Tag Archives: Clostrideum difficile

Clostidium difficile Most Recent Research Discussed By ASM and Dr. Alice Guh, MD, MPH of the CDC

Clostridium difficile is an increasingly important problem being faced by clinical microbiologists. From 1993 to 2009, incidence of C. difficile increased fourfold (85,700 cases increased to 336,600 cases) in the United States. Because of this, it has become a significant area of research, as researchers search for better antimicrobial therapies, diagnostic assays, and prevention tactics.   ASM recently invited Alice Guh, MD, MPH, of the Centers for Disease Control and Prevention, to present the most recent C. difficile research as part of the Hot Topics in Clinical Microbiology series*. In her presentation, ‘Update on Clostridium difficile Infection’, Guh first describes the changing epidemiology of C. difficile infections (CDI), updating the data from the CDC’s Emerging Infections Program (EIP) and their long-term surveillance of CDI within the United States.

Guh further reviews current CDI diagnostic testing and its associated challenges. She highlights the benefits and downfalls of traditional enzyme immunoassay to detect C. difficile toxins compared to the nucleic acid amplification tests (NAAT) first put to widespread use in 2009.

Finally, Guh describes the role of asymptomatic carriers in C. difficile transmission. Her review of the literature presents best practices to trace transmission from asymptomatic carriers as well as suggested strategies to stop this transmission.

To read the article in its entirety please click on the following link:

https://www.asm.org/index.php/clinmicro-blog/item/6264-hot-topics-in-clinical-microbiology-clostridium-difficile

 

Study Finds Community – acquired Clostridium difficile (Cdiff) Infection (CDI) Greater Than Hospital-acquired CDI

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ASM Microbe 2016 (Poster 290)

Community-onset CDI cases increased at a higher rate than hospital-acquired cases—accounting for almost half of the cases—in an examination of clinical data from 154 U.S. hospitals over eight years, according to research presented at the ASM Microbe 2016 (Poster 290)

Researchers from Merck and Becton Dickinson wanted to examine this trend, and looked at where CDI began by analyzing clinical data from 154 hospitals from 2008 to 2015.

>> Thank You Merck and Becton Dickinson For Conducting This Study <<

A CDI case was defined as a positive C. difficile toxin or molecular assay of a stool specimen obtained from a patient without a positive assay in the previous eight weeks.

First, they looked at the overall CDI rate in those facilities in that eight-year period and found 154,629 total CDI cases.

Then the teased out whether the case was acquired in the community or hospital. They also dived a little deeper to understand which community cases really were “community” that is there was no hospital stay within a certain time before the onset of disease, explained Andy DeRyke, PharmD, director scientific strategy lead at Merck, and one of the researchers.

They used these three definitions:
Community-onset-community-associated: CDI occurred in an outpatient setting or within three calendar days after hospital admission and the patient had not had an overnight hospital stay in the prior 12 weeks before onset of infection;
Community-onset-hospital-associated: CDI occurred in an outpatient setting or within three days after hospital admission, but the patient had spent at least one night in the hospital in the prior 12 weeks to the onset of infection; and
Hospital-onset: CDI occurred after spending three days in the hospital.

Although not knew information—other studies as well as the Centers for Disease Control and Prevention (CDC) have reported community-acquired infection—they were surprised by how many cases were community acquired.

From 2008 to 2015, the total number of CDI cases increased from 14,686 to 25,273 (72% increase, P<0.01).

Those that were Community-onset-community-associated rose from 6,586 to 13,975 (112%, P<0.01).

While the cases that probably stemmed from a hospital exposure also increased, the rate was much lower, according to Dr. DeRyke.

Those that were community-onset-hospital-associated rose from from 4,545 to 6,524 (44%, P<0.01); while hospital-onset rose from from 3,555 to 4,775 (34%, P<0.01).

The community-onset-community-associated cases accounted for half of overall cases and proportionately increased from 45% in 2008 to 55% in 2015 (P<0.01).

They also looked at cases geographically and found that the Midwest had the highest CDI rate in the country.

“The rates of C. diff are increasing over time,” he said. “Despite all these efforts to eliminate C. diff, it continues to increase.”

Ambulatory patients and caregivers will find the same problems that hospitals have in trying to rid the environment of C. difficile, he said. “The problem is, it’s everywhere,” he said and recommended that any person caring for a patient with CDI make sure that they wash their hands frequently and disinfect with bleach.

https://cdifffoundation.org/hand-washing-updates/

 

To read article in its entirety click on the following link:

http://www.idse.net/Hospital-acquired-infection/Article/06-16/C-diff-Not-Just-a-Hospital-Problem-Anymore/36793

Researchers Make Chemical Changes In the InsP6 Inhibitor To Improve Its Hydrogen Bonding Capabilities With C. difficile Toxins

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Infections with bacterium Clostridium difficile have rapidly become a significant medical problem in hospitals and long-term care facilities. The bacteria cause diarrhea and life-threatening inflammation of the colon by producing toxins that kill the endothelial cells that form the lining of the gut.

Although a natural inhibitor of these toxins, called InsP6, works in the test tube, it is not very efficient when administered orally.

Traditional methods to optimize InsP6 have until now not been successful, but researchers at Baylor College of Medicine have discovered that changing one atom in InsP6 can increase its ability to neutralize the toxins by 26-fold.

The results appear in Science Advances.

“The toxins, called TcdA and TcdB, are very large molecules that kill the cells very efficiently,” said Dr. Tor Savidge, associate professor of pathology and immunology and of pediatrics, director of the Savidge Lab at the Texas Children’s Microbiome Center and senior author of the paper. “It’s like delivering a warhead into the cell. The toxins bind to the cell and the cell internalizes them in a sack of cell membrane called endosome. Not all of the toxin will exit this sack to kill the cell, just the little warhead pokes its head out. Another section of the toxin senses when the warhead is outside the sack and cleaves it. The warhead is released, interferes with basic functions and kills the cell,” said Savidge.

To neutralize the toxins, the researchers targeted the section that senses when the warhead is inside the cell, called allosteric modulator. “The strategy we have tried is to make the toxin ‘think,’ before it binds to and enters the cell, that the warhead is ready to be released, so it releases it prematurely,” said Savidge. When the warhead is released outside the cell, it is neutralized. InsP6, the toxins’ natural inhibitor, works this way, but is not very efficient.

Finding molecules that would bind to the allosteric modulator and trigger the premature release of the warhead involved analyzing and testing half a million molecules listed in large databases. Dr. Numan Oezguen, a member of the Savidge Lab, used virtual drug screening to sift through the databases to identify candidate molecules that most likely would bind to the allosteric modulator. One of his screening strategies consists of creating virtual 3-D structures of the molecules, projecting them on a large screen and using 3-D glasses to determine the most likely interactions between molecules. The molecules whose virtual analysis suggested they would bind to the allosteric modulator were then tested in the lab.

“We found that allosteric mechanisms are very complicated,” said Savidge. “You can find something that binds and you think, well, this is probably a good candidate for this, but it’s not right. It binds, but it doesn’t trigger the premature release of the warhead.”

Far from discouraging their efforts, the results motivated the researchers to better understand what makes interactions between molecules stronger or weaker. Their comprehensive analysis of numerous molecules provided insights into how water contributes to molecular interactions, in particular those involving hydrogen bonds, one of the most important bonds between molecules. The roles of water and hydrogen bonding had not been considered in this way before.

“When you take water into consideration you need to acknowledge that it can form hydrogen bonds, which may or may not compete or interfere with those formed between other molecules such as C. difficile toxins and their inhibitors, which interact in the gut, surrounded by water,” said Savidge.

“Before we considered the role of water, the predominant idea was that to strengthen the interaction between molecules the ability to form hydrogen bonds had to be made as strong as possible in the drug. It turns out this is not the case,” said Oezguen. Many times drugs designed to be able to make strong hydrogen bonds bind poorly to their targets.

The researchers discovered that to enhance the binding of a drug to its target, both sides of the hydrogen bond, the side on the drug and the one on the target, have to have either significantly stronger or significantly weaker hydrogen bonding capabilities.

On the other hand, a mixed strong-weak hydrogen bond pairing decreases the overall binding of the drug to its target, in some cases by 3 million fold. The decrease in binding is the result, the researchers propose, of water molecules forming hydrogen bonds with the drug and its target, therefore preventing the drug and the target from forming hydrogen bonds between them.

With all this information in hand, the researchers proceeded to make chemical changes in the InsP6 inhibitor to improve its hydrogen bonding capabilities with
C. difficile toxins.

One of the modifications, changing one single atom in InsP6, strengthened InsP6 binding to the allosteric modulator by 26-fold. This observation builds on a report published by Savidge in Science last year exploring the role of water interactions in the origin of enzymatic catalytic power.

Plans are currently underway to exploit these fundamentally new concepts in the precision design of future therapeutic applications.

Other contributors to this work are Deliang Chen, now in Gannan Normal University, China, who contributed conceptual and theoretical proof of the hydrogen bonding pairing principle; Petri Urvil from Baylor performed lab studies; Colin Ferguson from Echelon Biosciences, Inc. synthesized the more efficient inhibitor; and Sara Dann from the University of Texas Medical Branch in Galveston, contributed animal studies.

This work was supported by grants RO1AI100914 and DK56338 from the National Institute of Allergy and Infectious Diseases and the National Institute of Diabetes and Digestive and Kidney Diseases at the NIH, and the National Science Foundation of China (21473041).

Source: https://www.bcm.edu/

 

To read the article in its entirety click on the following link:

http://www.azom.com/news.aspx?newsID=45377

7th European Spores Conference Royal Holloway, University of London April 18-20, 2016

We are pleased to share the following 7th European Spores Conference information with you.  If you have any questions, please contact Professor Simon M. Cutting directly  at s.cutting@rhul.ac.uk

18th – 20th of April 2016

The European Spores Conference 2016

AccessDIFICID (fidaxomicin) Is A Support Program For Patients Prescribed DIFICID®

Dificid (fidaxomicin)  Product Access and Support Information:

AccessDIFICID is a support program for patients who have been prescribed DIFICID® (fidaxomicin) tablets.

Case managers are available M-F, 8 am – 8 pm; SAT, 9 am – 1 pm, ET, to provide the following information and support:

  • Research your insurance benefits
  • Obtain information about your out-of-pocket costs
  • Provide information on co-pay assistance options
  • Provide a referral to the Patient Assistance Program (PAP)
  • Provide information about local pharmacies that stock DIFICID and/or options for overnight deliveries of DIFICID, where available, to the location of your choice
  • Answer questions about filling out the AccessDIFICID Enrollment Form

Getting started is simple

  • Download and complete the appropriate sections of the AccessDIFICID Enrollment Form with your health care provider
  • You or your health care provider can fax the completed form to 1-888-997-9329
  • A program representative will then contact you and your health care provider’s office
After your intake form has been processed, you will receive a phone call from an AccessDIFICID case manager, who will work with you throughout the process. You may also contact a case manager at 1-844-282-4782 (M-F, 8 am – 8 pm; SAT, 9 am – 1 pm, ET).

 For continued information for AccessDIFICID please click on the following link:

http://www.accessdificid.com/

 

*The C Diff Foundation does not endorse this or any medical and non-medical treatment available for the
treatment of a C. difficile infection.  All possible treatment options are strictly information
based and for the general public and for general knowledge.   Discuss all treatment options
with the physician/s providing care for and and all diagnosis.  *

Study Advances Development of Preventative Approach for C. difficile Infection – Synthetic Biologics Initiates Phase 2a Clinical Trial of SYN-004 to Protect the Microbiome and Prevent C. difficile

Study Advances Development of Preventive Approach for C. difficile Infection
Synthetic Biologics, Inc..   a developer of pathogen-specific therapies for serious infections and diseases, with a focus on protecting the microbiome,  announced on March 30, 2015, the initiation of a Phase 2a clinical trial to evaluate the gastrointestinal (GI) antibiotic-degrading effects and the safety of SYN-004, the Company’s investigational oral beta-lactamase enzyme designed to protect the microbiome and prevent C. difficile infection (CDI). C. difficile is the leading type of hospital acquired infection and is frequently associated with intravenous (IV) antibiotic treatment. Beta-lactam antibiotics are a mainstay in hospital infection management, and include commonly used penicillin and cephalosporin antibiotics, such as ceftriaxone.
“We are excited to start our Phase 2a trial of SYN-004 on schedule. Synthetic Biologics believes SYN-004 holds the potential to protect the microbiome from the damaging effects of antibiotics and dramatically reduce C. difficile infections through prevention vs. treatment,” said Jeffrey Riley, Chief Executive Officer of Synthetic Biologics. “We anticipate reporting topline results from this Phase 2a clinical trial during the second quarter of 2015, and initiating the Phase 2b clinical trial in the second half of this year.”
The U.S. Centers for Disease Control and Prevention (CDC) has categorized C. difficile as an “urgent public health threat,” and has stated the need for research to better understand the role of normal gut bacteria. SYN-004 is intended to block the unintended harmful effects of antibiotics within the GI tract and maintain the natural balance of the gut microbiome, potentially preventing the 1.1 million C. difficile infections and 30,000 C. difficile-related deaths  in the United States each year. During 2012, approximately 14 million U.S. patients received approximately 118 million doses of IV beta-lactam antibiotics that could be inactivated in the GI tract by SYN-004.

https://cdifffoundation.org/2015/02/25/c-diff-new-cdc-study-national-burden-of-clostridium-difficile-c-diff-infections/
The Phase 2a randomized, multi-center, open-label study is expected to evaluate the ability of two different dose strengths of SYN-004 to degrade residual IV ceftriaxone in the GI tract of up to 20 healthy participants with functioning ileostomies, without affecting the concentrations of IV ceftriaxone in the bloodstream. The study consists of two treatment phases for all participants: 1) the administration of IV ceftriaxone alone, and 2) the administration of one of two doses of oral SYN-004 and IV ceftriaxone. Chyme samples will be collected from the participants to measure the ability of SYN-004 to degrade the residual antibiotic. Participants will be enrolled at up to four trial sites located in the United States and Canada.

For more information visit Synthetic Biologics website:

www.syntheticbiologics.com

 

*Please note – The C Diff Foundation does not endorse this product or any product and this posting is strictly for informational purposes only.

C. diff. Infection Support and Information Available

cdiffphasehere

Do you have questions about a                          C. diff.   infection?

Call 1-844-FOR-CDIF  (367-2343)

And speak with a information specialist for          assistance regarding  C. diff. infection prevention, treatments, and environmental safety products available.

 

 

* Disclaimer:  Please do not cease in seeking medical treatment and medical care if any C. diff. symptoms are noticed or continue. Please see your Primary Care Physician or go to the nearest Clinic/ER for medical treatment. The C Diff Foundation does not provide assessments or diagnosis and is not liable for decisions made solely based from the information provided here or through the hotline or archived on the website. The foundation does not provide ancillary assistance with travel, or lodging. Information shared is for educational use only and to raise C. diff.  awareness in prevention, treatments, and environmental safety worldwide.  Thank you