clorox Healthcare.

 

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

Do you have a specific topic of interest or would like to learn more about a specific product or procedure?  Send an email to info@cdifffoundation.org and share your suggestions and interests.

“None of us can do this alone ~ All of us can do this together.”

Join us every Tuesday at 1:00 p.m. EST for the Live Broadcast  www.cdiffradio.com