Category Archives: Clostridioides difficile Infection

JAMA: Prevalence of Detection of CDI (C. difficile) Among Asymptomatic Children, A Systematic Review and Meta-analysis

 

 

 

Sarah R. Tougas, BScN, MD1Nidhi Lodha, MBBS, MSc1Ben Vandermeer, PhD2et alDiane L. Lorenzetti, PhD3Phillip I. Tarr, MD4,5Gillian A. M. Tarr, PhD6Linda Chui, PhD7Otto G. Vanderkooi, MD8,9Stephen B. Freedman, MDCM, MSc10,11

JAMA Pediatr. Published online August 2, 2021. doi:10.1001/jamapediatrics.2021.2328

 

Question  What is the prevalence of Clostridioides difficile detection among asymptomatic children across the age spectrum?

Findings  In this systemic review and meta-analysis of 95 studies with 19 186 participants, the prevalence of detection of toxigenic and nontoxigenic C difficile was greatest (41%) among infants aged 6 to 12 months and was lowest (12%) among children aged 5 to 18 years. The prevalence of toxigenic C difficile detection was greatest (14%) among infants aged 6 to 12 months.

Meaning  These findings suggest that test result interpretation should include consideration of the high likelihood of C difficile colonization in young children.

Abstract

Importance  Detection of Clostridioides difficile has frequently been described in asymptomatic infants and children, but accurate estimates across the age spectrum are unavailable.

Objective  To assess the prevalence of C difficile detection among asymptomatic children across the age spectrum.

Data Sources  This systematic review and meta-analysis included a search of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, Scopus, and Web of Science for articles published from January 1, 1990, to December 31, 2020. Search terms included Clostridium difficilePeptoclostridium difficileClostridioides difficileCDF OR CDI OR c diff OR c difficileClostridium infections OR cd positive diarrhea OR cd positive diarrhea OR Clostridium difficile OR Peptoclostridium difficile OR pseudomembranous colitis OR pseudomembranous enterocolitisenterocolitis, and pseudomembranous. These were combined with the following terms: bacterial colonization and colonization OR colonized OR colonizing OR epidemiology OR prevalence OR seroprevalence.

Study Selection  Studies were screened independently by 2 authors. Studies were included if they reported testing for C difficile among asymptomatic children (ie, children without diarrhea) younger than 18 years.

Data Extraction and Synthesis  Data were extracted independently and in duplicate by 2 reviewers. Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) guidelines were used. Data were pooled using a random-effects model.

Main Outcomes and Measures  The primary outcome was prevalence of C difficile detection among asymptomatic children. Secondary outcomes included prevalence of toxigenic vs nontoxigenic strains of C difficile and prevalence of C difficile detection stratified by geographic region, income status, testing method, and year of testing.

Results  A total of 95 studies with 19 186 participants were included. Rates of detection of toxigenic or nontoxigenic C difficile were greatest among infants aged 6 to 12 months (41%; 95% CI, 32%-50%) and decreased to 12% (95% CI, 7%-18%) among children aged 5 to 18 years. The prevalence of toxigenic C difficile colonization was lower, peaking at 14% (95% CI, 8%-21%) among infants aged 6 to 12 months and decreasing to 6% (95% CI, 2%-11%) among children older than 5 years. Although prevalence differed by geographic region (ie, North and South America vs Europe: β, −0.151, P = .001; North and South America vs Western Pacific: β, 0.136, P = .007), there was no difference by testing method (ie, culture vs polymerase chain reaction: β, 0.069, P = .052; culture vs enzyme immunoassay: β, −0.178, P = .051), income class (low-middle income vs high income: β, −0.144, P = .23; upper-middle vs high income: β, −0.020, P = .64), or period (before 1990 vs 2010-2020: β, −0.125, P = .19; 1990-1999 vs 2010-2020: β, −0.037, P = .42; 2000-2009 vs 2010-2020: β, −0.006, P = .86).

Conclusions and Relevance  In this systematic review and meta-analysis, C difficile colonization rates among children were greatest at 6 to 12 months of age and decreased thereafter. These estimates may provide context for interpreting C difficile test results among young children.

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https://jamanetwork.com/journals/jamapediatrics/article-abstract/2782616

Contagion Live Presents: Where Are We With Clostridioides Difficile?

MEDIA PARTNER

In this episode, our 1 Big Question is: Looking at C diff as a whole, would you say the medical community is doing a better job overall of treatment and what challenges remain?

We interviewed Sahil Khanna, MBBS, MS, who is professor of Medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic; Glenn Tillotson, PhD, FIDSA, FCCP, GST Micro LLC; Payal K. Patel, MD, MPH, Division of Infectious Diseases

assistant professor, University of Michigan Health System and medical director of Antimicrobial Stewardship, VA Ann Arbor; and Anurag Malani, MD, infectious diseases specialist, St. Joseph Hospital, and a fellow of Infectious Diseases Society of America (IDSA).

https://www.contagionlive.com/view/where-are-we-with-clostridioides-difficile-

Dale Gerding, MD, FACP, FIDSA, FSHEA To Chair the July 16, 2021 C. diff. Patient, Family, and Caregiver Live-Online Symposium

Scientific Advisor Prof Dale Gerding to chair C. diff. Foundation

C. diff. Patient, Family, and Caregiver Symposium

July 16th  – Live-Online beginning at 1:00 p.m. – 3:00 p.m. EDT 

Register Today!

 

 

 

 

Brighton, United Kingdom – 02 July 2021 – Destiny Pharma plc (AIM: DEST), a clinical stage innovative biotechnology company focused on the development of novel medicines to prevent life-threatening infections, is pleased to announce that its Scientific Advisory Board member, Professor Dale Gerding, a world-leading expert in C. difficile infections (CDI) and the discoverer of NTCD-M3, will be chairing the “C. diff. Patient, Family, and Caregiver” Symposium, to be held virtually on 16 July 2021.

The Symposium, hosted by the C Diff Foundation, will be a gathering of healthcare professionals, practitioners, thought leaders, and C. diff. survivors focused on transforming the patient experience of people living with C. diff. infections worldwide.

Distinguished members and keynote speakers will provide insight on how to identify, evaluate, and prioritize innovations that can quickly touch the lives of patients battling C. diff. infections.

Destiny Pharma’s late-stage asset, NTCD-M3, is a novel microbiome therapeutic being developed to reduce the recurrence of C. diff. infections in the gut. CDI is the leading cause of hospital acquired infection in the US and current treatments lead to significant recurrence. In the US, there are approximately 500,000 cases of CDI each year; many of these initial cases then recur leading to 29,000 deaths per year.

NTCD-M3 has the potential to become the leading treatment for CDI, as it has shown to deliver clear advantages to both existing CDI treatment options and also to those currently in clinical development.

About Destiny Pharma plc
Destiny Pharma is a UK based, clinical stage, innovative biotechnology company focused on the development of novel medicines that can prevent life-threatening infections. Its pipeline has novel microbiome-based biotherapeutics and XF drug clinical assets including NTCD-M3, a Phase 3 ready treatment for the prevention of C. difficile infection (CDI) recurrence, which is the leading cause of hospital acquired infection in the US and also XF-73 nasal gel, which has recently completed a positive Phase 2b clinical trial targeting the prevention of post-surgical staphylococcal hospital infections including MRSA. It is also co-developing SPOR-COV, a novel, biotherapeutic product for the prevention of COVID-19 and other viral respiratory infections, and has earlier grant funded XF research projects. 

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.

 

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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/