Tag Archives: Cdiff research

Clostridium difficile Infection Research and Development Community – Update On Antibody-based Immunotherapies

An update on antibody-based immunotherapies for Clostridium difficile infection

Authors Hussack G, Tanha J

Greg Hussack,1 Jamshid Tanha1–3

1Human Health Therapeutics Portfolio, National Research Council Canada, Ottawa, 2School of Environmental Sciences, University of Guelph, Guelph, 3Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada

Abstract: Clostridium difficile continues to be one of the most prevalent hospital-acquired bacterial infections in the developed world, despite the recent introduction of a novel and effective antibiotic agent (fidaxomicin). Alternative approaches under investigation to combat the anaerobic Gram-positive bacteria include fecal transplantation therapy, vaccines, and antibody-based immunotherapies. In this review, we catalog the recent advances in antibody-based approaches under development and in the clinic for the treatment of C. difficile infection. By and large, inhibitory antibodies that recognize the primary C. difficile virulence factors, toxin A and toxin B, are the most popular passive immunotherapies under investigation. We provide a detailed summary of the toxin epitopes recognized by various antitoxin antibodies and discuss general trends on toxin inhibition efficacy. In addition, antibodies to other C. difficile targets, such as surface-layer proteins, binary toxin, motility factors, and adherence and colonization factors, are introduced in this review.

Click on the following link to access article in its entirety:

https://www.dovepress.com/an-update-on-antibody-based-immunotherapies-for-clostridium-difficile–peer-reviewed-article-CEG

U.Va.’s Division of Infectious Diseases and International Health Could Lead To a New Treatment For C. diff. Infection (CDI)

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Every year, about half a million patients are infected by Clostridium difficile, an otherwise harmless bacterium that can multiply out of control when the use of antibiotics upsets the balance of microorganisms in the gut. In 2011, about 15,000 deaths were directly attributable to the infection, according to a recent study by the federal Centers for Disease Control and Prevention (CDC).

Current probiotic treatments, which promote the growth of helpful bacteria, have been ineffective against the infection, also known as C. diff.

But work being done at U.Va.’s Division of Infectious Diseases and International Health could lead to a new treatment by the end of the calendar year, according to Dr. Bill Petri, chief of the division. That’s an unusually optimistic estimate in medical research, where scientific breakthroughs predate new treatments by several years.

“Some of these advanced probiotics are actually being tested today in the clinic for their role,” Petri said. “We’re actually participating in advanced clinical trials at U.Va.”

Immunologist Erica L. Buonomo was the driving force behind the new discovery, Petri said, which has to do with the role of white blood cells in protecting against C. diff.

Buonomo found that a particular type of white blood cells, called eosinophils, act as a barrier against the infection, which breaks down the lining of the gut. These eosinophils are recruited by a protein called IL-25. A serious C. diff infection kills eosinophils, allowing the bacteria to enter the gut.

The researchers found that gut bacteria stimulate the production of IL-25, so the right probiotic could help with the production of protective eosinophils.

“We identified a pathway in the immune response that reduces the severity of an infection,” Buonomo said. “When we activate this pathway, we find mice are a lot less sick.”

The discovery would be especially helpful for elderly patients, who are most at risk. It also could have larger implications in the world of microbiology.

Eosinophils are best known for their role in allergic reactions and asthma attacks, when a high number of eosinophils cause inflammation.

The function of these cells was not entirely clear before Buonomo’s discovery. She believes this knowledge could help doctors fight other types of gastrointestinal disorders, such as irritable bowel syndrome.

U.Va. is now working on a probiotic with a Boston-based firm called Seres Therapeutics 

The finished product will be tested in Charlottesville, Petri said.

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

Stop the Spread of Antibiotic Resistance and C. difficile Infections

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Antibiotic-resistant germs cause more than 2 million illnesses and at least 23,000 deaths each year in the US.

Up to 70% fewer patients will get CRE over 5 years if facilities coordinate to protect patients.

Preventing infections and improving antibiotic prescribing could save 37,000 lives from drug-resistant infections over 5 years.

Problem:  Germs spread between patients and across health care facilities.

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Antibiotic resistance is a threat.

 

  • Nightmare germs called CRE (carbapenem-resistant Enterobacteriaceae) can cause deadly infections and have become resistant to all or nearly all antibiotics we have today. CRE spread between health care facilities like hospitals and nursing homes when appropriate actions are not taken.
  • MRSA (methicillin-resistant Staphylococcus aureus) infections commonly cause pneumonia and sepsis that can be deadly.
  • The germ Pseudomonas aeruginosa can cause HAIs, including bloodstream infections. Strains resistant to almost all antibiotics have been found in hospitalized patients.
  • These germs are some of the most deadly resistant germs identified as “urgent” and “serious” threats.
C. difficile infections are at historically high rates.
  • C. difficile (Clostridium difficile), a germ commonly found in health care facilities, can be picked up from contaminated surfaces or spread from a healthcare provider’s hands.
  • Most C. difficile is not resistant to antibiotics, but when a person takes antibiotics, some good germs are destroyed. Antibiotic use allows C. difficile to take over, putting patients at high risk for deadly diarrhea.
Working together is vital.
  • Infections and antibiotic use in one facility affect other facilities because of patient transfers.
  • Public health leadership is critical so that facilities are alerted to data about resistant infections, C. difficile, or outbreaks in the area, and can target effective prevention strategies.
  • When facilities are alerted to increased threat levels, they can improve antibiotic use and infection control actions so that patients are better protected.
  • National efforts to prevent infections and improve antibiotic prescribing could prevent 619,000 antibiotic-resistant and C. difficile infections over 5 years.

 

  • “Patients and their families may wonder how they can help stop the spread of infections,” says Michael Bell, M.D., deputy director of CDC’s Division of Healthcare Quality Promotion. “When receiving health care, tell your doctor if you have been hospitalized in another facility or country, wash your hands often, and always insist that everyone have clean hands before touching you.”

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Antibiotic-resistant germs, those that no longer respond to the drugs designed to kill them, cause more than 2 million illnesses and at least 23,000 deaths each year in the United States. C. difficile caused close to half a million illnesses in 2011, and an estimated 15,000 deaths a year are directly attributable to C. difficile infections.

 The report recommends the following coordinated, two-part approach to turn this data into action that prevents illness and saves lives:

  1. Public health departments track and alert health care facilities to drug-resistant germ outbreaks in their area and the threat of germs coming from other facilities, and
  2. Health care facilities work together and with public health authorities to implement shared infection control actions to stop the spread of antibiotic-resistant germs and C. difficile between facilities.

“Antibiotic resistant infections in health care settings are a growing threat in the United States, killing thousands and thousands of people each year,” said CDC Director Tom Frieden, M.D., M.P.H. “We can dramatically reduce these infections if health care facilities, nursing homes, and public health departments work together to improve antibiotic use and infection control so patients are protected.”

The promising news is that CDC modeling projects that a coordinated approach—that is, health care facilities and health departments in an area working together—could prevent up to 70 percent of life-threatening carbapenem-resistant Enterobacteriaceae (CRE) infections over five years. Additional estimates show that national infection control and antibiotic stewardship efforts led by federal agencies, health care facilities, and public health departments could prevent 619,000 antibiotic-resistant and C. difficile infections and save 37,000 lives over five years.

During the next five years, with investments, CDC’s efforts to combat C. difficile infections and antibiotic resistance under the National Strategy to Combat Antibiotic Resistant Bacteria, in collaboration with other federal partners, will enhance national capabilities for antibiotic stewardship, outbreak surveillance, and antibiotic resistance prevention. These efforts hold the potential to cut the incidence of C. difficile, health care CRE, and MRSA bloodstream infections by at least half.

The proposed State Antibiotic Resistance Prevention Programs (Protect Programs) would implement this coordinated approach. These Protect Programs would be made possible by the funding proposed in the President’s FY 2016 budget request, supporting work with health care facilities in all 50 states to detect and prevent both antibiotic-resistant germs and C. difficile infections. The FY 2016 budget would also accelerate efforts to improve antibiotic stewardship in health care facilities.

 

C. diff. Infection Prevention Study: Phase 2 Study SER-109 by Seres Therapeutics; First Patient Dosed for the Prevention of Recurrent C. diff. Infection in Adults

* In The News *

Seres Therapeutics, Inc., a leading microbiome therapeutics platform company, announced on May 28th, 2015 the enrollment and dosing of the first patient in its Phase 2 clinical study of SER-109, an investigational oral microbiome therapeutic for the prevention of recurrent Clostridium difficile infection (CDI) in adults.

The objective of the Phase 2 study is to further assess the efficacy and safety of SER-109, Seres’ leading development candidate.

“Recurrent CDI is a rapidly growing problem in the U.S., and antibiotics are currently the only FDA-approved treatment option,” said Roger Pomerantz, Chairman, President and CEO of Seres. “For many patients, antibiotics may exacerbate the problem by inducing or prolonging an imbalance of the microbiome and creating the conditions that support disease recurrence. We are excited about evaluating the potential of SER-109 to correct the microbiome and address this critical patient need.

“The start of our Phase 2 study is an important milestone for patients, and for Seres.

Our earlier studies suggest that SER-109 is a potentially transformative therapeutic for tens of thousands of patients each year, validating our conviction that treating dysbiosis of the microbiome enables us to address the underlying cause of disease and bring about rapid improvements in health.”

Results from the Phase 1b/2 study of SER-109 in recurrent CDI patients showed that 87 percent of patients met the primary study endpoint and 97 percent of patients achieved a clinical cure, which was defined as the absence of CDI requiring antibiotic treatment during the eight-week period after SER-109 dosing.

The Phase 2 study is a multicenter, randomized, placebo-controlled study that will evaluate the efficacy and safety of SER-109. The primary outcome measure is the absence of clinically-significant CDI through eight weeks following administration of SER-109 compared to placebo. SER-109 will be administered orally as a single dose, following the standard of care antibiotics for CDI. The study is actively enrolling and will be conducted at approximately 35 centers across the U.S. The read-out from the Phase 2 study is currently expected in the middle of 2016.

About SER-109

SER-109 is the lead Seres Ecobiotic® microbiome therapeutic in clinical testing for the treatment of recurrent Clostridium difficile infection (CDI). SER-109 was developed utilizing the Seres Microbiome Therapeutics™ platform that provides deep insight into the ecologies of disease and then identifies microbial compositions that can catalyze a shift to health. CDI is a rapidly growing problem associated with antibiotic use. Approximately 85,000 to 110,000 CDI patients in the U.S. are expected to have more than one recurrence.

About Seres Therapeutics, Inc.

Seres Therapeutics, Inc. is a leading microbiome therapeutics platform company developing a novel class of biological drugs that are designed to treat disease by restoring the function of a dysbiotic microbiome.

 

For article in its entirety:

http://finance.yahoo.com/news/seres-therapeutics-inc-announces-first-113000601.html

 

 

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

Loyola Int’l C. diff. Research, Dr. Dale Gerding, MD Makes Important Breakthrough Towards the Prevention of Recurring C.diff. Infection

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In what is a major step towards the prevention of recurring bouts of Clostridium difficile (C.diff.) infection, an international team led by Dr. Dale Gerding, MD, Hines Veterans Administration (VA) research physician and professor of Medicine at Loyola University Chicago Stritch School of Medicine, has shown that giving spores of non-toxic C.diff. by mouth is effective in stopping repeated bouts of C.diff. infection which occurs in 25-30 percent of patients who suffer an initial episode of diarrhea or colitis.

 

The study is published in the May 5 issue of the Journal of American Medical Association (JAMA) and is the focus of a JAMA-produced video.

“The results of this study are very gratifying because the preclinical laboratory and patient studies were all done through our VA research program supported by the Department of Veterans Affairs Research Service,” says Gerding. “Results of this study confirm findings of earlier studies that showed that if we can establish non-toxic C.diff. as a resident of the gut of the patient, that we can protect the patient from infection by the toxic strains of C.diff..” Viropharma and Shire pharmaceutical companies supported the clinical trials.

These results warrant additional study to confirm that treatment with non-toxic C.diff. spores can reduce recurrent C.diff. infection and prevent a first episode of C.diff. infection in those who are taking any antibiotics and are at high risk of infection, he added.

Gerding and an international team of infectious disease researchers, including those at Loyola University Medical Center (LUMC), randomly assigned 168 adult patients with C.diff. infection who had been treated for their infection with antibiotics to receive doses of 10 thousand or 10 million spores per day of non-toxic C.diff. in liquid form for 7 or 14 days, or to receive an identical placebo. Of those assigned any dose of non-toxic C.diff. , 11 percent experienced a repeat of infection within 42 days compared with 30 percent of those given a placebo, a statistically significant reduction. For the most favorable dose tested, 10 million spores a day for 7 days, the recurrence of C.diff. infection was reduced to 5 percent.

Healthcare-acquired infections (HAI) including a leading HAI, C.diff. causes severe diarrhea and inflammation of the lower bowel or colon, continues to escalate in frequency and severity in the U.S.

According to the Centers for Disease Control and Prevention (CDC) report published in
February 2015, almost 500,000 C.diff. infections occurred in the U.S. in 2011, with 83,000 recurrences and 29,000 deaths within 30 days of diagnosis.  Older adults taking antibiotics and who receive care at medical institutions have a higher risk at acquiring this infection.

Cheryl O’Riordan, who has had repeated bouts of C.diff. infection, said having C.diff. made her visit the bathroom on an average of 10 times per day. “Before receiving effective treatment, I was unable to leave the house,” says the active cyclist, skier and hiker. O’Riordan went into remission after being treated successfully at LUMC. “I am back cycling more than 3 miles every day and have several major adventure trips planned.”

Gerding, who has published more than 135 studies on C.diff. is considered one of the leading international experts on C.diff..

Stuart Johnson, MD, infectious disease specialist at LUMC, is also the director of research at Hines VA hospital. Together Gerding and Johnson have partnered on C.diff. research for almost three decades, involving many LUMC patients.

“The study offers real hope for those debilitated by recurring bouts of C.diff.,” says Johnson “This study represents a novel and potentially highly effective bacteriotherapy approach to restoring colonization resistance against toxic strains of C.diff. in these patients,” he adds.

Loyola University Health System is recognized internationally as a leader in infection control and prevention.

LUMC is one of a few select hospitals who invest in universal screening of all inpatients for MRSA. Loyola was one of the first institutions to require all staff to have mandatory flu shots as a condition of employment. Loyola was one of several academic hospitals that participated in this recent benchmark international study.

 

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

http://www.eurekalert.org/pub_releases/2015-05/luhs-lso050115.php