Tag Archives: C difficile research and development

“C. diff. Spores and More ” C diff Radio Returns To Live Broadcasting Tuesday, January 19th

 

Welcome to Season 2

C. diff. Spores and More

Join us for live broadcasting  on Tuesday January 19th, 2016 at 10 a.m. Pacific Time,
11 a.m. Mountain Time, 12 p.m. Central Time,   1 p.m. Eastern Time.

 

Programming for Tuesday, January 19th:
“C. difficile Infections; The What, Where and How.”

This episode of “C. diff. Spores and More” is focused on
“C. difficile Infections; The What, Where and How.”
What is it,  What can be done to prevent acquiring it,
Where is it acquired, Where can clinicians and patients
learn more about this infection, How is it being prevented at home
and in the hospitals, How CDI’s are being treated, and How to learn more about the
prevention, treatments, and environmental safety products available
With our special guests:

 

 

Dr. Caterina Oneto,, MD

 

 

 

 

 

and Dr. Paul Feuerstadt, MD,
Both professors and physicians specializing in Gastroenterology with
a wealth of knowledge and experience treating patients
with a CDI and through ongoing scientific/medical research.

 

 

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We are pleased to share  “C. diff. Spores and More ”  with you because, as advocates
of C. diff., we know the importance of this cutting-edge new weekly radio show
and what it means for our Foundation’s community worldwide.

Hard Facts: Deaths and illnesses are much higher than reports have shown Nearly half a million Americans suffered from Clostridium difficile (C. diff.) infections in a single year according to a study released today, February 25, 2015, by the Centers for Disease Control and Prevention (CDC).

Previous studies indicate that C. diff. has become the most common
microbial cause of Healthcare-Associated Infections found in U.S. hospitals
driving up costs to $4.8 billion each year in excess health care costs in acute
care facilities alone. Approximately two-thirds of C. diff. infections
were found to be associated with an inpatient stay in a health care facility,
only 24% of the total cases occurred in patients while they were hospitalized.
The study also revealed that almost as many cases occurred in nursing homes as
in hospitals and the remainder of individuals acquired the
Healthcare-Associated infection, C. diff., recently discharged from
a health care facility.

This new study finds that 1 out of every 5 patients with the
Healthcare-Associated Infection (HAI), C. diff., experience
a recurrence of the infection and 1 out of every 9 patients over the
age of 65 diagnosed with a HAI – C. diff. infection died
within 30 days of being diagnosed. Older Americans are quite vulnerable
to this life-threatening diarrhea infection. The CDC study also found
that women and Caucasian individuals are at an increased risk of
acquiring a C. diff. infection.
The CDC Director, Dr. Tom Frieden, MD, MPH said, “C. difficile
infections cause immense suffering and death for thousands of Americans
each year.” “These infections can be prevented by improving antibiotic
prescribing and by improving infection control in the health care system.
CDC hopes to ramp up prevention of this deadly infection by supporting
State Antibiotic Resistance Prevention Programs in all 50 states.”

“This does not include the number of C. diff. infections taking place
and being treated in other countries.”  “The  C Diff Foundation supports hundreds
of communities by sharing the Foundation’s mission and
Raising C. diff. awareness to healthcare professionals,patients,
families,  and communities working towards a shared goal ~  witnessing a
reduction of newly diagnosed C. diff. cases by 2020 .”
” The C Diff Foundation volunteer Advocates are truly appreciated and stand
with the Foundation members creating positive changes through
time and dedication in “Raising C. diff. awareness ”  worldwide.

C. diff. Spores and More “ spotlights world
renowned topic experts, research scientists, healthcare professionals,
organization representatives, C. diff. survivors, board members,
and C Diff Foundation volunteer advocates  – all working together to
create positive changes in the C. diff. community and more.

Through their interviews, the C Diff Foundation mission will
connect, educate, and empower our worldwide listeners.

Do you have Questions?  Email them to the C Diff Foundation at

info@cdifffoundation.org or through the show page portal.
Questions will be addressed  by the show’s Medical Correspondent, Dr. Fred Zar, MD, FACP,
Dr. Fred Zar is a Professor of Clinical Medicine,
Vice Head for Education in the Department of Medicine, and Program Director of the Internal Medicine Residency
at the University of Illinois at Chicago.  Over the last two decades he has
been a pioneer in the study of the treatment of Clostridium difficile disease
and the need to stratify patients by disease severity.

 

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Programming for “C. diff. Spores and More ”   is made
possible through our official Corporate Sponsor;  Clorox Healthcare

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Moving the Dial A Little Closer To Better Treatment and Prevention Of C. diff. Infections

 

 

 

Researchers at Vanderbilt University Medical Center have obtained the crystal structure of a toxin from the bacterium Clostridium difficile (C. diff)   a leading hospital-acquired infection  in the United States.

“This is basic science. I think it gives a framework for understanding how, once you do have an infection, the toxins are causing the disease,” says senior author D. Borden Lacy, PhD, associate professor of Pathology, Microbiology and Immunology and of Biochemistry.

Like anthrax, diphtheria and botulism, C. diff infection is a toxin-mediated disease. The bacterium actually produces two similar toxins, toxin A and toxin B. But unlike the other infections, there is as yet no vaccine or other treatment that can effectively block C. diff toxins.

Meanwhile, C. diff has become a major public health menace. In 2011, the bacterium caused nearly half a million infections in the United States, and approximately 29,000 people died from intestinal complications, including a form of colitis, within a month of the initial diagnosis.

In 2012 and 2013, Lacy and her colleagues reported the mechanism by which toxin B kills cells. Earlier this year, they reported the identification of the cellular receptor that binds the toxin.

After binding to their receptors, the toxins are enveloped by an endosome, or tiny vesicle. Through a pore it drills into the cell membrane, each toxin then sends pieces of itself with two enzymatic activities into the cell. The enzymes modify the activity of cellular proteins, ultimately killing the cell.

In the current study, the researchers, led by Lacy’s research assistant, Stacey Rutherford, generated the crystal structure of C. diff toxin A. Benjamin Spiller, PhD, associate professor of pharmacology and of pathology, microbiology and immunology, also contributed to the crystallography.

At Argonne National Laboratory outside Chicago, the researchers bounced a highly focused X-ray of a specific wavelength off the crystal. The resulting diffraction pattern was then converted using computational methods into a model of the toxin.

They found that one small section of the toxin is “highly conserved,” meaning that its sequence of amino acids is identical to the same sequence in other Clostridium species.

This “suggests that antibodies specific for this conserved region could provide protection against multiple toxin-mediated clostridium infections and points to a generalizable strategy for generating safe vaccine antigens for this class of toxins,” they conclude.

In addition, Nicole Chumbler, a graduate student in the Lacy lab who is now a postdoctoral fellow at Harvard Medical School, found that zinc is bound to the toxin and is required for its activity. Small molecules targeting the zinc-binding enzyme could block the toxin’s effects.

Much remains to be discovered, Lacy says, but each study moves the dial a little closer to better treatment and prevention of C. diff infections.

 

The research was supported in part by National Institutes of Health grants AI095755 and GM042569.

 

Source: Vanderbilt University Medical Center

 

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

 

http://www.infectioncontroltoday.com/news/2016/01/researchers-closer-to-a-better-treatment-for-clostridium-difficile.aspx

 

 

Asymptomatic carriers of toxigenic C. difficile in long-term care

Asymptomatic carriers of toxigenic C. difficile in long-term care facilities: a meta-analysis of prevalence and risk factors.

Abstract

BACKGROUND:

The impact of Clostridium difficile colonization in C. difficile infection (CDI) is inadequately explored. As a result, asymptomatic carriage is not considered in the development of infection control policies and the burden of carrier state in long-term care facilities (LTCFs) is unknown.

PURPOSE:

To explore the epidemiology of C. difficile colonization in LTCFs, identify predisposing factors and describe its impact on healthcare management.

DATA SOURCES:

PubMed, Embase and Web of Science (up to June 2014) without language restriction, complemented by reference lists of eligible studies.

STUDY SELECTION:

All studies providing extractable data on the prevalence of toxigenic C. difficile colonization among asymptomatic residents in LTCFs.

DATA EXTRACTION:

Two authors extracted data independently.

STATISTICAL METHODS:

The pooled colonization estimates were calculated using the double arcsine methodology and reported along with their 95% random-effects confidence intervals (CIs), using DerSimonian-Laird weights. We assessed the impact of patient-level covariates on the risk of colonization and effects were reported as odds ratios (OR, 95% CI). We used the colonization estimates to simulate the effective reproduction number R through a Monte Carlo technique.

RESULTS:

Based on data from 9 eligible studies that met the specified criteria and included 1,371 subjects, we found that 14.8% (95%CI 7.6%-24.0%) of LTCF residents are asymptomatic carriers of toxigenic C. difficile. Colonization estimates were significantly higher in facilities with prior CDI outbreak (30.1% vs. 6.5%, p = 0.01). Patient history of CDI (OR 6.07; 95% CI 2.06-17.88; effect derived from 3 studies), prior hospitalization (OR 2.11; 95% CI 1.08-4.13; derived from 3 studies) and antimicrobial use within previous 3 months (OR 3.68; 95% CI 2.04-6.62; derived from 4 studies) were associated with colonization. The predicted colonization rate at admission was 8.9%.

CONCLUSION:

Asymptomatic carriage of toxigenic C. difficile represents a significant burden in LTCFs and is associated with prior CDI outbreaks in the facility, a history of CDI, prior hospitalization and antimicrobial use. These findings can impact infection control measures at LTCFs.

To read this article/abstract in its entirety click on the link below:

http://www.ncbi.nlm.nih.gov/pubmed/25707002

C. diff. Research and Development Community October 2015

Here is the latest from the Clostridium difficile research community

 

 

 

Serum 25-hydroxyvitamin D levels are not associated with adverse outcomes in                        Clostridium difficile infection

Clostridium difficile infection (CDI) is a significant source of healthcare-associated morbidity and mortality. This study investigated whether serum 25-hydroxyvitamin D is associated with adverse outcomes from CDI. Patients with CDI were prospectively enrolled. Charts were reviewed and serum 25-hydroxyvitamin D was measured. The primary outcome was a composite definition of severe disease: fever (temperature >38°C), acute organ dysfunction, or serum white blood cell count >15,000 cells/µL within 24-48 hours of diagnosis; lack of response to therapy by day 5; and intensive care unit admission; colectomy; or death within 30 days. Sixty-seven patients were included in the final analysis. Mean (±SD) serum 25-hydroxyvitamin D was 26.1 (±18.54) ng/mL. Severe disease, which occurred in 26 (39%) participants, was not associated with serum 25-hydroxyvitamin D [odds ratio (OR) 1.00; 95% confidence interval (CI) 0.96-1.04]. In the adjusted model for severe disease only serum albumin (OR 0.12; 95%CI 0.02-0.64) and diagnosis by detection of stool toxin (OR 5.87; 95%CI 1.09-31.7) remained independent predictors. We conclude that serum 25-hydroxyvitamin D is not associated with the development of severe disease in patients with CDI.

For full article click on the link below:

http://www.pagepress.org/journals/index.php/idr/article/view/5979

 

Clostridium difficile is a Gram-positive spore-forming pathogen and a leading cause of nosocomial diarrhea. C. difficile infections are transmitted when ingested spores germinate in the gastrointestinal tract and transform into vegetative cells. Germination begins when the germinant receptor CspC detects bile salts in the gut. CspC is a subtilisin-like serine pseudoprotease that activates the related CspB serine protease through an unknown mechanism. Activated CspB cleaves the pro-SleC zymogen, which allows the activated SleC cortex hydrolase to degrade the protective cortex layer. While these regulators are essential for C. difficile spores to outgrow and form toxin-secreting vegetative cells, the mechanisms controlling their function have only been partially characterized. In this study, we identify the lipoprotein GerS as a novel regulator of C. difficile spore germination using targeted mutagenesis. A gerS mutant has a severe germination defect and fails to degrade cortex even though it processes SleC at wildtype levels. Using complementation analyses, we demonstrate that GerS secretion, but not lipidation, is necessary for GerS to activate SleC. Importantly, loss of GerS attenuates the virulence of C. difficile in a hamster model of infection. Since GerS appears to be conserved exclusively in related Peptostreptococcaeace family members, our results contribute to a growing body of work indicating that C. difficile has evolved distinct mechanisms for controlling the exit from dormancy relative to B. subtilis and other spore-forming organisms.

For full article click on the link below:

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005239

 

XBiotech  the world’s leading developer of next-generation True Human therapeutic antibodies, announced today the launch of a research and development program to develop a first-in-class oral monoclonal antibody against Clostridium difficile (C. difficile) infection. Using its proprietary True Human technology, the Company has begun screening human blood samples from donors to identify and clone a therapeutic antibody candidate from individuals with natural immunity to C. difficile infection.

For full article click on the link below:

In a 1-year survey at a university hospital we found that 20·6% (81/392) of patients with antibiotic associated diarrohea where positive for C. difficile. The most common PCR ribotypes were 012 (14·8%), 027 (12·3%), 046 (12·3%) and 014/020 (9·9). The incidence rate was 2·6 cases of C. difficile infection for every 1000 outpatients.
For full article click on the link below:

http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=10011117&fileId=S0950268815002459

Microbiota Changes Predict Treatment Failure
Infection with C. difficile is associated with several adverse outcomes including treatment failure (5% to 35%) but researchers do not know what clinical factors can predict this failure.

Reporting at the American College of Gastroenterology Scientific Meeting in Honolulu, a Mayo Clinic team of researchers looked at which gut microbiota signatures might be useful in determining whether patients will get better.

They defined treatment failure as a non-response to treatment with vancomycin for four days or metronidazole for five days. They looked at 889 patients with primary C. dif in infection (CDI) of whom 60.2% were women and the median age was 54 years. Of these 7% had severe CDI, 70.5% had been treated with metronidazole, 23.8% with vancomycin, and 5.6% with a combination.

Overall 12.5% failed treatment and the rates were similar with each drug.

The researchers looked at clinical factors that might have predicted the failures–age, sex, obesity, prior antibiotic use, and other factors. They found no correlation between having those factors and failing treatment. They did find that patients who responded to treatment had higher quantities of certain bacteria, for instance Faecalibacterium and Bacteroides.

Conversely, the patients who failed treatment had more Streptococcus and Clostridium.

The authors suggest that analyzing these changes in microbiota could be useful. “Gut microbiota signatures may be used to predict treatment response in the absence of reliable clinical predictors,” said Sahil Khanna, MBBS, M S in presenting the study.

For full article click on the link below:

“It Takes A Village” Re: Clostridium difficile (C.diff.) and Healthcare-Associated Infections, By Dr. Rosie D. Lyles, MD,MHA,MSc

“It Takes a Village”
By: Rosie D. Lyles, MD, MHA, MSc, Head of Clinical Affairs for Clorox Healthcare
September 21, 2015

With increasing rates of Clostridium difficile infections (CDI), C. difficile now rivals methicillin-resistance Staphylococcus aureus (MRSA) as the most common organism to cause healthcare-associated infections (HAIs) in the United States. (1) The prevalence of C. difficile infections has more than doubled in U.S. hospitals from 2000 to 2009 (2) and CDI is regarded as one of the serious, expensive, and potentially avoidable consequences of hospitalization. The cost of treating CDI in the hospital is $3427-$9960 (in 2012), and the cost of treating patients with recurrent CDI is $11,631, for a total cost of more than $1.2 billion annually in the United States. (3-4)

In June 2015, the White House spearheaded an executive call to action focused on implementing and improving antibiotic stewardship programs (ASPs) across the continuum of care (acute care facilities, outpatient clinics, doctors’ offices and long-term care facilities). The urgency around this issue stems from the increasing number of antibiotics prescribed, which subsequently breeds multi-drug resistant organisms (MDROs) like C. difficile. Unnecessary or excessive antibiotic use combined with poor infection control practices may increase the spread of C. difficile within a facility and across facilities when infected patients transfer, such as from a hospital to a nursing home. Increasing evidence suggests that contaminated surfaces in healthcare facilities play an important role in the transmission of several key pathogens including C. difficile, vancomycin – resistant enterococci (VRE), MRSA, Acinetobacter baumannii, and norovirus.

In order to reduce HAIs, all hands on deck are required to support a successful infection prevention strategy. In other words, “it takes a village.” Growing up, I remember hearing the phrase, “it takes a village to raise a child,” meaning there is a partnership within a community with several individuals playing a role in the maturation of a youth. Within a hospital, it’s a collaborative team across several departments that implements evidence-based protocols, continues to educate staff and patients, and maintains compliance of infection control strategies/approaches to reduce the risk of a broad range of infections, including CDI. From the C-suite (administrators and senior management) to direct healthcare providers (such as physicians, nurses, aides, and therapists) and environmental staff (EVS); everyone with direct or indirect contact with a patient’s care plays an essential role.

As a healthcare professional, it’s very important for hospitals to focus on the bigger picture when it comes to infection prevention strategy and control. Prioritizing infection control measures for just one or two pathogens of concern is insufficient. At the end of the day, one pathogen doesn’t trump another because patients don’t want an HAI from ANY pathogen! The horizontal approaches aim to reduce the risk of infections due to a broad array of pathogens through implementation of standardized practices that do not depend on patient-specific conditions:

• Proper hand hygiene
Hand hygiene practices in compliance with the Centers for Disease Control and Prevention (CDC) or World Health Organization (WHO) guidelines are a key component in preventing and controlling C. difficile, in addition to many other HAI-causing pathogens.
• Universal use of gloves or gloves and gowns
Donning the correct protective equipment minimizes contact with pathogens. It is also important to follow protocols for properly discarding this equipment.
• Universal decolonization (daily optimal bathing with chlorhexidine gluconate (CHG))
CHG bathing has been shown to decrease the bioburden of microorganisms on the patient, the environment, and the hands of healthcare personnel.
• Antimicrobial stewardship program
Ensuring every patient receives an antibiotic only when needed: the right agent, at the right dose, for the right duration.
• Evidence-based environmental cleaning and disinfection products
At a minimum, effective environmental cleaning involves using cleaners & disinfectants that are registered by the Environmental Protection Agency (EPA). Supplementing manual cleaning with new technology like ultraviolet (UV) light provides an extra layer of protection and the most comprehensive approach. UV has the highest-energy form that can inactivate dangerous and persistent pathogens by eradicating microorganism deoxyribonucleic acid (DNA) that may be left on surfaces, which can be missed with traditional cleaning. Finally, because C. difficile has been found in non-CDI patient rooms, using an EPA-registered sporicidal surface disinfectant to clean all patient rooms (daily and terminal) is great strategy to prevent the spread of the bacteria.

I had the pleasure of attending the CDC’s Environmental Hygiene for Ebola and Other Emerging Pathogens meeting on September 14, 2015, with attendees from academia, private industry, federal employees and health organizations, participated in a roundtable discussion on the research framework needed to determine the public health significance of non-critical environmental surface contamination and provide guidance to healthcare facilities about the methods to reduce the contamination of non-critical environmental surfaces reliably in order to improve patient safety. Every participant present at the meeting agreed that, due to the challenges/barriers that hospitals face with preventing HAIs (both from emerging pathogens and more common pathogens like C. difficile), it takes a village to successfully implement evidence-based protocols, continue to educate and maintain compliance with infection prevention protocols.

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About Rosie D. Lyles, MD, MHA, MSc, Head of Clinical Affairs for Clorox Healthcare

Rosie D. Lyles, MD, MHA, MSc is the Head of Clinical Affairs for the Clorox Professional Products Company where she serves as a research fellow and primary medical science liaison for the healthcare business, supporting all scientific research as well as clinical and product intervention design and development.
Dr. Lyles previously served as a physician researcher and study director for multiple epidemiologic research initiatives in the Division of Infectious Diseases at the Cook County Health and Hospitals System, investigating healthcare-associated infections with a particular focus on the epidemiology and prevention of multidrug-resistant organisms and infections in intensive care units and in long-term acute care hospitals. She has directed numerous clinical studies and interventions for the Centers for Disease Control and Prevention (CDC) and the Chicago Antimicrobial Resistance and Infection Prevention Epicenter.
During her nine years as a study director and physician researcher at Hektoen Institute for Medical Research, Dr. Lyles’ work included CDC Epicenters Prevention program studies on bloodstream infections, Clostridium difficile infections and case-control studies of community-acquired Methicillin-resistant Staphylococcus aureus (MRSA). She also performed surveillance studies of Klebsiella pneumoniae carbapenemase (KPC) positive patients, examining universal contact isolation and patient skin antisepsis protocols to identify ways to optimize standard infection control measures.
Dr. Lyles received her medical degree from St. Matthew’s University School of Medicine and holds a Master of Health Service Administration from St. Joseph College. She also recently completed a Master of Science in Clinical Research and Translational Sciences through the University of Illinois at Chicago. She is an active member of the Association of Professionals in Infection Control and Epidemiology, the Infectious Disease Society of America, the Society for Healthcare Epidemiology of America and has served as a peer reviewer for the National Institutes of Health, New England Journal of Medicine, and American Journal of Infection Control.
References:
1. Dubberke, ER, et al. Strategies to Prevent Clostridium difficile Infections in Acute Care Hospitals: 2014 Update. Infect Control Hosp Epidemiol. 2014, V35:S48-S65
2. Tabak et al., Predicting the Risk for Hospital-onset Clostridium difficile Infection (HO-CDI) at the Time if Inpatient Admission: HO-CDI Risk Score. Infect Control Hosp Epidemiol. 2015, 36: 6; 695-701
3. Magill, SS. et al. “Multistate Point-Prevalence Survey of Health Care-Associated Infections.” The New England Journal of Medicine 370.13 (2014): 1198–1208.
4. Dubberke, ER, and Olsen, MA. “Burden of Clostridium Difficile on the Healthcare System.” Clinical infectious diseases 55 Suppl. 2 (2012): S88–92.
5. Septimus, E., et al. “Approaches for preventing Healthcare-associated Infections: Go Long or Go Wide?” Infect Control Hosp Epidemiol. 2014. 35: 7; 797-801