Tag Archives: Clostridioides difficile Research and Development

The Food and Drug Administration (FDA) Informs Health Care Providers and Patients of the Potential Risk of Transmission of SARS-CoV-2 Virus and COVID-19 By the Use of Fecal Microbiota for Transplantation (FMT)

The global public health community is responding to a rapidly evolving pandemic of respiratory disease caused by a novel coronavirus that was first detected in China.

 

The virus has been named “SARS-CoV-2” and the disease it causes has been named “COVID-19.”

The Food and Drug Administration (FDA) is informing health care providers and patients of the potential risk of transmission of SARS-CoV-2 virus by the use of fecal microbiota for transplantation (FMT) and that FDA has determined that additional safety protections are needed.

Summary of the Issue

Several recent studies have documented the presence of SARS-CoV-2 ribonucleic acid (RNA) and/or SARS-CoV-2 virus in stool of infected individuals.1,2,3 This information suggests that SARS-CoV-2 may be transmitted by FMT, although the risk of such transmission is unknown.4 At this time, testing nasopharyngeal specimens from stool donors for SARS-CoV-2 may not be widely available. Furthermore, there is limited information on the availability and sensitivity of direct testing of stool for SARS-CoV-2.

Additional Protections for the Use of FMT

At this time, FDA is advising that clinical use of FMT has the potential to transmit SARS-CoV-2, whether used as part of a study under an Investigational New Drug Application (IND) on file with the FDA or under FDA’s enforcement discretion policy. To address the risk, stool used for FMT should have been donated before December 1, 2019. Due to the potential for serious adverse events to occur, FDA has determined that the following protections are needed for any use of FMT that is found to be necessary for clincal care if it involves stool donated after December 1, 2019:

  • Donor screening with questions directed at identifying donors who may be currently or recently infected with SARS-CoV-2;
  • Testing donors and/or donor stool for SARS-CoV-2, as feasible;
  • Development of criteria for exclusion of donors and donor stool based on screening and testing; and
  • Informed consent that includes information about the potential for transmission of SARS-CoV-2 via FMT, including FMT prepared from stool from donors who are asymptomatic for COVID-19.

Actions

FDA is in the process of notifying IND holders of the potential risk of transmission of SARS-CoV-2 via FMT and of FDA’s determination that additional safety protections that are needed.

FDA is communicating this information with this statement to all other stakeholders to ensure that everyone is fully informed.

As the scientific community learns more about SARS-CoV-2 and COVID-19, FDA will provide further information as warranted.

Information for Health Care Providers and Patients on Enforcement Discretion

In July 2013, FDA issued a guidance document stating that it intends to exercise enforcement discretion under limited conditions regarding the IND requirements for the use of FMT products to treat C. difficile infection in patients that have not responded to standard therapies. The guidance states that FDA intends to exercise enforcement discretion provided that the treating physician obtains adequate consent for the use of FMT from the patient or his or her legally authorized representative. The consent should include, at a minimum, a statement that the use of FMT to treat C. difficile is investigational and a discussion of its potential risks.

Reporting Adverse Events

FDA encourages all health care providers and patients to report any suspected adverse events or side effects related to the administration of FMT products to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.

 


1 Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H, Evidence for gastrointestinal infection of SARS-CoV-2, Gastroenterology (2020), doi: https://doi.org/10.1053/j.gastro.2020.02.055External Link Disclaimer
2 Tang A, Tong Z-d, Wang H-l, Dai Y-x, Li K-f, Liu J-n, et al. Detection of novel coronavirus by RT-PCR in stool specimen from asymptomatic child, China. Emerg Infect Dis. (2020), https://doi.org/10.3201/eid2606.200301External Link Disclaimer from https://wwwnc.cdc.gov/eid/article/26/6/20-0301_article
3 Wang, W, Xu, Y, Gao, R, et al., Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA (2020), https://doi.org/10.1001/jama.2020.3786External Link Disclaimer
4 Gu J, Han B, Wang J, COVID-19: Gastrointestinal manifestations and potential fecal-oral transmission, Gastroenterology (2020), doi: https://doi.org/10.1053/j.gastro.2020.02.054

C Diff Foundation with Leading Gastroenterologist’s Oneto and Feuerstadt Announce November Clinic Dedicated for C.difficile

C Diff Foundation ( https://cdifffoundation.org/)  is a one hundred percent volunteer, world-renowned 501(c)(3) not-for-profit organization and has announced that the Foundation will offer a November clinic sponsored by the C Diff Foundation and dedicated to patients diagnosed and recovering from a C. difficile infection (CDI).

The November 19th C Diff Foundation Clinic will be hosted by Concorde Gastroenterology at their  233 Broadway Suite 840,  New York, NY 10279 office.
The clinic will hold office hours from 10:00 a.m. until  4:00 p.m. ET
With Doctor’s Caterina Oneto, MD and  Paul Feuerstadt, MD

Please call +1 212 889 5544 Ext 199
To schedule an appointment.

The August clinic received an overwhelming response from patients in various stages of recovery, including 15 individuals already scheduled with multiple spots planned for patients with recently diagnosed infection or those who have had multiple episodes and need further guidance and management.

Dr. Oneto said, “Through this clinic, we will provide access to high-level care to a number of new consults, as well as existing patients, who are recovering from the infection. It is my pleasure to partner with the C Diff Foundation and lend my expertise to the management and hopefully, eradication of this debilitating disease.”

“We are delighted with the immediate and overwhelming response from the patient community. It is a testament to the needs of those suffering from this infection. With this clinic, we hope to bring awareness, education and more importantly, cutting edge treatment to the general public,” stated Dr. Feuerstadt.

There are plans for additional clinic dates in 2020  in Florida, New York, Connecticut, Illinois, and Minnesota.

“The clinics demonstrate Doctor Oneto and Feuerstadt’s commitment over the years raising
C. diff. awareness while providing management of those suffering with
a C. diff. infection. Patients who might not otherwise be able to gain access to providers sub-specializing and caring for those with this infection will have this opportunity available.  Doctor’s Oneto and Feuerstadt’s dedication resonates within the C. diff. community and we are grateful for their participation and support.” stated Nancy Caralla, Founding President and Executive Director of the C Diff Foundation.

About C Diff Foundation

C Diff Foundation’s mission is dedicated to reaching out to communities from villages to cities, to medical practitioners, medical students, C. diff. survivors, caregivers, and the patients combating a C. difficile infection (CDI) while providing the general public important information on prevention, treatments available, clinical trials in progress, nutrition, diagnostics, and EPA registered products available for environmental safety worldwide.

About Caterina Oneto, MD

Dr. Caterina Oneto, MD is a Gastroenterologist in private practice in New York and is affiliated with NYU Langone. She completed her Fellowship in Gastroenterology at Montefiore Medical Center, Albert Einstein College of Medicine. Dr. Oneto is the Co-Director of Clinical trials at Concorde Medical Group. Her main focus is Irritable Bowel Disease (IBD),

About Paul Feuerstadt, MD

His areas of interest Clostridioides difficile infection (CDI) and ischemic diseases of the gut and in these areas he has presented his research extensively, authored and co-authored many manuscripts, textbook chapters, and online modules. Another passion of Dr. Feuerstadt is teaching, frequently giving lectures locally, regionally and nationally. He holds a clinical appointment as an Assistant Clinical Professor of Medicine at the Yale University School of Medicine and is a full-time attending physician at the Gastroenterology Center of Connecticut seeing patients with a broad spectrum of clinical gastroenterological diseases.

Dr. Feuerstadt attended the Weill Medical College of Cornell University in Manhattan for medical school and completed his residency in internal medicine at New York-Presbyterian Hospital/Weill Cornell. His clinical fellowship training was completed at Montefiore Medical Center in the Bronx, New York.

Clostridioides difficile infections (AKA C. diff., C.difficile, CDI) and Microbiome modification.
Dr Oneto is also Co-Director of the C.diff. Community Global Support program offered by the
C Diff Foundation.  Dr. Oneto appears regularly on Doctor Radio on Sirius Xm
and C. diff. Spores and More Radio (cdiffradio.com).

About C.difficile

It is the most common Healthcare-associated infection affecting an estimated 450,000 people annually in the United States alone with ~28,000 deaths from complications of this infection. This infection accounts for ~16% of all healthcare-associated infections.

In the USA: Nearly half a million Americans suffer from Clostridioides difficile (C. diff.) infections in a single year according to a study released on February 25, 2015, by the Centers for Disease Control and Prevention (CDC).

**Approximately 29,000 patients died within 30 days of the initial diagnosis of C. difficile. Of those, about 15,000 deaths were estimated to be directly attributable to C. difficile infections (CDI), making C. difficile a very important cause of infectious disease death in the United States alone. More than 80 percent of the deaths associated with C. difficile occurred among Americans aged 65 years or older. C. difficile causes an inflammation of the colon and deadly diarrhea.

C. difficile clade A, Able to Withstand Modern Diet and Healthcare Facilities Long Before They Existed

Researchers at The Wellcome Sanger Institute and the London School of Hygiene & Tropical Medicine say they found that C. diff bacteria appears to have broken off into another species, reports StudyFinds.

While the researchers just uncovered the strain, it’s likely been around for tens of thousands of years and is probably the cause of the majority of C.diff infections at hospitals today.

The strain, which is being called C. difficile clade A, was built to withstand modern diet and healthcare facilities way before they existed.

Scientists say that Clostridium difficile (C. diff) is evolving, which could make things more difficult for hospitals that have for years struggled with the bacteria.

The newly discovered strain are problematic because they prefer the sugar-rich diet enjoyed in western countries and can tolerate the cleaning procedures typically carried out at the healthcare facilities in these countries. (*?)

Those involved in the study say it has provided scientists with a better understanding of how bacteria evolves over time. They say the discovery further proves the importance of genomic studies of bacteria.

Another study conducted by the American Society for Microbiology recently found that C. diff is doing a good job of sticking to hospital gowns even after they’ve been treated.

Researchers Find Sulfated glycosaminoglycans and Low-Density Lipoprotein Receptor Contribute To Clostridioides difficile Toxin A Cell Entry

 

Abstract

Clostridium difficile toxin A (TcdA) is a major exotoxin contributing to disruption of the colonic epithelium during C. difficile infection. TcdA contains a carbohydrate-binding combined repetitive oligopeptides (CROPs) domain that mediates its attachment to cell surfaces, but recent data suggest the existence of CROPs-independent receptors. Here, we carried out genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated screens using a truncated TcdA lacking the CROPs, and identified sulfated glycosaminoglycans (sGAGs) and low-density lipoprotein receptor (LDLR) as host factors contributing to binding and entry of TcdA. TcdA recognizes the sulfation group in sGAGs. Blocking sulfation and glycosaminoglycan synthesis reduces TcdA binding and entry into cells. Binding of TcdA to the colonic epithelium can be reduced by surfen, a small molecule that masks sGAGs, by GM-1111, a sulfated heparan sulfate analogue, and by sulfated cyclodextrin, a sulfated small molecule. Cells lacking LDLR also show reduced sensitivity to TcdA, although binding between LDLR and TcdA are not detected, suggesting that LDLR may facilitate endocytosis of TcdA. Finally, GM-1111 reduces TcdA-induced fluid accumulation and tissue damage in the colon in a mouse model in which TcdA is injected into the caecum. These data demonstrate in vivo and pathological relevance of TcdA-sGAGs interactions, and reveal a potential therapeutic approach of protecting colonic tissues by blocking these interactions.

To view abstract in its entirety please click on the following link to be redirected:  https://www.ncbi.nlm.nih.gov/pubmed/31160825?dopt=Abstract&utm_source=dlvr.it&utm_medium=twitter