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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