Capsule Fecal Transplant As Effective as By Colonoscopy for C. Diff Infections

MedicalResearch.com Interview with:

Clostridium difficile CDC image

Clostridium difficile
CDC image

Dina Kao, MD, FRCPC
Division of Gastroenterology, Department of Medicine
University of Alberta
Edmonton, Alberta, Canada

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We wanted to see what would be the best way to deliver fecal microbiota transplantation (FMT.)

There were many controlled studies of FMT delivered by various methods, showing different success rates. Not only were the route of delivery different, but the amount of donor stools also varied greatly from study to study. It appeared that most of the studies delivered by the upper routes gave a smaller amount of donor stool compared to the studies delivering FMT by colonoscopy.

Our hypothesis was that given the same amount of donor stool, the effectiveness would be similar by capsules and by colonsocopy.

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Hospital Onset Clostridium difficile Infections Increased With Electronic Sepsis Alerts

MedicalResearch.com Interview with:

Dr. Robert Hiensch MD Assistant Professor, Medicine, Pulmonary, Critical Care and Sleep Medicine Icahn School of Medicine at Mount Sinai

Dr. Hiensch

Dr. Robert Hiensch MD
Assistant Professor, Medicine, Pulmonary, Critical Care and Sleep Medicine
Icahn School of Medicine at Mount Sinai.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: New sepsis guidelines that recommend screening and early treatment for sepsis cases appear to have significant positive impacts on patient outcomes. Less research has been published on what potential side effects may result from these guidelines.

Antibiotics are a cornerstone of sepsis treatment and early antibiotic administration is strongly recommended.  We examined whether the introduction of an electronic based sepsis initiative changed antibiotic prescribing patterns at our hospital. Antibiotics, even when appropriate, contribute to hospital onset Clostridium difficile infections (HO CDIs).  While the authors do not dispute the importance of antibiotic administration in sepsis, it is valuable to know whether the sepsis initiative coincided with both increased antibiotic administration and HO CDIs.

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Antibiotics Prescribed By Dentists May Contribute To C.diff Infections

MedicalResearch.com Interview with:

Stacy Holzbauer, DVM, MPH, DACVPM CDC Career Epidemiology Field Officer (CEFO) Commander, USPHS Minnesota Department of Health St. Paul, MN

Dr. Holzbauer

Stacy Holzbauer, DVM, MPH, DACVPM
CDC Career Epidemiology Field Officer (CEFO)
Commander, USPHS
Minnesota Department of Health
St. Paul, MN

MedicalResearch.com: What is the background for this study?

  • Antibiotics are not harmless drugs—Clostridium difficile infection, which can sometimes cause a deadly diarrhea, is a complication of antibiotic use and can occur after even one dose of an antibiotic.
  • The Minnesota Department of Health (MDH) is part of the larger Centers for Disease Control and Prevention (CDC) Emerging Infections Program (EIP). The healthcare-associated infection component of CDC’s EIP engages a network of state health departments and their academic medical center partners to help answer critical questions about emerging HAI threats including Clostridium difficile also known as “C. diff.”
  • In Minnesota, the majority of C. diff infections occur outside the hospital and are driven by antibiotic use in community or outpatient settings. In addition to routine surveillance data, we interview patients with C. diff who were not hospitalized prior to their infection to identify potential risks for developing C. diff infection, including identifying antibiotics received outside of routine healthcare settings.
  • Dentists prescribe approximately 10% of the antibiotics in outpatient settings, which was over 24 million prescriptions in 2013. When asked about their prescribing practices in a 2015 survey with the Minnesota Dental Association, 36% of dentists surveyed prescribed antibiotics for dental conditions that are generally not recommended to receive antibiotics according to American Dental Association (ADA) guidelines.

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New Drug May Protect Gut From Antibiotic-Resistance Genes

MedicalResearch.com Interview with:

Synthetic Biologics, Inc.

Synthetic Biologics, Inc.

Sheila Connelly, PhD
Vice President, Research
Synthetic Biologics, Inc.

MedicalResearch.com: What is the background for this study?

Response: Synthetic Biologics, Inc. is focused on the protection and preservation of the gut microbiome which is the diverse collection of microorganisms that live in the intestinal tract. We are learning that the gut microbiome plays a key role in health. Negative changes to the microbiome, called dysbiosis, are linked to disease states including allergies, autism, and obesity, among a rapidly growing list of other conditions. A consequence of using antibiotics is that, in addition to fighting the bacterial infection being treated, they also kill the gut microbiota. The space left in the gut by the dead bacteria allows other surviving bacteria, many times opportunistic pathogens or microbes that are resistant to multiple antibiotics, to overgrow and fill the open niches. Exposure to antibiotics, particularly broad-spectrum antimicrobials, such as penicillins and cephalosporins, is a major risk factor for acquiring a potentially deadly Clostridium difficile infection.

Dr-Sheila-Connelly.jpg

Dr. Sheila Connelly

Another consequence of antibiotic use is the emergence of antibiotic-resistant organisms. Widespread use of antibiotics provides selective pressure for the evolution of lethal, multi-drug resistant pathogens, termed “nightmare bacteria”. The gut microbiome acts as a reservoir of antibiotic resistance that can be triggered, by antibiotic exposure, to acquire and propagate resistance genes.

A way to protect the microbiome and reduce antibiotic resistance is to limit exposure of the gut microbiota to antibiotics. To this end, we developed an antibiotic inactivation strategy using a beta-lactamase enzyme to degrade beta-lactam antibiotics in the GI tract before they can harm the gut microbiome. Beta-lactamases are naturally-occurring bacterial enzymes that confer resistance to beta-lactams, the most widely used broad spectrum antibiotics, and their presence is normally considered an obstacle to efficacious infection control. We took advantage of the highly efficient antibiotic degradation activity of a beta-lactamase and developed SYN-004 (ribaxamase). Ribaxamase is a beta-lactamase engineered to inactivate penicillins and most cephalosporins, formulated for oral delivery, and intended for use with IV beta-lactam antibiotics to degrade the antibiotics in the GI tract to protect the microbiome.

Ribaxamase was demonstrated to significantly reduce the occurrence of C. difficile disease in a recently completed Phase 2b clinical study. The study met its primary endpoint by demonstrating that ribaxamase, when delivered orally with IV ceftriaxone, significantly reduced C. difficile disease in patients treated for a respiratory tract infection. Ribaxamase also resulted in a significant reduction in new colonization by vancomycin-resistant enterococcus (VRE).

For the current study, pig models of antibiotic-mediated gut dysbiosis were established using three classes of beta-lactam antibiotics, a cephalosporin, ceftriaxone, a penicillin, amoxicillin, and a carbapenem, ertapenem. The ceftriaxone model was used to evaluate the protective effect of ribaxamase on the microbiome and the amoxicillin and ertapenem models are intended for evaluation of pipeline products.

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Patients With Clostridium difficile Infections Should Have Need For Gastric Acid Suppression Reassessed

MedicalResearch.com Interview with:

Sahil Khanna,

Dr. Sahil Khanna

Sahil Khanna, M.B.B.S. MS
Division of Gastroenterology and Hepatology
Mayo Clinic, Rochester, Minnesota

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea and has recently shown increasing incidence especially in the community. Novel risk factors for CDI development include the use of gastric acid suppression medication, presence of systemic comorbid conditions, C difficile carriage in water and food sources, amongst others.

Gastric acid suppression medications such as proton-pump inhibitors (PPIs) and histamine-2 receptor blockers (H2Bs) are commonly prescribed and consumed over the counter for gastroesophageal reflux disease, peptic ulcer disease, or functional dyspepsia, but they are also sometimes prescribed for unnecessary indications, which leads to overuse of these medications. Recurrent CDI after a primary infection is a major problem, with the risk being as high as 50% to 60% after 3 or more Clostridium difficile infections. Data on the association between acid suppression and recurrent CDI are conflicting and therefore we performed a systematic review and meta-analysis to study the association between the use of gastric acid suppression medications and the risk of recurrent CDI.

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Frozen Fecal Transplant in Pill Form Found To Reverse C. Diff Infection

MedicalResearch.com Interview with:

Dr. H. L. DuPont MD Director, Center for Infectious Diseases, UTHealth School of Public Health Mary W. Kelsey Chair in the Medical Sciences, McGovern Medical School at UTHealth Professor, Department of Epidemiology, Human Genetics and Environmental Sciences UTHealth School of Public Health Houston, TX 77030

Dr. DuPont

Dr. H. L. DuPont MD
Director, Center for Infectious Diseases, UTHealth School of Public Health
Mary W. Kelsey Chair in the Medical Sciences, McGovern Medical School at UTHealth
Professor, Department of Epidemiology, Human Genetics and Environmental Sciences
UTHealth School of Public Health
Houston, TX 77030

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Many diseases and disorders are associated with “dysbiosis,” where the intestinal microbiota diversity is reduced. This contributes to disease and to the acquisition of antibiotic resistance. Fecal microbiota transplantation (FMT) is successful in conditions with pure dysbiosis (e.g. C diff infection) and a single dose of FMT is curative in most cases.

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Severe Clostridium difficile Infections May Be Better Treated With Vancomycin

MedicalResearch.com Interview with:

Vanessa W. Stevens, PhD IDEAS 2.0 Center, Veterans Affairs (VA) Salt Lake City Health Care System Division of Epidemiology, Department of Internal Medicine University of Utah School of Medicine Salt Lake City, Utah

Dr. Vanessa Stevens

Vanessa W. Stevens, PhD
IDEAS 2.0 Center, Veterans Affairs (VA) Salt Lake City Health Care System
Division of Epidemiology, Department of Internal Medicine
University of Utah School of Medicine
Salt Lake City, Utah

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Although metronidazole remains the most commonly used drug to treat Clostridium difficile infection (CDI), there is mounting evidence that vancomycin is a better choice for some patients. Most previous studies have focused on primary clinical cure, but we were interested in downstream outcomes such as disease recurrence and mortality. We found that patients receiving metronidazole and vancomycin had similar rates of recurrence, but patients who were treated with vancomycin had lower risks of all-cause mortality. This was especially true among patients with severe Clostridium difficile.

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Fecal Microbiota Transfer Effective in Over 80% of Recurrent C. Diff Infection

MedicalResearch.com Interview with:
Yvette van Beurden
PhD student Gastroenterology & Hepatology / Medical Microbiology & Infection Control
VU University medical center
Amsterdam, the Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The use of fecal microbiota transfer (FMT), which is defined as the transfer of intestinal microbiota from healthy donors to patients, has gained momentum across the globe, since it was established as a highly effective method for treatment of recurrent Clostridium difficile infection (CDI), with cure rates around 85%. However, worldwide implementation of FMT is currently limited by a lack of uniform guidelines, concerns about safety, and remaining uncertainty of long-term side effects.

In our study, we reported the long-term follow up of patients treated with FMT for recurrent CDI.
With a primary cure rate of 82%, our study supports the currently available evidence that fecal microbiota transfer is a very effective treatment for recurrent CDI. Importantly, a first post-FMT recurrence of CDI can be successfully treated with antibiotics.

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Death Rate Higher In C.diff Patients Who Do Not Receive Guideline-Adherent Therapy

MedicalResearch.com Interview with:

Dr. Shannon Novosad, MD Epidemic Intelligence Service, CDC Division of Healthcare Quality Promotion National Center for Emerging and Zoonotic Infectious Diseases

Dr. Shannon Novosad

Dr. Shannon Novosad, MD
Epidemic Intelligence Service, CDC
Division of Healthcare Quality Promotion
National Center for Emerging and Zoonotic Infectious Diseases

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Clostridium difficile can cause an infection in the colon called colitis. Symptoms include diarrhea, fever, nausea, and abdominal pain. It is an important cause of healthcare associated infections with approximately half a million C. difficile infections and 29,000 associated deaths in 2011. The Infectious Diseases Society of America and Society for Healthcare Epidemiology of America published guidelines in 2010 advising clinicians on appropriate antibiotic regimens to treat C. difficile infection.  Prior studies have found that provider adherence to these guidelines, particularly in those with severe disease, is poor.  However, these studies primarily involved patients treated at a single healthcare facility. We were interested in examining CDI treatment practices in a larger group of patients with C. difficile infection located across geographically diverse areas. Further we wanted to learn more about what patient characteristics might be associated with receiving guideline-adherent therapy for C. difficile infection.

We used data from the Center for Disease Control and Prevention’s Emerging Infections Program (EIP) which performs active population and laboratory-based surveillance for C. difficile infections in 10 U.S. sites and examined how 11,717 patients including 2006 with severe disease were treated. We found that provider adherence to national treatment guidelines was low with only around 40% of those with severe disease being prescribed the appropriate antibiotic treatment. Our analysis suggests that those who were tested for C. difficile in the hospital or who were admitted to the hospital around the time of diagnosis were more likely to receive recommended antibiotic therapy.

In addition, patients greater than 65 years old or with more underlying comorbidities were more likely to receive the right antibiotic treatment. We also found that after adjusting for age and underlying comorbidities, the odds of death within 30 days of diagnosis was almost 400% higher in patients who did not receive guideline-adherent therapy compared to those who did.

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Antibiotics Encourage Spread of C.diff To Subsequent Patients Who Occupy the Same Bed and Haven’t Received Antibiotics

MedicalResearch.com Interview with:

Dr. Daniel E. Freedberg MD M

Dr. Daniel E. Freedberg

Dr. Daniel E. Freedberg MD MS
Division of Digestive and Liver Diseases
Columbia University Medical Center
New York, New York

MedicalResearch.com: What is the background for this study?

Response: We conducted this study because previous studies indicate that the gastrointestinal microbiome is easily shared between people who co-occupy a given space (such as a hospital room).  We wondered if antibiotics might exert an effect on the local microbial environment.

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Excess Zinc May Predispose to C.diff By Altering Gut Microbiome

MedicalResearch.com Interview with:

Eric P Skaar, Ph.D., MPH Director, Division of Molecular Pathogenesis Ernest W. Goodpasture Professor of Pathology Vice Chair for Basic Research, Department of Pathology, Microbiology, and Immunology Vanderbilt University School of Medicine

Dr. Eric P Skaar,

Eric P Skaar, Ph.D., MPH
Director, Division of Molecular Pathogenesis
Ernest W. Goodpasture Professor of Pathology
Vice Chair for Basic Research, Department of Pathology, Microbiology, and Immunology
Vanderbilt University School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Nutrient metals are known to be a critical driver of the outcome of host-pathogen interactions, and C. difficile is the most common cause of hospital-acquired infections. C. difficile infection typically occurs following antibiotic-mediated disruption of the healthy microbiome. We were interested in learning how nutrient metals can shape the microbiome and impact the outcome of Clostridium difficile infection.

We found that excess zinc alters the structure of the microbiome and increases the severity of C. difficile infection in mice.

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Genes That Enable C. diff Toxin Production Identified

MedicalResearch.com Interview with:

Charles Darkoh, Ph.D., MS., MSc. Assistant Professor University of Texas Health Science Center at Houston School of Public Health Department of Epidemiology, Human Genetics & Environmental Sciences Center for Infectious Diseases Houston, Texas 77030

Dr. Charles Darkoh

Charles Darkoh, Ph.D., MS., MSc.
Assistant Professor
University of Texas Health Science Center at Houston
School of Public Health
Department of Epidemiology, Human Genetics & Environmental Sciences
Center for Infectious Diseases
Houston, Texas 77030

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Clostridium difficile (Cdiff) is a multidrug-resistant pathogen that takes over the colon after the good bacteria in the colon have been wiped out by antibiotic therapy. As a result, antibiotic treatment is a major risk factor for C. diff infections. Because of the ability of C. diff to inactivate the majority of the antibiotics currently available, it has become necessary to urgently develop a non-antibiotic therapy for this life-threatening infection. We know that C. diff causes disease by producing toxins, designated toxin A and B. During infection, the toxins are released into the colon resulting in diarrhea and inflammation of the colon as well as other diarrhea-associated illnesses. We also know that C. diff strains that are unable to produce toxins cannot cause disease. Therefore, the toxins are promising targets for a non-antibiotic therapy.

We reported last year that C. difficile regulates toxin production using quorum sensing — a system that allows bacteria to coordinate their biological activities as a group. Two sets of quorum-sensing genes (agr1 and agr2) were identified. These genes form part of a signaling communication system that makes a small peptide, which serves as a cue for the infecting bacterial population to turn on their toxin genes.

In this study we used genetic analysis to identify which of these two sets of genes is responsible for regulating the toxins. Our results demonstrates that agr1 is the culprit. This is because Cdiff agr1 mutant cannot produce toxins and unable to cause disease in mice, whereas the agr2 mutant can cause disease just like the wild type C.diff.

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Probiotics Found Effective in Preventing Clostridium difficile in Hospitalized Adults Receiving Antibiotics

MedicalResearch.com Interview with:

Dr. Nicole Shen New York-Presbyterian/Weill Cornell Medical College

Dr. Nicole Shen

Dr. Nicole Shen
New York-Presbyterian/Weill Cornell Medical College

MedicalResearch.com: What is the background for this study?

Dr. Shen: Clostridium difficile infection (CDI) is a persistent, healthcare associated infection with significant morbidity and mortality that costs the US billions of dollars annually. Prevention is imperative, particularly for patients at high risk for infection – hospitalized adults taking antibiotics. Trials have suggested probiotics may be useful in preventing CDI. We conducted a systematic review with meta-analysis in this high-risk population, hospitalized adults receiving antibiotics, to evaluate the current evidence for probiotic use for prevention of CDI.

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Isolating Asymptomatic C. diff Carriers at Hospital Admission May Decrease Transmission

MedicalResearch.com Interview with:
Yves Longtin, MD, FRCPC
Chair, Infection Prevention and Control Unit
Montreal Jewish General Hospital – SMBD
Associate professor of Medicine, McGill University

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Longtin: Clostridium difficile is a major cause of infection in hospitalized patients. Current infection control measures to prevent the spread of C. difficile in hospitals focuses almost entirely on patients who present symptoms. Patients with symptoms of diarrhea due to C difficile are placed under isolation in hospitals (for example, healthcare workers will wear a gown and gloves when caring for them). However, many studies have shown that some patients may be asymptomatic carriers of C. difficile. These patients carry the C difficile bacteria in their digestive tract without being sick. It was known that these asymptomatic carriers could spread the bacteria to other patients, but it was unclear whether putting them into isolation would help prevent the spread of the microbe in hospitals. Our study tested the hypothesis that placing asymptomatic carriers under isolation could lead to a decrease in the number of infections with C  difficile.

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Antibiotic Induced Depletion of Bile Acids Facilitates Growth of C. diff

Casey M. Theriot, Ph.D. Assistant Professor Infectious Disease College of Veterinary Medicine Department of Population Health and Pathobiology North Carolina State University Raleigh, NC 27607

Dr. Casey Theriot

MedicalResearch.com Interview with:
Casey M. Theriot, Ph.D.
Assistant Professor Infectious Disease
College of Veterinary Medicine
Department of Population Health and Pathobiology
North Carolina State University
Raleigh, NC 27607

Medical Research: What is the background for this study? What are the main findings?

Dr. Theriot: This study is an extension of the work we did in 2014 in our Nature Communications paper (Theriot et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection, 2014). We really wanted to know how different antibiotics that varied in their mechanism of action altered the gut microbiota in different ways and also in turn how this altered the bile acids present in the small and large intestine of mice. Primary bile acids are made by the host and are further converted to secondary bile acids by members of the microbiota in the large intestine. We know from previous work that secondary bile acids can inhibit the growth of C. difficile, but no one has looked in depth at the bile acid makeup in the actual gut before in the context of C. difficile. In this study we show that specific antibiotics that significantly alter the large intestinal gut microbiota and deplete all secondary bile acids allow for C. difficile to grow without any inhibition. We also showed that C. difficile spores are always germinating in the small intestine, which means in order to prevent this pathogen from colonizing the gut, we will have to target the growth of the pathogen. Moving forward the focus will be on trying to repopulate the gut with bacteria that are capable of restoring the secondary bile acid pools in order to inhibit C. difficile.

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Three Factors Identify Risk of Fecal Transplant Failure for C. Diff Infections

Monika Fischer, MD, MSCR Assistant Professor of Clinical Medicine Division of Gastroenterology and Hepatology Indiana University Indianapolis, IN 46202

Dr. Monika Fischer

MedicalResearch.com Interview with:
Monika Fischer, MD, MSCR
Assistant Professor of Clinical Medicine
Division of Gastroenterology and Hepatology
Indiana University
Indianapolis, IN 46202 

Medical Research: What is the background for this study? What are the main findings?

Dr. Fischer: Cumulative evidence based upon case series and randomized trials suggest high success rate with 10-20 % failing a single FMT (fecal microbiota transplant). Predictors of failures are not known. In a collaborative study between Indiana and Brown Universities we aimed to identify clinical predictors of FMT failure.

Results were the following:

  • N= 345 patients
    • Brown: N=166
    • IU: N=179
  • Average age: 62 years
  • Females: 72%
  • IBD: 18%
  • Immunosuppression: 24%
  • Indication for FMT
    • Recurrent CDI: 74%
    • Refractory CDI: 26%
    • Severe/complicated CDI: 13%
  • Inpatient FMT: 17%
  • Patient directed donor: 40%

Overall failure rate was 23.7%. Broken down by fecal microbiota transplant indication, while only 18% of patients failed and  needed further therapy in the non-severe category, 1 in 2 (50%) severe C. difficile infection (CDI) patients failed a single fecal microbiota transplant and needed further therapy for cure.

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Microbiome Signature Can Predict Risk of C. difficile Treatment Failure

Dr. Sahil Khanna MBBS Assistant Professor of Medicine Mayo Clinic

Dr. Sahil Khanna

MedicalResearch.com Interview with:
Dr. Sahil Khanna MBBS
Assistant Professor of Medicine
Mayo Clinic

Medical Research: What is the background for this study? What are the main findings?

Response: C. difficile infection patients are at a high risk of complications such as treatment failure. Gut microbiota signatures associated with CDI have been described but it is unclear if differences in gut microbiota play a role in response to therapy. No studies have identified predictors of treatment failure and we aimed to identified gut microbiota signatures to predict response to treatment for primary C. difficile . While there were no clinical predictors of treatment response, there were increases in certain genera in patients with successful treatment response in the fecal samples at initial diagnosis compared to non-responders. A risk index built from this panel of microbes highly differentiated between patients based on response and ROC curve analysis showed that this risk index was a strong predictor of treatment response, with a high area under the curve of 0.83..

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Molecular Test For C. difficile Leads To Overdiagnosis

Christopher R. Polage, M. D. Associate Professor of Pathology and Infectious Diseases University of California, Davis School of Medicine Medical Director, Microbiology Laboratory and SARC UC Davis Health System

MedicalResearch.com Interview with:
Christopher R. Polage, M. D.
Associate Professor of Pathology and Infectious Diseases
University of California, Davis School of Medicine
Medical Director, Microbiology Laboratory and SARC
UC Davis Health System

 


Medical Research: What is the background for this study?

Dr. Polage: Clostridium difficile is a frequent cause of diarrhea and infection in U.S. hospitals but common diagnostic tests often disagree about which patients are infected or need treatment. We compared clinical symptoms and outcomes in hospitalized patients with different C. difficile test results to determine which type of test (molecular or PCR test versus toxin test) was the better predictor of need for treatment and disease.

Medical Research: What are the main findings?

Dr. Polage: Twice as many patients were positive by the molecular test versus the conventional toxin test. However, patients with a positive molecular test only had a shorter duration of symptoms than patients with toxins, and outcomes that were similar to patients withoutC. difficile by all test methods. Virtually all traditional complications of C. difficile infection occurred in patients with a positive toxin test; none occurred in patients with a positive molecular test only, despite little or no treatment.

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Single Use Sharps Recycling Many Reduce C. diff Infections

Dr. Monika Pogorzelska-Maziarz PhD MPH Thomas Jefferson University, Jefferson School of Nursing Philadelphia, PA 19107MedicalResearch.com Interview with:
Dr. Monika Pogorzelska-Maziarz PhD MPH

Thomas Jefferson University, Jefferson School of Nursing
Philadelphia, PA 19107

Medical Research: What is the background for this study? What are the main findings?


Dr.
Pogorzelska-Maziarz: Sharps disposal containers are ubiquitous in healthcare facilities and there is a growing trend toward hospitals using reusable sharps containers. Several research studies have raised concerns about the potential for sharps containers to become a source of pathogen transmission within the healthcare setting but this issue that has not been systematically studied. This is an important issue given that contamination of the hospital environment has been shown to be an important component of pathogen transmission.

To examine whether the use of reusable versus single use sharps containers was associated with rates of Clostridium difficile, we conducted a cross-sectional study of acute care hospitals. Survey data on the different types of sharps containers used were collected from over 600 hospitals and this data was linked to the Medicare Provider Analysis and Review (MedPAR) dataset, which contains facility characteristics and C. diff infections data. We found that hospitals using single-use containers had significantly lower rates of C. diff versus hospitals using reusable containers after controlling for hospital characteristics such as geographic region, teaching status, ownership type, hospital size and urbanicity. This is an important finding giving the ubiquitous nature of sharps containers in the health care setting, the growing trend toward hospitals using reusable sharps containers and the high burden of C. diff in the hospital setting. Continue reading

Acid-Suppression Medications Linked To Increased Pediatric C. diff Infections

Daniel E. Freedberg, MD, MS Assistant Professor of Medicine Division of Digestive and Liver Diseases Columbia University, New YorkMedicalResearch.com Interview with:
Daniel E. Freedberg, MD, MS

Assistant Professor of Medicine
Division of Digestive and Liver Diseases
Columbia University, New York

Medical Research: What is the background for this study?

Dr. Freedberg: Acid suppression medications are increasingly prescribed to relatively healthy children without clear indications, but the side effects of these medications are uncertain.


Medical Research: What are the main findings?

Dr. Freedberg: Acid suppression with (proton pump inhibitors ) PPIs or (histamine-2 receptor antagonists) H2RAs was associated with increased risk for C. diff infection in both infants and older children.

Medical Research: What should clinicians and patients take away from your report?

Dr. Freedberg: Increased risk for C. diff should be factored into the decision to use acid suppression medications in children.  Our findings imply that acid suppression medications alter the bacterial composition of the lower gastrointestinal tract.

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Non-Toxic Spores May Prevent C. difficile infection

Dale N. Gerding, MD Research Physician, Edward Hines, Jr., VA Hospital Professor, Department of Medicine of Loyola University Chicago Stritch School of MedicineMedicalResearch.com Interview with:
Dale N. Gerding, MD
Research Physician, Edward Hines, Jr., VA Hospital
Professor, Department of Medicine of Loyola University Chicago Stritch School of Medicine

Medical Research: What is the background for this study? What are the main findings?

Dr. Gerding: Naturally occurring strains of C. difficile lack the genes for production of the toxins that cause C. difficile infection (CDI) and are known as non-toxigenic C. difficile (NTCD). These strains when ingested by patients whose normal microbiota is disrupted by antibiotic treatment will harmlessly colonize the colon and remain in the gut for weeks to months. Specific strains of NTCD found in patients were shown to colonize the gut and prevent C. difficile infection when challenged with toxigenic C. difficile strains in animal models. One such NTCD strain, NTCD-M3, was shown to be safe and well tolerated in human volunteer trials and was used in the present study to determine if it would prevent recurrence of C. difficile infection in patients who had just completed treatment with vancomycin or metronidazole of either their first CDI episode or first recurrence of
C. difficile infection. 168 patients were randomized to receive by mouth in a liquid form, either 10,000 spores/day of NTCD-M3 for 7 days, 10 million spores/day for 7 days, 10 million spores/day for 14 days, or an identical placebo for 14 days.  Primary outcome was safety, and secondary outcomes were the percent who colonized the gut with NTCD-M3 in the time period from end of treatment to week 6, and the rate of recurrent CDI in the patients at week 6. The results showed that NTCD-M3 was safe and well tolerated, and colonized the gut of 69% of patients who received it. The C. difficile infection recurrence rate was 30% in the placebo patients and 11% in patients who received any of the NTCD-M3 doses (P<.006). The best dose tested was 10 million spores/day for 7 days which resulted in a recurrence rate of only 5% (p<.01 vs placebo). Colonization of the gut was not permanent, but lasted a maximum of 22 weeks. The summary conclusion is that NTCD-M3 is safe, colonized the gut, and when it colonized the gut, reduced recurrence of C. difficile infection to 2% (p<.001 vs patients who were not colonized).

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Fecal Microbiota Transplantation May Normalize Intestinal Microbiome

Michael J Sadowsky Ph.D Director, BioTechnology Institute University of MinnesotaMedicalResearch.com Interview with:
Michael J Sadowsky Ph.D
Director, BioTechnology Institute
University of Minnesota
MedicalResearch: What is the background for this study? What are the main findings?

Dr. Sadowsky: Fecal microbiota transplantation (FMT) has become increasingly common in the treatment of patients with refractory Clostridium difficile infection (CDI). It also holds promise for the treatment of medical conditions ranging from inflammatory bowel and Crohn’s disease to diabetes and metabolic syndrome. In contrast to standard antibiotic therapies, which further disrupt intestinal microflora and may contribute to the recurrence of CDI, FMT restores intestinal microbiome and healthy gut function.

Despite therapeutic successes, little is known about the stability of transplanted microbiota over time. This report contributes to our understanding of the short-and long-term composition of gut microbiota following Fecal microbiota transplantation.

In this study, fecal samples collected before and after treatment were compared with data from the Human Microbiome Project (HMP). Treatment using FMT resulted in the rapid normalization of microbial composition in the patient, with the post-treatment profiles closely resembling the normal distribution of fecal microbiota from the donor. While the composition of fecal microbiota in the donor and recipient varied over time, both remained in the large band characterized as normal in hundreds of healthy individuals collected as part of the HMP. Furthermore, while the composition of the microflora in Fecal microbiota transplantation recipients and donors diverges over time, the recipient profiles stay within the same dynamic range as the original implanted donor material.

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C. difficile Most Common Health Care Associated Infection

Fernanda C. Lessa, M.D., M.P.H. Centers for Disease Control and Prevention Atlanta, GAMedicalResearch.com Interview with:
Fernanda C. Lessa, M.D., M.P.H.
Centers for Disease Control and Prevention
Atlanta, GA

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Lessa: The epidemiology of Clostridium difficile has gone through dramatic changes over the last decade. C. difficile has become the most common cause of healthcare-associated infections in US hospitals and it has been also increasingly reported outside of healthcare settings. As the epidemiology of this pathogen changes, it is important to understand the magnitude and scope of this infection in the United States to help guide priorities for prevention.

Main findings:

1)      C. difficile was responsible for almost half million infections and associated with 29,000 deaths in 2011 in the United States

2)      Among the patients who developed C. difficile, 83,000 had recurrent infections

3)      C. difficile incidence was higher among females, whites, and persons 65 years of age or older

4)       Approximately 345,400 infections occurred outside of the hospital indicating that C. difficile prevention should go beyond hospital settings.

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Proton Pump Inhibitors May Decrease Gut Diversity, Increase C. diff Risk

Dr. John K. DiBaise MD Gastroenterology and Hepatology Mayo Clinic, Scottsdale ArizonaMedicalResearch.com Interview with:
Dr. John K. DiBaise MD
Gastroenterology and Hepatology
Mayo Clinic, Scottsdale Arizona

Medical Research: What is the background for this study? What are the main findings?

Dr. DiBaise: Despite nearly 25 years of safe and effective use of proton pump inhibitors (PPI), in recent years there have been an increasing number of reports suggesting potentially harmful effects and harmful associations with their use.  One such association with PPI use has been Clostridium difficile infection (CDI) which can cause severe and recurrent episodes of diarrhea.  Previous reports evaluating the microbes present within the gastrointestinal tract (ie, gut microbiome) of individuals with CDI have shown a reduction in overall microbial community diversity.  We studied the gut microbiome in healthy individuals both before and after using a proton pump inhibitors for one month and found a similar reduction in microbial diversity while taking the PPI that did not entirely revert back to the ‘normal’ baseline after being off the medication for a month.  While this does not demonstrate a causal association between proton pump inhibitors use and CDI, it demonstrates that PPI use creates a situation in the gut microbial environment that may increase the individual’s susceptibility to CDI.

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Resistant C. Diff Infections Treatable With Pill Form of Fecal Bacterial Transplant

Dr.  Ilan Youngster, MD, MMSc Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Division of Infectious Diseases, Boston Children’s Hospital Boston, MassachusettMedicalResearch.com Interview with:
Dr.  Ilan Youngster, MD, MMSc
Division of Infectious Diseases, Massachusetts General Hospital,
Harvard Medical School,
Division of Infectious Diseases, Boston Children’s Hospital
Boston, Massachusetts

Medical Research: What are the main findings of the study?

Dr. Youngster: The main finding is that oral administration seems to be as safe and effective as more traditional routes of delivery like colonoscopy or nasogastric tube. This is important as it allows Fecal microbiota transplantation (FMT) to be performed without the need of invasive procedures, making it safer, cheaper and more accessible to patients.

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Hospital Acquired C. diff Infections Increase Both Length of Stay and Mortality

MedicalResearch.com Interview with:
Esther van Kleef
London School of Hygiene and Tropical Medicine,
London, UK

Medical Research: What are the main findings of the study?

Response:  Existing evidence reveals a wide variation in estimated excess length of hospital stay (LoS) associated with healthcare-acquired C. difficile infection (HA-CDI), ranging from 2.8 to 16.1 days. Few studies considered the time-dependent nature of healthcare-acquired C. difficile (i.e. patients that spent a longer time in hospital have an increased risk of infection), and none have considered the impact of severity of healthcare-acquired C. difficile on expected delayed discharge. Using a method that adjusted for this so-called time-dependent bias, we found that compared to non-infected patients, the excess length of stay of severe patients (defined by increased white blood cell count, serum creatinine, or temperature, or presence of colitis) was on average, twice (11.6 days; 95% CI: 3.6-19.6) that of non-severe cases (5.3 days; 95% CI: 1.1-9.5). However, severely infected patients did not have a higher daily risk of in-hospital death than non-severe patients. Overall, we estimated that healthcare-acquired C. difficile prolonged hospital stay with an average of ~7 days (95% CI: 3.5-10.9) and increased in-hospital daily death rate with 75% (Hazard Ratio (HR): 1.75; 95% CI: 1. 16 – 2.62).

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Clostridium difficile Infections In US Hospitals Doubled over Decade

Kelly R. Reveles, PharmD, PhD The University of Texas College of PharmacyMedicalResearch.com Interview with:
Kelly R. Reveles, PharmD, PhD
The University of Texas College of Pharmacy

Medical Research: What are the main findings of the study?

Dr. Reveles: Our study utilized data from the Centers for Disease Control and Prevention’s National Hospital Discharge Surveys. Patients were selected for this study if they were at least 18 years of age and had an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code for Clostridium difficile infection (CDI) (ICD-9-CM code 008.45). We found that Clostridium difficile infection incidence increased from 4.5 CDI discharges/1,000 total discharges in 2001 to 8.2 CDI discharges/1,000 total discharges in 2010. Mortality varied over the study period with peak mortality occurring in 2003 (8.7%) and the lowest rate occurring in 2009 (5.6%). Median hospital length of stay (LOS) was 8 days and remained stable over the study period. In summary, the incidence of Clostridium difficile infection in U.S. hospitals nearly doubled from 2001 to 2010, with little evidence of recent decline. Additionally, there does not appear to be a significant decline in mortality or hospital LOS among patients with Clostridium difficile infection.

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C. difficile: Novel Gene Detection Method

Stephanie Angione PhD Candidate Brown University School of Engineering Center for Biomedical EngineeringMedicalResearch.com Interview with:
Stephanie Angione
PhD Candidate
Brown University School of Engineering
Center for Biomedical Engineering

MedicalResearch.com: What are the main findings of the study?

Answer: This study demonstrates the application of a novel nucleic acid detection platform to detect Clostridium difficile (C. difficile) in subjects presenting with acute diarrheal symptoms. This method amplifies three genes associated with C. difficile infection as well as genes associated with virulence attributed to the NAP1/027/BI strain. The novel PCR assay allows for simple and rapid detection of three C. difficile genes: tcdB, cdtB, and tcdC, which code for C. difficile toxin B, C. difficile binary toxin, and a protein suspected to regulate toxin production, which includes the NAP1/027/BI tcdC variant. Amplification of DNA from the tcdB, tcdC and cdtB genes can be carried out using a droplet sandwich platform that performs real-time polymerase chain reaction (PCR) in microliter droplets for the detection and identification of amplified fragments of DNA. Our technique of multiplex gene amplification provides a unique method that is both sensitive and specific to rapidly detect C. difficile in patient stool samples that can be adapted to point-of-care testing. Continue reading

C.diff and Obesity

MedicalResearch.com Interview with:
Nahid Bhadelia, MD, MALD
Assistant Professor
Associate Hospital Epidemiologist, Section of Infectious Diseases
Director, Infection Control
National Emerging Infectious Diseases Laboratory (NEIDL)
Boston Medical Center, Boston, MA

Summary of Findings:
Dr.
Bhadelia:

Clostridium difficile infections (CDI) are a growing problem related to healthcare exposure and antibiotic use. Over the last decade, these infections have been noted to present in patients from the community without traditional risk factors. We examined 132 patients over a six month period presenting to our medical center with CDI to explore the association between obesity and CDI. We hypothesized that in a group without exposure to health care facilities, the statistical significance of other risk factors such as obesity and IBD may be increased. Our results showed that patients with community onset CDI without known health exposure were 4 times more likely to be obese than their counterparts (OR, 4.06 95% CI 1.15–14.36) with known healthcare exposure. Furthermore, this former group was also statistically more obese than the general population of Massachusetts (34% vs 23%, OR 1.7, 95% CI 1.02–2.99).

We did not note a similar difference between community onset patients without healthcare exposure and patients who developed CDI in the hospital. This may be due to limitations of sample size or because obesity maybe a confounder in hospitalized patients and a marker for other conditions requiring admission.

Obesity has not previously been considered a risk factor for CDI but given the similarities in the derangement of gut microbiome in obese patients and that of patients with inflammatory bowel disease and recurrent antibiotic use, there is biological plausibility for this finding. Further prospective and translational research is required to elucidate the pathogenesis behind this observation. These findings may contribute to improved clinical surveillance of those at highest risk of disease.

Citation:

Possible Association between Obesity and Clostridium difficile Infection

Decline in C. Difficile may be due to Decreased Antibiotic Exposure

MedicalResearch.com Interview with:
David W. Eyre, B.M., B.Ch.
Nuffield Department of Clinical Medicine
University of Oxford
National Institute for Health Research (NIHR) Oxford Biomedical Research Centre
John Radcliffe Hospital

MedicalResearch.com: What are the main findings of this study?

Dr. Eyre: All cases of Clostridium difficile in Oxfordshire were studied over 3 years. Isolates were characterized by whole genome sequencing and the data was linked to hospital databases allowing epidemiological relationships between patients at the level of the hospital ward, hospital specialty, and post code to be identified. For comparison, similar information was also available for all other patients with and without diarrhea.  Preliminary work on the genetic diversity of Clostridium difficile within individuals and between individuals within discrete outbreaks allowed reliable interpretation of transmission events using genomic data.

This allowed a complete reconstruction of the pattern of transmission between affected cases in Oxfordshire to be made.

The findings were:
1. Unexpectedly few cases (13%) appear to be acquired from direct ward based contact with other symptomatic cases (these have previously been thought to be the main source of infections, and the focus of prevention efforts). Another 6% were associated with other hospital contact and 3% had plausible community contacts.

2. In 13% of cases potential donors were identified gnomically but no contact, within hospitals or the community, were identified. This suggests that the existence of other modes of transmission of Clostridium difficile.

3. The sources of Clostridium difficile infections were highly genetically diverse, with 45% of cases having a genetically distinct origin – suggesting a diverse reservoir of disease, not previously appreciated

4. During the 3 years of the study the rate of Clostridium difficile in Oxfordshire fell.  Any improvement in infection control techniques would be expected to reduce the incidence of cases caused by within hospital transmission. Surprisingly, similar rates of fall occurred in both in secondary cases (considered to be acquired from hospital associated symptomatic cases) and for primary cases (cases not associated with transmission from symptomatic cases).
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Probiotics for the prevention of antibiotic-associated diarrhea and C.diff among hospitalized patients

MedicalResearch.com eInterview with: Dr. Reena Pattani MD
Department of Medicine
St. Michael’s Hospital
30 Bond Street, Toronto ON M5B 1W8

MedicalResearch.com: What are the main findings of the study?

Dr. Pattani: We performed a meta-analysis of 16 studies that assessed the effectiveness of probiotics administered concurrently with antibiotics compared to the use of antibiotics alone. The use of probiotics among patients in these trials reduced the risk of antibiotic-associated diarrhea by almost 40% and decreased the rate of Clostridium difficile infection by 63%. On subgroup analysis, the reduction remained statistically significant for the subgroups of good quality trials, trials in which a primarily Lactobacillus-based regimen was used, and those studies which had a follow-up period of less than 4 weeks.
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BI C. difficile strain found common in Chicago hospitals

An outbreak strain of Clostridium difficile, a bacterium that causes diarrhea and sometimes life-threatening inflammation of the colon, is common in Chicago-area acute care hospitals, an investigation published in the September issue of Infection Control and Hospital Epidemiology suggests.

In response to Illinois Department of Public Health reports of rising rates of C. difficile infection as a hospital discharge diagnosis, the Chicago and Cook County health departments surveyed 25 Chicago-area hospitals over one month in 2009. They identified 263 total cases of C. difficile illness. Of 129 C. difficile isolates cultured from these patients, 61 percent were the outbreak C. difficile strain known as BI/NAP1.

The BI strain, which is known to cause more serious illness, is usually associated with large acute outbreaks of C. difficile. However this investigation suggests that BI is endemic in the Chicago area and patients could be at risk for severe disease even in the absence of a large acute outbreak.

“Our findings highlight the need for effective interventions aimed at reducing the risk of C. difficile infection,” said Stephanie Black, MD with the Chicago Department of Public Health and the investigation’s lead author.

The investigation suggests that the transfer of patients from one facility to another has helped to spread the BI strain. Dr. Black and her team found that half of the patients with the BI strain were transferred from one healthcare facility to another. “Inter-facility transfer of recently infected patients is a plausible mechanism for the spread of the BI group and may explain in part how BI became the dominant [strain] in this region,” the authors write.

C. difficile is most common in elderly patients and those receiving treatment with antibiotics. It is considered to be one of the most important health care-related infections in the U.S.

The Society for Healthcare Epidemiology of America recommends that patients take the following steps to reduce the spread of C. difficile:

  • Make sure that all doctors, nurses, and other healthcare providers clean their hands with soap and water.
  • Only take antibiotics as prescribed by your doctor.
  • Be sure to clean your own hands often, especially after using the bathroom and before eating.
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Stephanie R. Black, Kingsley N. Weaver, Roderick C. Jones, Kathleen A. Ritger, Laurica A. Petrella, Susan P. Sambol, Michael Vernon, Stephanie Burton, Sylvia Garcia-Houchins, Stephen G. Weber, Mary Alice Lavin, Dale Gerding, Stuart Johnson, Susan I. Gerber, “Clostridium difficile Outbreak Strain BI Is Highly Endemic in Chicago Area Hospitals.” Infection Control and Hospital Epidemiology 32:9 (September 2011)