Category Archives: C. diff. Research Community

In-Home Enrollment Of Randomized Controlled Trials Finds To Be An Innovative Method Improving Access To Clinical Research

Abstract

Introduction: Clostridioides difficile infection is the leading cause of infectious diarrhea in the United States, with substantial morbidity and mortality. Recurrent infection is especially challenging, with each recurrence increasing the likelihood of a successive recurrence, leading to cycles of prolonged symptoms, frequent antimicrobial use, and decreased quality of life. Fecal microbiota transplantation to prevent recurrent infection is a promising intervention with a large effect size in observational studies, but with conflicting results from randomized controlled trials. We are conducting a Veterans Affairs-wide randomized controlled trial utilizing centralized case identification, with enrollment and fecal microbiota transplant administration occurring at the participant’s home. This type of trial design significantly improves trial efficiency, greatly decreases trial cost, increases consistency of trial administration, and most importantly makes nationwide clinical trials in less-common diseases possible.

Methods: This is a randomized comparison of capsule-delivered fecal microbiota transplant for the prevention of recurrent Clostridioides difficile infection, administered after successful initial treatment of recurrent C. difficile infection with standard therapy. The primary endpoint is the incidence of recurrent C. difficile infection or death. Cases are identified by searching the Veterans Affairs Corporate Data Warehouse, with central study coordinators then reaching out to potential participants. Individuals meeting inclusion criteria and interested in participation are scheduled for in-home consent, randomization, and capsule administration, followed by telephone follow-up for 6 months. To mitigate risks of COVID-19, enrollment via video visits has been implemented.

Results: A total of 102 participants have been enrolled through January 2021. Centralized case identification and in-home enrollment has facilitated enrollment from 34 unique states, with 38% being from rural or highly rural areas.

Discussion: Centralized case identification and in-home enrollment is a feasible and innovative method of conducting randomized controlled trials in the Veterans Affairs system, improving access to clinical research for populations who may have difficulty engaging with the traditional model of clinical trials where enrollment is based at large hospitals in major metropolitan areas.

Keywords: Fecal microbiota transplant; centralized enrollment; Clostridioides difficile; diarrhea; randomization; recurrence; stool transplant.

source:  https://pubmed.ncbi.nlm.nih.gov/34154439/

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/

Bloody Diarrhea Is a Common Condition In Dogs, But Studies Evaluating the Enteropathogens Involved

Enteric organisms detected in feces of dogs with bloody diarrhea: 45 cases

Carolina Pantuzza Ramos 1Amanda Nádia Diniz 1Marcio Garcia Ribeiro 2Carolina Lechinski de Paula 2Érica Azevedo Costa 1Luciana Sonne 3Silvia Trindade Pereira 4Carlos Eduardo Bastos Lopes 1Mário Cesar Rennó 5Rodrigo Otávio Silveira Silva 6

  • PMID: 34044173
  • DOI: 10.1016/j.tcam.2021.100549

Abstract

Bloody diarrhea is a common condition in dogs, but studies evaluating the enteropathogens involved specifically in adult dogs are scarce.

In the present study, stool samples from 45 adult dogs with bloody diarrhea were evaluated for the four enteric organisms mainly reported in these cases: canine parvovirus type 2 (CPV-2), Clostridioides difficile, Clostridium perfringens, and Salmonella spp.

In addition, the samples were also tested for coronavirus, rotavirus, Giardia spp., and Escherichia coli pathotypes to provide a better understanding of possible co-occurrence. Vaccination status, diet, and clinical outcome were also obtained when available. CPV-2b was identified in 17 dogs (37.8%), being the most frequent cause of bloody diarrhea, including completely vaccinated adult dogs. Toxigenic C. difficile and C. perfringens netF+ were detected in six (13.3%) and five (11.1%) dogs, in some cases in co-occurrence with other enteric organisms. Three fatal cases of salmonellosis were identified in dogs fed a raw meat-based diet, raising the risks associated with this increasing practice.

To read this study in its entirety, please click on the link below:

https://pubmed.ncbi.nlm.nih.gov/34044173/

Researchers Conduct Study To Establish a Quantitative Correlation Between Applied Alcohol-Based Hand Rub ABHR Volume and Achieved Hand Coverage Utilizing an Innovate Quantitative Evaluation System

A large-scale investigation of alcohol-based hand rub (ABHR) volume: hand coverage correlations utilizing an innovative quantitative evaluation system

  • Constantinos Voniatis,
  • Száva Bánsághi,
  • Andrea Ferencz &
  • Tamás Haidegger

 

Abstract

Background

Current hand hygiene guidelines do not provide recommendations on a specific volume for the clinical hand rubbing procedure. According to recent studies volume should be adjusted in order to achieve complete coverage. However, hand size is a parameter that highly influences the hand coverage quality when using alcohol-based hand rubs (ABHR). The purpose of this study was to establish a quantitative correlation between applied ABHR volume and achieved hand coverage.

Method

ABHR based hand hygiene events were evaluated utilizing a digital health device, the Semmelweis hand hygiene system with respect to coverage achieved on the skin surface. Medical students and surgical residents (N = 356) were randomly selected and given predetermined ABHR volumes. Additionally, hand sizes were calculated using specialized software developed for this purpose. Drying time, ABHR volume awareness, as well spillage awareness were documented for each hand hygiene event.

Results

Hand coverage achieved during a hand hygiene event strongly depends on the applied ABHR volume. At a 1 ml dose, the uncovered hand area was approximately 7.10%, at 2 ml it decreased to 1.68%, and at 3 ml it further decreased to 1.02%. The achieved coverage is strongly correlated to hand size, nevertheless, a 3 ml applied volume proved sufficient for most hand hygiene events (84%). When applying a lower amount of ABHR (1.5 ml), even people with smaller hands failed to cover their entire hand surface. Furthermore, a 3 ml volume requires more than the guideline prescribed 20–30 s to dry. In addition, results suggest that drying time is not only affected by hand size but perhaps other factors may be involved as well (e.g., skin temperature and degree of hydration). ABHR volumes of 3.5 ml or more were inefficient, as the disinfectant spilled while the additional rubbing time did not improve hand coverage.

Conclusions

Hand sizes differ a lot among HCWs. After objectively measuring participants, the surface of the smallest hand was just over half compared to the largest hand (259 cm2 and 498 cm2, respectively). While a 3 ml ABHR volume is reasonable for medium-size hands, the need for an optimized volume of hand rub for each individual is critical, as it offers several advantages. Not only it can ensure adequate hand hygiene quality, but also prevent unnecessary costs. Bluntly increasing the volume also increases spillage and therefore waste of disinfectant in the case of smaller hands. In addition, adherence could potentially decrease due to the required longer drying time, therefore, adjusting the dosage according to hand size may also increase the overall hand hygiene compliance.

To read this Abstract in its entirety please click on the link below to be redirected. Thank you.

https://aricjournal.biomedcentral.com/articles/10.1186/s13756-021-00917-8/

Clostridioides diffiicle Thrives In an Inflammed Environement ….Research Study From North Carolina State University

Clostridioides difficile thrives in an inflamed environment by generating toxins that support prolonged infection, according to a study from North Carolina State University.

The study, published in Nature Communications, showed how C. diff produces toxins that cause inflammation, eliminating competing bacteria and releasing peptides and amino acids that support the growth of C. diff.

C. diff thrives when other microbes in the gut are absent – which is why it is more prevalent following antibiotic therapy,” corresponding author Casey Theriot, Ph.D., associate professor of infectious disease at North Carolina State University, said. “But when colonizing the gut,
C. diff. also produces two large toxins, TcdA and TcdB, which cause inflammation. We wanted to know if these inflammation-causing toxins actually give C. diff a survival benefit – whether the pathogen can exploit an inflamed environment in order to thrive.”

Investigators examined two variants of C. diff in vitro and in an antibiotic-treated mouse model. The variants included a wild type C. diff that produces toxins and a genetically modified variant that does not. They found that the wild type C. diff, associated with toxin production, generated more inflammation and tissue damage than the mutant.

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

https://www.contagionlive.com/view/clostridioides-difficile-thrives-in-inflamed-environment

Investigators also found changes in the expression of metabolic genes, with C. diff in the inflamed environment expressing more genes related to carbohydrate and amino acid metabolism that sustains growth.

C. diff’s toxins damage the cells that line the gut,” Theriot said. “These cells contain collagen, which is made up of amino acids and peptides. When collagen is degraded by toxins,
C. diff responds by turning on expression of genes that can use these amino acids for growth.”

Inflammation provided a second benefit to C. diff by creating an inhospitable environment for other bacteria that compete for nutrients. Bacteroidaceae were present in control groups that weren’t infected with toxin-producing C. diff, which was consistent with previous studies that found negative associations between C. diff and Bacteroidaceae.

“I always found it interesting that C. diff causes such intense inflammation,” first author Josh Fletcher, Ph.D., a former postdoctoral researcher at North Carolina State University, said. “Our research shows that this inflammation may contribute to the persistence of C. diff in the gut environment, prolonging infection.”

C. diff is the most significant cause of hospital-acquired diarrhea, causing more than 223,900 infections and 12,800 deaths in the US in 2017, according to a recent report.

The disease has two phases, a spore phase, and vegetative phase. Toxins are released during the vegetative phase, causing diarrhea and other symptoms. But the pathogen is often transmitted during the spore phase, during which it is hardy and isn’t susceptible to gastric acids and alcohol-based hand sanitizer, experts explained during a recent discussion of the disease.

Risks for infection include exposure to C. diff spores and antibiotic use. An investigational drug to prevent the disruption of the gut microbiota by antibiotics is among the most recent developments in the fight against a C diff. infection.