Author Archives: cdifffoundation

Review Article: The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection: Current Understanding and Gap Analysis

The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection: Current Understanding and Gap Analysis

Mark H. Wilcox,1,2 Barbara H. McGovern,3, and Gail A. Hecht4,5

1 Department of Microbiology, Old Medical School, Leeds Teaching Hospitals NHS Trust, Leeds, UK, 2 University of Leeds, Leeds, UK, 3 Seres Therapeutics, Medical Affairs, Cambridge, Massachusetts, USA, 4 Department of Medicine, Division of Gastroenterology, Loyola University Chicago, Chicago, Illinois, USA, and 5 Department of Microbiology and Immunology, Loyola University Chicago, Chicago, Illinois, USA The leading risk factor for Clostridioides

Abstract: The leading risk factor for Clostridioides (Clostridium) difficile infection (CDI) is broad-spectrum antibiotics, which lead to low microbial diversity, or dysbiosis. Current therapeutic strategies for CDI are insufficient, as they do not address the key role of the microbiome in preventing C. difficile spore germination into toxin-producing vegetative bacteria, which leads to symptomatic disease. Fecal microbiota transplant (FMT) appears to reduce the risk of recurrent CDI through microbiome restoration. However, a wide range of efficacy rates have been reported, and few placebo-controlled trials have been conducted, limiting our understanding of FMT efficacy and safety. We discuss the current knowledge gaps driven by questions around the quality and consistency of clinical trial results, patient selection, diagnostic methodologies, use of suppressive antibiotic therapy, and methods for adverse event reporting. We provide specific recommendations for future trial designs of FMT to provide improved quality of the clinical evidence to better inform treatment guidelines.

 

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https://www.scilit.net/article/7444c3597a3c208e70317498502f6beb

Major Article: SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial

SER-109, an Investigational Microbiome Drug to Reduce
Recurrence After Clostridioides difficile Infection: Lessons
Learned From a Phase 2 Trial.

Barbara H. McGovern,1,a,  Christopher B. Ford,1,a , Matthew R. Henn,1,a , Darrell S. Pardi 2
Sahil Khanna,2  Elizabeth L. Hohmann,3  Edward J. O’Brien,1
Christopher A. Desjardins,1, Patricia Bernardo,1, Jennifer R. Wortman,1, Mary-Jane Lombardo,1
Kevin D. Litcofsky,1, Jonathan A. Winkler,1, Christopher W. J. McChalicher,1, Sunny S. Li,1,
Amelia D. Tomlinson,1,Madhumitha Nandakumar,1 David N. Cook1,
Roger J. Pomerantz,1, John G. Auninš,1, and Michele Trucksis1,

1 Seres Therapeutics, Cambridge, Massachusetts, USA, 2 Mayo Clinic, Gastroenterology Division, Rochester, Minnesota, USA, and 3 Massachusetts General Hospital, Infectious Diseases Division, Boston, Massachusetts, USA

Background. Recurrent Clostridioides difficile infection (rCDI) is associated with loss of microbial diversity and microbe-derived secondary bile acids, which inhibit C. difficile germination and growth. SER-109, an investigational microbiome drug of donor-derived, purified spores, reduced recurrence in a dose-ranging, phase (P) 1 study in subjects with multiple rCDIs.

Methods. In a P2 double-blind trial, subjects with clinical resolution on standard-of-care antibiotics were stratified by age (< or ≥65 years) and randomized 2:1 to single-dose SER-109 or placebo. Subjects were diagnosed at study entry by PCR or toxin testing.

Safety, C. difficile–positive diarrhea through week 8, SER-109 engraftment, and bile acid changes were assessed.

Results. 89 subjects enrolled (67% female; 80.9% diagnosed by PCR). rCDI rates were lower in the SER-109 arm than placebo
(44.1% vs 53.3%) but did not meet statistical significance. In a preplanned analysis, rates were reduced among subjects ≥65 years
(45.2% vs 80%, respectively; RR, 1.77; 95% CI, 1.11–2.81), while the <65 group showed no benefit. Early engraftment of SER-109
was associated with nonrecurrence (P < .05) and increased secondary bile acid concentrations (P < .0001). Whole-metagenomic sequencing from this study and the P1 study revealed previously unappreciated dose-dependent engraftment kinetics and confirmed
an association between early engraftment and nonrecurrence. Engraftment kinetics suggest that P2 dosing was suboptimal.

Adverse events were generally mild to moderate in severity.

Conclusions. Early SER-109 engraftment was associated with reduced CDI recurrence and favorable safety was observed. A higher dose of SER-109 and requirements for toxin testing were implemented in the current P3 trial. Clinical Trials Registration. NCT02437487, https://clinicaltrials.gov/ct2/show/NCT02437487?term=SER-109&draw=2&rank=4.

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The 4th Annual Global C. diff. Awareness 2K Walks Go Virtual on September 11 and 12

The 4th Annual Global C.diff. Awareness 2K Walks Will Now Be VIRTUAL!

                   Join Us On……………….

Friday, September 11th – UK

Dr. Clokie, UK Walk Event Coordinator, will be hosting the VIRTUAL Walk in Leicester on September 11th as the UK is also under strict guidelines to slow the spread of the COVID-19 virus. 

  • The Leicester VIRTUAL Walk Will Begin at 10:00 a.m. – 11:00 a.m. – UK

  • VIRTUAL Entertainment Will Begin at 10:00 a.m. UK For the Children!

Saturday, September 12th –  USA

  • The VIRTUAL Walks Will Begin at 9:00 a.m. through 12:00 p.m. EDT

  • VIRTUAL Entertainment Will Begin at 9:00 a.m. EDT For the Children!

All Registered Awareness Walkers Will Receive a T-Shirt, Giveaways, and More via: United States Postal Service To the Address Provided at the Time Of Registration.

To Learn More About the Global C. diff. Awareness Walk Event and How You Can Register, Please Click On the Green Button Below……………..

 

 

 

We are truly grateful for your efforts, support and participation
of the Annual Walk events and we look forward to virtually walking with you in September!

“None of us can do this alone ~ All of us can do this together!”
~ C Diff Foundation

World Microbiome Day 2020 Information

Microbiome research impacts many facets of life on Earth (and beyond).
In a dedicated page for World Microbiome Day 2020, MicrobiomeAnimal Microbiome and Environmental Microbiome have highlighted some of the many ways microbiome research has benefited us.

 

 

 

Click on the graphic above to access the World Microbiome 2020 Page

World Microbiome Day was founded by APC Microbiome Ireland in 2019. It aims to celebrate all things microbe and to raise awareness of the diverse world of microbiomes and their impact on human, animal, and environmental health.

In honour of the World Microbiome Day 2020  day, the BMC is proud to present this collection of microbiome research specially selected by our editors.

The BMC (Biomed Central) Research In Progress — A pioneer of open access publishing, BMC has an evolving portfolio of high quality peer-reviewed journals including broad interest titles such as BMC Biology and BMC Medicine, specialist journals such as Malaria Journal and Microbiome, and the BMC Series.

https://www.biomedcentral.com/

Expanding beyond biomedicine into the physical sciences, mathematics and engineering disciplines, BMC now offers a wider portfolio of subject fields on a single open access platform.

At BMC, research is always in progress. We are committed to continual innovation to better support the needs of our communities, ensuring the integrity of the research we publish, and championing the benefits of open research. BMC is part of Springer Nature.

BMC has an evolving portfolio of some 300 peer-reviewed journals, sharing discoveries from research communities in science, technology, engineering and medicine. In 1999 we made high quality research open to everyone who needed to access it – and in making the open access model sustainable, we changed the world of academic publishing.

 

For Patients Confirmed With COVID-19 – U.S. Food and Drug Administration (FDA) Has Issued an Emergency Use Authorization (EUA) for the Elecsys® IL-6 Test

Roche’s Elecsys IL-6 test receives FDA Emergency Use Authorization to help in identifying patients at high risk of severe inflammatory response

  • FDA EUA1 now makes IL-6 testing accessible to patients in the United States to assist in identifying severe inflammatory response in patients with confirmed COVID-19 and is also available in markets accepting the CE-mark2
  • Interleukin 6 (IL-6) is an early indicator for acute inflammation to aid in the management of critically ill patients
  • This test is available on Roche’s cobas e analysers which are widely available around the world

 
Roche announced on June 4, 2020 that the U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the Elecsys® IL-6 test. This test measures levels of the biomarker interleukin 6 (IL-6) and can be used to help identify patients with confirmed COVID-19 disease who could be at high risk of intubation with mechanical ventilation.

The test can support physicians, in combination with other examinations and vital signs, to decide early on if a patient with confirmed COVID-19 illness requires mechanical ventilation.“The FDA EUA approval of Elecsys IL-6 is another step in our commitment to deliver fast and reliable diagnostic tests to help fight the coronavirus pandemic,” said Thomas Schinecker, CEO Roche Diagnostics. “In the current situation, time is specifically critical. The test could help physicians in the quick identification of severe inflammatory response in patients infected with the SARS CoV-2 virus.”

“In the current pandemic, Roche’s Elecsys IL-6 test was helpful as an early indicator for acute inflammation and in the management of critically ill patients,” said Tobias Herold, MD from the Emergency Department, University Hospital, LMU University Munich, Germany. “Elevated IL-6 values help us to identify patients with a high risk of upcoming respiratory failure.

Hospitals and reference laboratories can run the Elecsys IL-6 test on Roche’s cobas e® analysers which are widely available around the world. These fully-automated systems can provide test results in approximately 18 minutes, with a test throughput of up to 300 tests/hour, depending on the analyser.

About Elecsys IL-6
The IL-6 immunoassay is an in vitro diagnostic test for the quantitative determination of IL-6 (interleukin-6) in human serum or plasma. This assay is used in countries accepting CE-mark to aid in the management of critically ill patients, as an early indicator for acute inflammation. Under the Emergency Use Authorization in the US, this assay can be used to assist in identifying severe inflammatory response in patients with confirmed COVID‑19 illness to aid in determining the risk of intubation with mechanical ventilation, in conjunction with clinical findings and the results of other laboratory testing. IL-6 is released by immune cells, once they are activated by virus, bacteria or other immune cells. IL-6 acts like a messenger to activate other immune cells to fight the infection. Because IL-6 is released so early during a severe infection, it helps physicians to identify severely ill COVID-19 patients as early as possible. Hospitals and reference laboratories can run the test on Roche’s cobas e analysers which are widely available around the world. These fully-automated systems can provide test results in approximately 18 minutes, with a test throughput of up to 300 tests/hour, depending on the analyser.

About Roche’s response to the COVID-19 pandemic
The COVID-19 pandemic continues to evolve globally with varying developments from country to country and we are partnering with healthcare providers, laboratories, authorities and organisations to help make sure that patients receive the tests, treatment and care they need.

Reliable, high-quality testing is essential to help healthcare systems overcome this pandemic. On 13 March we received FDA Emergency Use Authorization for a high-volume molecular test to detect SARS-CoV-2, the virus that causes COVID-19, which is also available in countries accepting the CE Mark. On 3 May, Roche announced that its COVID-19 antibody test, aimed at detecting the presence of antibodies in the blood, also received FDA Emergency Use Authorization and is available in markets accepting the CE mark. Our existing diagnostics portfolio for critical care has also been playing a significant role in supporting patient management during the COVID-19 crisis, with our blood gas and sepsis products being used to monitor patients in the acute setting. Roche is working closely with governments and health authorities around the world, and has significantly increased production to help ensure availability of tests globally.

While there are currently no approved medicines for the treatment of patients with COVID-19, we are actively involved in understanding the potential of our existing portfolio and are researching options for the future. On 19 March, we announced the initiation of COVACTA – a global Phase III randomised, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of intravenous Actemra©/RoActemra© (tocilizumab) plus standard of care in hospitalised adult patients with severe COVID-19 pneumonia compared to placebo plus standard of care. Roche has also initiated an internal early research programme focused on the development of medicines for COVID-19 and is evaluating a large number of potential collaborations.

In these exceptional times, Roche stands together with governments, healthcare providers and all those working to overcome the pandemic.

About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the eleventh consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2019 employed about 98,000 people worldwide. In 2019, Roche invested CHF 11.7 billion in R&D and posted sales of CHF 61.5 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References
[1] The Emergency Use Authorization (EUA) authority allows FDA to help strengthen the nation’s public health protections against CBRN threats by facilitating the availability and use of medical countermeasures needed during public health emergencies https://www.fda.gov/home
[2] CE-IVD marking is granted through completion of a comprehensive technical validation and self declaration under the European Directive for In Vitro Diagnostic Medical Devices.