Author Interviews, C. difficile, Gastrointestinal Disease, Imperial College, Infections, Transplantation / 30.04.2020

MedicalResearch.com Interview with: [caption id="attachment_54022" align="alignleft" width="149"]Prof. Julian Marchesi Prof. Marchesi[/caption] Prof. Julian Marchesi PhD Professor of Digestive Health Faculty of Medicine, Department of Metabolism, Digestion and Reproduction   [caption id="attachment_54021" align="alignleft" width="149"]Dr.-Benjamin-Mullish Prof. Mullish[/caption] Dr. Benjamin Mullish PhD Faculty of Medicine, Department of Metabolism, Digestion and Reproduction NIHR Clinical Lecturer Imperial College London       MedicalResearch.com: What is the background for this study? Response: Many patients are colonized with bacteria that are resistant to nearly all the antibiotics that we currently have. This antibiotic resistance is a huge public health problem, not least because it may lead to the scenario where a bacterial species moves from the gut and into the bloodstream, causes an infection, and cannot be treated. Such scenarios particularly occur in patients who are particularly prone to getting multiple and frequent courses of antibiotics; this may include patients with particular kidney conditions (who may be vulnerable to recurrent urinary tract infections (UTIs)), and patients with blood cancers (such as leukaemia, who have weak immune systems and are therefore prone to infections). Furthermore, in both sets of patients, to help treat their disease, they may be offered transplants, either a new kidney or new bone marrow. When this transplant happens, the clinician needs to ‘switch off’ their immune system to allow the transplant to work. When the immune system is dialled down, it can no longer stop any invading bacteria, increasing the chance of antibiotic resistance bacteria causing infections, which frequently leads to patient death. 
Author Interviews, C. difficile, Health Care Systems, Hospital Acquired, JAMA / 06.02.2020

MedicalResearch.com Interview with: [caption id="attachment_53096" align="alignleft" width="125"]Valerie Vaughn MD, MSc Assistant Professor of Medicine; Hospital Medicine VA Ann Arbor Healthcare System and University of Michigan Medical School @ValerieVaughnMD Dr. Vaughn[/caption] Valerie Vaughn MD, MSc Assistant Professor of Medicine; Hospital Medicine VA Ann Arbor Healthcare System and University of Michigan Medical School @ValerieVaughnMD MedicalResearch.com: What is the background for this study? Response: Health care-associated infection are a major patient safety problem. Fortunately, they can often be prevented through key practices. The Department of Veterans Affairs has been an early adopters of these key strategies through a combination of policies, directives, and initiatives which have aimed to reduce health care-associated infection. No one had previously looked across infections to see whether key infection prevention practices are being used in the VA.
Author Interviews, C. difficile, Hospital Acquired / 08.01.2020

MedicalResearch.com Interview with: [caption id="attachment_52674" align="alignleft" width="133"]Alexandre R. Marra, MD PhD Iowa Infection Prevention Research Group University of Iowa Carver College of Medicine Dr. Marra[/caption] Alexandre R. Marra, MD PhD Iowa Infection Prevention Research Group University of Iowa Carver College of Medicine Division of Medical Practice, Hospital Israelita Albert Einstein São Paulo, Brazil MedicalResearch.com: What is the background for this study? Response: This is a comprehensive systematic literature review evaluating the burden of C. difficile infections in the U.S healthcare system. The literature has diverse studies with variable outcomes. Thus, we only included incidence estimates derived from multicenter studies. In our meta-analysis to calculate incidence, data were pooled only with denominators using the same unit (patient-days) to avoid comparisons with different denominators. For length of stay (LOS), we only included studies that used advanced statistical methods (e.g., propensity score matching).
Author Interviews, C. difficile, Gastrointestinal Disease / 20.12.2019

MedicalResearch.com Interview with: [caption id="attachment_52518" align="alignleft" width="125"]Sarah W. Baron, M.D Assistant Professor Division of Hospital Medicine Department of Medicine, Montefiore Medical Center Bronx, New York Dr. Baron[/caption] Sarah W. Baron, M.D Assistant Professor Division of Hospital Medicine Department of Medicine, Montefiore Medical Center Bronx, New York  MedicalResearch.com: What is the background for this study? Response: We know that C. difficile can be a deadly and highly infectious disease but that it has been difficult to control. We also know that some people carry C. difficile in their body without symptoms but can still spread the organism or become sick with it themselves at some point in the future. This study attempted to answer two main questions: 1. First, how many patients coming into a large, urban academic medical center carried the organism C. difficile without any symptoms and 2. How many of those carriers without symptoms then went on to have the symptoms of C. difficile within 6 months?
Allergies, Author Interviews, C. difficile, Dental Research, Infections / 05.10.2019

MedicalResearch.com Interview with: [caption id="attachment_51763" align="alignleft" width="157"]Alan E. Gross, PharmD Clinical Assistant Professor University of Illinois Chicago, IL Dr. Gross[/caption] Alan E. Gross, PharmD Clinical Assistant Professor University of Illinois Chicago, IL MedicalResearch.com: What is the background for this study? Response: Dentists prescribe 10% of all outpatient antibiotics. Most of this prescribing is for infection prophylaxis prior to dental procedures. Our prior research has found that 80% of prescriptions for dental prophylaxis is unnecessary. Although antibiotic prophylaxis prior to dental procedures is often for a short course (e.g. one time amoxicillin dose), there may be patient harm associated with this.
Author Interviews, C. difficile, Pediatrics / 07.08.2019

MedicalResearch.com Interview with: [caption id="attachment_50595" align="alignleft" width="160"]Larry K. Kociolek, MD MSCI  Attending Physician, Division of Infectious Diseases, Associate Medical Director of Infection Prevention and Control, Ann & Robert H. Lurie Children’s Hospital of Chicago  Assistant Professor of Pediatrics Northwestern University Feinberg School of Medicine Dr. Kociolek[/caption] Larry K. Kociolek, MD MSCI Attending Physician, Division of Infectious Diseases, Associate Medical Director of Infection Prevention and Control, Ann & Robert H. Lurie Children’s Hospital of Chicago Assistant Professor of Pediatrics Northwestern University Feinberg School of Medicine  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clostridioides (Clostridium) difficile colonization is very common among infants, yet infants almost never develop symptoms of infection. In adults, it is known that immunity against the toxins that C. difficile produces protect against C. difficile infection (CDI). Our goal was to determine whether or not infants who become colonized with C. difficile develop an immune response against these toxins. We collected stool from healthy infants at multiple time points during the first year of life to determine whether or not they became colonized with C. difficile. Then at 9-12 months old, we collected blood to see if we can identify antibodies in their blood that protect against these toxins. We discovered that colonization with C. difficile during infancy was strongly associated with the development of antibodies. These antibodies were able to protect against the harmful effects of these toxins in a laboratory cell culture model.
Author Interviews, C. difficile, Gastrointestinal Disease, Johns Hopkins, Lipids / 09.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49043" align="alignleft" width="178"]Rajesh Kumar NV, Ph.D.Affiliation during the study:Senior Manager, Human Therapeutics Division,Intrexon Corporation, Germantown, MD, USA Dr. Rajesh Kumar NV[/caption] Rajesh Kumar NV, Ph.D. Affiliation during the study: Senior Manager, Human Therapeutics Division, Intrexon Corporation, Germantown, MD, USA Current affiliation: Translational Research Program Manager, Oncology Drug Discovery, Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine Baltimore, MD,   MedicalResearch.com: What is the background for this study? Response: Clostridium difficile is a bacterium that can cause symptoms ranging from diarrhea to life-threatening inflammation of the colon. Clostridium difficile infection is the most frequent form of colitis in hospitals and nursing homes and affects millions of patients in the United States and abroad. Clostridium difficile associated disease (CDAD) is a global public health challenge where even mild to moderate infections at times can quickly progress to a fatal disease if not treated promptly. OG253 is a novel lantibiotic in development for the treatment of CDAD. Lantibiotics are antimicrobial peptides whose chemical structure includes a bridge maintained by the non-canonical amino acid lanthionine. The primary objective of our study was to evaluate the repeated dose toxicokinetics and any possible side effects of OG253 as enteric-coated capsules following daily oral administrations of three different doses (6.75, 27 and 108 mg/day) for a single day or seven consecutive days in both genders of rats. An enteric-coated capsule of OG253 was formulated in an attempt to circumvent the proteolytic degradation of OG253 in the upper digestive tract and specifically deliver this lantibiotic to the distal portion of the small intestine.
Author Interviews, C. difficile, Microbiome, Pain Research / 09.01.2019

MedicalResearch.com Interview with: [caption id="attachment_46859" align="alignleft" width="133"]MedicalResearch.com Interview with: David M. Aronoff, MD, FIDSA, FAAM Professor & Addison B. Scoville Jr. Chair in Medicine Director, Division of Infectious Diseases Department of Medicine Vanderbilt University Medical Center MedicalResearch.com: What is the background for this study? Response: Clostridium difficile infection (CDI) is a major cause of antibiotic-associated colitis and diarrhea and a leading cause of hospital-acquired infection. It is caused by the toxin-producing, anaerobic, spore-forming bacterium Clostridium difficile. Antibiotic use is a major risk factor for CDI but epidemiological studies suggest that other factors, some modifiable, some not, can also increase the risk for CDI. Older age is an example of a non-modifiable risk factor for CDI. Some epidemiological studies suggested that taking the prostaglandin synthesis inhibiting drugs called non-steroidal anti-inflammatory drugs (NSAIDs) might also increase the risk for CDI. NSAIDs include medications such as ibuprofen, naproxen, indomethacin, and others. Because NSAID use is so common, if it is a risk factor for the acquisition of, or severity of, CDI, that would be important because that would be a modifiable risk factor. We therefore sought to determine the impact of NSAID exposure on CDI severity in a mouse model of antibiotic-associated CDI. We also sought evidence for possible mechanisms whereby NSAIDs might increase the risk for CDI. MedicalResearch.com: What are the main findings? Response: Exposure of mice to indomethacin (an NSAID) for two days prior to infection with Clostridium difficile in antibiotic-exposed mice increased the severity of disease and this was associated with severe inflammation, changes to the bacterial populations in the colon and increased damage to the protective epithelial lining of the colon. MedicalResearch.com: What should readers take away from your report? Response: Our studies provide evidence in a mouse model of CDI that support human epidemiological studies linking NSAID use with CDI. MedicalResearch.com: What recommendations do you have for future research as a result of this work? Response: Studies in humans are needed to see if NSAID use is indeed a causal risk factor for CDI acquisition or severity. MedicalResearch.com: Is there anything else you would like to add? Response: This work was funded by the National Institutes of Health and the Crohn’s and Colitis Foundation of America. Dr. Aronoff has served as Consultant for Synthetic Biologics, Inc, Biocidium, NAEJA-RGM and BLC-USA on projects unrelated to this study. He also has research funding from Pfizer unrelated to this study. Citation: Damian Maseda, Joseph P. Zackular, Bruno Trindade, Leslie Kirk, Jennifer Lising Roxas, Lisa M. Rogers, Mary K. Washington, Liping Du, Tatsuki Koyama, V. K. Viswanathan, Gayatri Vedantam, Patrick D. Schloss, Leslie J. Crofford, Eric P. Skaar, David M. Aronoff. Nonsteroidal Anti-inflammatory Drugs Alter the Microbiota and Exacerbate Clostridium difficile Colitis while Dysregulating the Inflammatory Response. mBio, 2019; 10 (1) DOI: 10.1128/mBio.02282-18 [wysija_form id="3"] [last-modified] The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website. Dr. Aronoff[/caption]David M. Aronoff, MD, FIDSA, FAAM Professor & Addison B. Scoville Jr. Chair in Medicine Director, Division of Infectious Diseases Department of Medicine Vanderbilt University Medical Center MedicalResearch.com: What is the background for this study? Response: Clostridium difficile infection (CDI) is a major cause of antibiotic-associated colitis and diarrhea and a leading cause of hospital-acquired infection. It is caused by the toxin-producing, anaerobic, spore-forming bacterium Clostridium difficile. Antibiotic use is a major risk factor for CDI but epidemiological studies suggest that other factors, some modifiable, some not, can also increase the risk for CDI. Older age is an example of a non-modifiable risk factor for CDI. Some epidemiological studies suggested that taking the prostaglandin synthesis inhibiting drugs called non-steroidal anti-inflammatory drugs (NSAIDs) might also increase the risk for CDI. NSAIDs include medications such as ibuprofen, naproxen, indomethacin, and others. Because NSAID use is so common, if it is a risk factor for the acquisition of, or severity of, CDI, that would be important because that would be a modifiable risk factor. We therefore sought to determine the impact of NSAID exposure on CDI severity in a mouse model of antibiotic-associated CDI. We also sought evidence for possible mechanisms whereby NSAIDs might increase the risk for CDI.
Author Interviews, C. difficile, Critical Care - Intensive Care - ICUs, Infections / 07.10.2018

MedicalResearch.com Interview with: Richard Hengel, MD, FRCPC, FACP Atlanta ID Group Richard Hengel, MD, FRCPC, FACP Atlanta ID Group MedicalResearch.com: What is the background for this study? How does Bezlotoxumab differ from other medications for recurrent C. difficile infections? Response: Clostridium difficile infection (CDI) is now the most common hospital acquired infection in the United States, accounting for significant morbidity and mortality, not only in the US, but around the world. Despite standard antibiotic therapy targeting the Clostridium difficile bacterium directly, recurrent infection is common, occurring in a quarter to a third of patients, often frail individuals with other concurrent medical problems. These patients can have multiple recurrences leading to their progressive deterioration over time. Until recently, the only treatment for CDI included antibiotics. More recently, fecal microbiota transplant is a promising, but as yet, FDA unapproved therapy. Bezlotoximab is a new FDA approved treatment for recurrent Clostridium difficile infection (rCDI) that compliments standard antibiotics. Bezlotoxumab is a monoclonal antibody targeting toxin B produced by Clostridium difficile during CDI. In two large treatment trials, bezotoxumab, in addition to standard-of-care antibiotics, reduced the frequency of CDI recurrences from about 28% to about 18%. In this study, we set out to see if this new drug performed as well in actual clinical practice as it did in the published clinical trials.
Author Interviews, Baylor College of Medicine Houston, C. difficile, Nature / 05.01.2018

MedicalResearch.com Interview with: [caption id="attachment_39226" align="alignleft" width="200"]Professor Robert Britton PhD Therapeutic Microbiology Laboratory Department of Molecular Virology and Microbiology Alkek Center for Metagenomics and Microbiome Research Baylor College of Medicine Prof. Britton[/caption] Professor Robert Britton PhD Therapeutic Microbiology Laboratory Department of Molecular Virology and Microbiology Alkek Center for Metagenomics and Microbiome Research Baylor College of Medicine MedicalResearch.com Interview: How would you summarise your findings? Response: As a brief summary of our work, certain strains of Clostridium difficile have emerged in the past 20 years that have resulted in epidemics worldwide, leading to C. difficile becoming one of the most common causes of hospital acquired infections.  Two ribotypes of C. difficile, RT027 and RT078, emerged as key epidemic ribotypes associated with increased disease prevalence and increased mortality in patients.  We found that both of these ribotypes have acquired the ability to consume the disaccharide trehalose by two completely independent mechanisms.  We further show that trehalose enhances disease severity of C. difficile infection in a manner that requires C. difficile to metabolize trehalose in mice.  We also show that trehalose is present in the distal intestine of mice and humans in concentrations that the RT027 ribotype can metabolize.  Because RT027 and RT078 strains were present in clinics at least 10-20 years prior to their becoming epidemic isolates, we looked where people would acquire trehalose in the diet. In 2000 the FDA approved trehalose for human consumption (EFSA did so in 2001) and based on the GRAS report from the FDA the amount of trehalose predicted to be consumed once released on the market would vastly increase what people get naturally from the diet.  Our data support that these two ribotypes increased in prevalence due to a change in the human diet.
Author Interviews, C. difficile, Gastrointestinal Disease, JAMA, Transplantation / 06.12.2017

MedicalResearch.com Interview with: [caption id="attachment_38717" align="alignleft" width="231"]Clostridium difficile CDC image Clostridium difficile
CDC image[/caption] 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.
Author Interviews, C. difficile, Critical Care - Intensive Care - ICUs, Infections, JAMA, Outcomes & Safety / 18.10.2017

MedicalResearch.com Interview with: [caption id="attachment_37568" align="alignleft" width="130"]Dr. Robert Hiensch MD Assistant Professor, Medicine, Pulmonary, Critical Care and Sleep Medicine Icahn School of Medicine at Mount Sinai Dr. Hiensch[/caption] 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.
Author Interviews, C. difficile, CDC, Dental Research, Infections / 09.10.2017

MedicalResearch.com Interview with: [caption id="attachment_37324" align="alignleft" width="200"]Stacy Holzbauer, DVM, MPH, DACVPM CDC Career Epidemiology Field Officer (CEFO) Commander, USPHS Minnesota Department of Health St. Paul, MN Dr. Holzbauer[/caption] 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.
Author Interviews, C. difficile, Infections, Microbiome / 09.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34420" align="alignleft" width="200"]Synthetic Biologics, Inc. Synthetic Biologics, Inc.[/caption] 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. [caption id="attachment_34487" align="alignleft" width="200"]Dr-Sheila-Connelly.jpg Dr. Sheila Connelly[/caption] 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.
Author Interviews, C. difficile, Gastrointestinal Disease, JAMA, Mayo Clinic / 29.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33270" align="alignleft" width="166"]Sahil Khanna, Dr. Sahil Khanna[/caption] 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.
Author Interviews, C. difficile, Gastrointestinal Disease, Microbiome, Transplantation / 14.03.2017

MedicalResearch.com Interview with: [caption id="attachment_32899" align="alignleft" width="100"]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[/caption] 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.
Author Interviews, C. difficile, Hospital Acquired, JAMA / 06.02.2017

MedicalResearch.com Interview with: [caption id="attachment_31754" align="alignleft" width="200"]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[/caption] 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.
Author Interviews, C. difficile / 21.11.2016

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.
Author Interviews, C. difficile, CDC, Infections, Outcomes & Safety / 07.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29447" align="alignleft" width="200"]Dr. Shannon Novosad, MD Epidemic Intelligence Service, CDC Division of Healthcare Quality Promotion National Center for Emerging and Zoonotic Infectious Diseases Dr. Shannon Novosad[/caption] 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.
Author Interviews, C. difficile, Columbia, Hospital Acquired, JAMA / 12.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28610" align="alignleft" width="199"]Dr. Daniel E. Freedberg MD M Dr. Daniel E. Freedberg[/caption] 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.
Author Interviews, C. difficile, Microbiome, Nature, Vanderbilt / 28.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28403" align="alignleft" width="147"]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,[/caption] 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.
Author Interviews, C. difficile, Genetic Research, Infections / 19.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27186" align="alignleft" width="141"]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[/caption] 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.
Author Interviews, C. difficile, Probiotics / 24.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24571" align="alignleft" width="161"]Dr. Nicole Shen New York-Presbyterian/Weill Cornell Medical College Dr. Nicole Shen[/caption] 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.
Author Interviews, C. difficile, Hospital Acquired, JAMA, McGill / 26.04.2016

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.
Author Interviews, C. difficile, Hospital Acquired, Infections, Microbiome / 07.01.2016

[caption id="attachment_20480" align="alignleft" width="128"]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[/caption] 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.
Author Interviews, C. difficile, Gastrointestinal Disease, Transplantation / 22.10.2015

[caption id="attachment_18592" align="alignleft" width="214"]Monika Fischer, MD, MSCR Assistant Professor of Clinical Medicine Division of Gastroenterology and Hepatology Indiana University Indianapolis, IN 46202 Dr. Monika Fischer[/caption] 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.
Author Interviews, C. difficile, Gastrointestinal Disease, Mayo Clinic, Microbiome, Transplantation / 22.10.2015

[caption id="attachment_18565" align="alignleft" width="125"]Dr. Sahil Khanna MBBS Assistant Professor of Medicine Mayo Clinic Dr. Sahil Khanna[/caption] 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..
Author Interviews, C. difficile, JAMA, UC Davis / 08.09.2015

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.
Author Interviews, C. difficile, Infections / 30.07.2015

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.
Author Interviews, C. difficile, Columbia, Gastrointestinal Disease, Microbiome, Pediatrics / 19.06.2015

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.