Author Archives: cdifffoundation

Researchers Find Sulfated glycosaminoglycans and Low-Density Lipoprotein Receptor Contribute To Clostridioides difficile Toxin A Cell Entry

 

Abstract

Clostridium difficile toxin A (TcdA) is a major exotoxin contributing to disruption of the colonic epithelium during C. difficile infection. TcdA contains a carbohydrate-binding combined repetitive oligopeptides (CROPs) domain that mediates its attachment to cell surfaces, but recent data suggest the existence of CROPs-independent receptors. Here, we carried out genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated screens using a truncated TcdA lacking the CROPs, and identified sulfated glycosaminoglycans (sGAGs) and low-density lipoprotein receptor (LDLR) as host factors contributing to binding and entry of TcdA. TcdA recognizes the sulfation group in sGAGs. Blocking sulfation and glycosaminoglycan synthesis reduces TcdA binding and entry into cells. Binding of TcdA to the colonic epithelium can be reduced by surfen, a small molecule that masks sGAGs, by GM-1111, a sulfated heparan sulfate analogue, and by sulfated cyclodextrin, a sulfated small molecule. Cells lacking LDLR also show reduced sensitivity to TcdA, although binding between LDLR and TcdA are not detected, suggesting that LDLR may facilitate endocytosis of TcdA. Finally, GM-1111 reduces TcdA-induced fluid accumulation and tissue damage in the colon in a mouse model in which TcdA is injected into the caecum. These data demonstrate in vivo and pathological relevance of TcdA-sGAGs interactions, and reveal a potential therapeutic approach of protecting colonic tissues by blocking these interactions.

To view abstract in its entirety please click on the following link to be redirected:  https://www.ncbi.nlm.nih.gov/pubmed/31160825?dopt=Abstract&utm_source=dlvr.it&utm_medium=twitter

A Systematic Review Evaluates the Diagnostic Accuracy of Laboratory Testing Algorithms that Include Nucleic Acid Amplification Tests (NAATs) to Detect the Presence of C. difficile

SUMMARY

The evidence base for the optimal laboratory diagnosis of Clostridioides (Clostridium) difficile in adults is currently unresolved due to the uncertain performance characteristics and various combinations of tests.

This systematic review evaluates the diagnostic accuracy of laboratory testing algorithms that include nucleic acid amplification tests (NAATs) to detect the presence of C. difficile. The systematic review and meta-analysis included eligible studies (those that had PICO [population, intervention, comparison, outcome] elements) that assessed the diagnostic accuracy of NAAT alone or following glutamate dehydrogenase (GDH) enzyme immunoassays (EIAs) or GDH EIAs plus C. difficile toxin EIAs (toxin). The diagnostic yield of NAAT for repeat testing after an initial negative result was also assessed.

Two hundred thirty-eight studies met inclusion criteria. Seventy-two of these studies had sufficient data for meta-analysis. The strength of evidence ranged from high to insufficient. The uses of NAAT only, GDH-positive EIA followed by NAAT, and GDH-positive/toxin-negative EIA followed by NAAT are all recommended as American Society for Microbiology (ASM) best practices for the detection of the C. difficile toxin gene or organism. Meta-analysis of published evidence supports the use of testing algorithms that use NAAT alone or in combination with GDH or GDH plus toxin EIA to detect the presence of C. difficile in adults. There is insufficient evidence to recommend against repeat testing of the sample using NAAT after an initial negative result due to a lack of evidence of harm (i.e., financial, length of stay, or delay of treatment) as specified by the Laboratory Medicine Best Practices (LMBP) systematic review method in making such an assessment. Findings from this systematic review provide clarity to diagnostic testing strategies and highlight gaps, such as low numbers of GDH/toxin/PCR studies, in existing evidence on diagnostic performance, which can be used to guide future clinical research studies.

SOURCE:  To Learn More:  https://cmr.asm.org/content/32/3/e00032-18.long?utm_source=dlvr.it&utm_medium=twitter

INTRODUCTION

Clostridioides (Clostridium) difficile infection (CDI) is the leading cause of health care-associated infections in the United States (1, 2). It accounts for 15% to 25% of health care-associated diarrhea cases in all health care settings, with 453,000 documented cases of CDI and 29,000 deaths in the United States in 2015 (3). Acquisition of C. difficile as a health care-associated infection (HAI) is associated with increased morbidity and mortality. This adds a significant burden to the health care system by increasing the length of hospital stay and readmission rates, with significant financial implications. The cost of hospital-associated CDI ranges from $10,000 to $20,000 per case (47) and $500 million to $1.5 billion per year nationally (1, 4, 5, 810).

Accurate diagnosis of CDI is critical for effective patient management and implementation of infection control measures to prevent transmission (11). The diagnosis of CDI requires the combination of appropriate test ordering and accurate laboratory testing to differentiate CDI from non-CDI diarrheal cases, including non-CDI diarrhea in a C. difficile-colonized patient (8). Accurate diagnosis of CDI is critical for appropriate patient management and reduction of harms that may arise from diagnostic error (12) and is critical for implementation of infection control measures to prevent transmission (11). Consequently, among patients presenting with diarrhea, there is significant potential for underdiagnosis or overdiagnosis as can arise from incorrect diagnostic workups (13).

Quality Gap: Factors Associated with the Laboratory Diagnosis of C. difficile

Best practices for laboratory diagnosis of CDI remain controversial (14). Current laboratory practice is not standardized, with wide variation in test methods and diagnostic algorithms. Several laboratory assays are available to support CDI diagnosis in combination with clinical presentation. These include toxigenic culture (TC); the cell cytotoxicity neutralization assay (CCNA); enzyme immunoassays (EIAs) and immunochromatographic assays for the detection of glutamate dehydrogenase (GDH), toxin A or B, or both toxins; and, within the last 10 years, nucleic acid amplification tests (NAATs). Currently, two tests, TC and the CCNA, serve as reference methods for the diagnosis of C. difficile infection (15). The principle of the TC test is to detect strains of C. difficile that produce a toxin(s) following culture on an appropriate medium. CCNA detects fecal protein toxins contained within the stool and is often referred to as fecal toxin detection (16). Unfortunately, both tests are slow and labor-intensive.

Commercially available NAATs for C. difficile detection include those based on PCR or loop-mediated or helicase-dependent isothermal amplification (1720). The performance of NAATs and non-NAAT tests is commonly assessed using diagnostic accuracy measures for the presence of the organism (e.g., diagnostic sensitivity, diagnostic specificity, positive predictive value [PPV], and negative predictive value [NPV]). However, these measures may not directly link to the clinical definition of CDI or clinical outcomes, and some measures (e.g., PPV and NPV) are dependent on disease prevalence in the patient population being tested (8, 17, 19, 20). Finally, in addition to diagnostic sensitivity and specificity, other factors influence the choice of testing strategy, such as cost and turnaround time.

The diagnostic accuracies of current commercially available assays (GDH EIAs, toxin A/B EIAs, and NAATs) are based on comparison with one or both of the currently accepted reference methods (TC and CCNA) for the detection of toxigenic C. difficile, and these comparisons are generally made to inform potential replacement of these reference methods. Although a definitive reference “gold standard” is lacking, both TC and CCNA are regarded as acceptable reference methods (15). However, some view the gold standard to be TC of a stool specimen combined with colonic histopathology of pseudomembranous colitis in patients with symptoms, but it is known that there is a spectrum of disease wherein not all patients with C. difficile infection have pseudomembranes (21). Finally, less frequently, colonoscopic or histopathologic findings demonstrating pseudomembranous colitis can be used in diagnostic workups to increase the diagnostic specificity for CDI diagnosis (14).

In contrasting the two reference methods (TC and CCNA), TC, while infrequently performed in clinical laboratories, is regarded as being more analytically sensitive than CCNA for detecting C. difficile in fecal specimens but may have lower diagnostic specificity (and, therefore, a greater likelihood of false-positive [FP] test results). CCNA has been shown to have high diagnostic sensitivity, ranging from 80 to 100%. In addition, CCNA has high diagnostic specificity and positive predictive values as well as having greater clinical utility based upon clinical outcomes (2226). Furthermore, each reference method differs by the target detected: TC detects the presence of C. difficile strains that produce toxins A and/or B in vitro to confirm a toxigenic strain, whereas CCNA detects the presence of free toxin A or B in clinical specimens. Given these contrasting characteristics, there is potential for diagnostic discrepancy between the reference standards. Therefore, observed diagnostic performance may vary according to which reference standard is used.

Given the variety of test methods and diagnostic algorithms, there is disagreement in the laboratory community on whether best practices for the diagnosis of CDI consist of NAAT only or algorithmic testing that includes NAAT (GDH EIA followed by NAAT [GDH/NAAT] or GDH and toxin EIAs followed by NAAT [GDH/toxin/NAAT]) (20). At the initiation of these guidelines, this was the clinical quandary facing individuals who decide on a C. difficile testing strategy for their health care system, particularly as there is limited high-quality evidence to support which diagnostic testing strategy best supports the laboratory diagnosis of CDI (8, 22). Additionally, it remains to be determined if the potential differences in the accuracy of NAAT only or an algorithmic strategy would impact patient management or patient outcomes (27). There are few studies that encompass the nuances of laboratory CDI diagnosis as it occurs in the clinical context, for example, that evaluate the effect of preanalytic testing considerations on outcomes, to include clinical outcomes. This limitation is evident from the recent Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America (SHEA) systematic review, which included only studies that encompassed C. difficile testing within its clinical context, including preanalytic and postanalytic aspects (11).

Given these practice issues, and related diagnostic quality and patient safety concerns, the goal of this systematic review was to determine which laboratory testing strategies, with the inclusion of NAAT, had the best diagnostic accuracy for CDI. While it is clear that laboratory testing alone without taking into consideration the entire clinical picture is not appropriate for the diagnosis of CDI, the available literature has limited evidence linking laboratory diagnosis with clinical outcomes. Therefore, the questions for this systematic review were refined to be based only on the intermediate outcome of diagnostic accuracy for detecting the presence of the C. difficile organism or toxin. Although the reference standard in these studies defines what is meant by the target condition, this systematic review compares the diagnostic accuracies of these tests, including GDH detection by EIA, toxin detection by EIA, and NAAT, to those of CCNA and TC. It has been clear that preanalytical factors are crucial for NAAT specifically, and many of the studies did not include a preanalytical component, which limits whether this review can answer the question, Does this patient have C. difficile infection?

The questions that guided this systematic review were the following: (i) What is the diagnostic accuracy of NAAT only versus either TC or CCNA for detection of the C. difficile toxin gene?, (ii) What is the diagnostic accuracy of a GDH-positive EIA followed by NAAT versus either TC or CCNA for detection of the C. difficile organism/toxin gene?, (iii) What is the diagnostic accuracy of a GDH-positive/toxin-negative EIA followed by NAAT versus either TC or CCNA for detection of the C. difficile organism/toxin/toxin gene?, and (iv) What is the increased diagnostic yield of repeat testing using NAAT after an initial negative result for C. difficile detection of the toxin gene?

The goals of analysis based on these questions were specifically to evaluate the effectiveness of the following: (i) the diagnostic accuracies of NAAT-only and algorithmic (“two-step” or “three-step”) testing strategies, including detection of toxin or GDH in addition to NAAT, and (ii) the diagnostic yield of repeat testing after an initial negative NAAT result. The evidence supporting these two important issues was evaluated by applying the Centers for Disease Control and Prevention (CDC) Laboratory Medicine Best Practices (LMBP) Initiative’s systematic review method for translating results into evidence-based recommendations (28). The method has recently been used to evaluate practices for improving blood culture contamination (29), blood sample hemolysis (30), urine culture sample quality (31), timeliness of providing targeted therapy for bloodstream infections (32), and laboratory test utilization (33), in addition to others, and can be found at the CDC LMBP website (https://www.cdc.gov/labbestpractices/our-findings.html).

Natural Ways to Keep Ticks Away From You and Your Pets

Tick Season has arrived and is in full-swing.

There are natural ways to keep the ticks away and decrease their existence.  This will help both you and your pets and decrease the risks in having a tick bite and acquiring Lyme Disease

It is recommended to keep the weeds down.  Ticks live in tall grass, weedy areas and in shrubs where they can easily hitch a ride on pets and people as they brush past. You can prevent ticks in your yard simply by keeping it well mowed. In your gardens, keep the weeds down as much as possible and maintain plenty of space between shrubs and perennials. This helps cut down on the number of places for ticks to hide, and it also makes it easier for your pets to walk through the gardens without brushing against the plants.

It’s a good time for the long-haired pets to try a shorter-summer haircut.  Ticks are a bigger problem for cats and dogs with long hair because all that fluff makes it easier for ticks to hitch a ride and hide. Consider giving your dog a short summer clip (but not too short because it protects them from sunburn). If you’d rather not trim a long-haired cat for the summer, your best bet may be to keep the kitty indoors or give them a confined outdoor area away from high grass and weedy spots. Be certain to do a thorough tick check before heading inside.

Try a Lint Roller.  After going for a walk in the woods, use a tape-style lint roller on your slacks, socks, sleeved shirts, jackets, and if there is a fellow-walker or group together — take turns rolling the lint roller across the clothing of each other to remove any hidden ticks and us the lint roller on your dog to pick up any ticks that have decided to hitch a ride

Add Food-Grade DE to the Gardens.   You can maintain plenty of space and weed regularly, and still there may be a few ticks hiding in your flowers and shrubs. You can protect your pets by using food-grade diatomaceous earth (DE) in the gardens. Because it dehydrates insects, this is an effective solution against ticks, fleas, and other pests.   Diatomaceous earth (sometimes to referred to simply as DE) is one of those handy substances that has all kinds of uses around the home and garden. It is mainly used for pest control, effective at killing everything from fleas and roaches indoors to aphids and slugs outdoors.  What is Diatomaceous Earth?   It’s useful, but what is it, exactly?   The short answer is fossils! Diatomaceous earth (pronounced “dia-toMAY-shus” earth) is ground fossilized remains of a type of phytoplankton called diatoms, which have existed on earth for millions of years. Of course, to look at diatomaceous earth, it doesn’t look like fossils and it is more of an off-white powder that looks similar to talc and has no odor.  Contact a local home-improvement garden center for more information.

Frequent Tick Checks.  Despite your best efforts, ticks will find their way onto you and your pets. To prevent tick bites, inspect yourself, your children, and family members along with your pets each day, and preferably each time you have all come in from the outside. With the pets: pay special attention to areas that your pet can’t easily reach such as around the head, behind the ears, and underneath their legs. Smaller deer ticks even hang out on eyelids. It’s a good habit to get into and try to be thorough.  If a tick is located contact a health care provider and for the pets contact their veterinarian to discuss tick removal and treatments.

Preventing Lyme Disease = Preventing Antibiotic Therapy = C.difficile Prevention and MORE.

Working together to prevent pain and suffering in both individuals and our pets. 

National and State Healthcare-associated Infection (HAI) Progress Report from the CDC 2019

Between 2016 and 2017, healthcare-associated infections decreased in the United States, according to the most recent National and State HAI Progress Report   from the CDC.

The report includes a summary of rates for select HAIs across four settings: acute care hospitals, critical access hospitals, inpatient rehabilitation facilities and long-term acute care hospitals.

Key findings from the report include:

1. Central line-associated bloodstream infections saw a 9 percent decrease, with the largest decrease occurring in hospital wards.

2. Catheter-associated urinary tract infections dropped by 5 percent, with ICUs showing the largest decrease of 8 percent.

3. Methicillin-resistant Staphylococcus aureus bacteremia declined by 8 percent and Clostridioides difficile events reduced by 13 percent.

4. Ventilator-associated events and surgical site infections both decreased, by 3 percent and 1 percent respectively. The decrease in SSIs was related to 10 procedures tracked in the report.

5. There were no significant decreases or increases in abdominal hysterectomy SSIs and colon surgery SSIs.

 

Source:  https://www.beckershospitalreview.com/quality/hais-decreased-in-2017-c-diff-down-13-mrsa-down-8.html

C Diff Foundation Welcomes Dr. Sahil Khanna, M.B.B.S.

We are pleased to welcome Dr. Sahil Khanna
as a Member of the C Diff Foundation and Medical Advisory Board.

Dr. Sahil Khanna is an Associate Professor of Medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic, Rochester, MN. He is directing the Comprehensive Gastroenterology Interest group,
C. difficile Clinic, Fecal Microbiota Transplantation program and
C. difficile related Clinical Trials at Mayo Clinic, Rochester, MN.

He completed Medical School at the All India Institute of Medical Sciences, New Delhi; followed by Post Doctoral Research at University of California San Diego, CA; residency in Internal Medicine and Fellowship in Gastroenterology and Hepatology at Mayo Clinic, Rochester, MN before joining the Faculty. He also completed Masters in Clinical and Translational Sciences during his fellowship. His research and clinical interests include Epidemiology, Outcomes and Emerging Therapeutics for Clostridium difficile infection, an arena in which he has had numerous publications and presentations.

Dr. Khanna has over 100 peer-reviewed publications and serves as reviewer and on the editorial board of several journals. He has won numerous awards including the Miles and Shirley Fiterman Award, Mayo Brothers Distinguished Fellowship Award, Donald C. Balfour Mayo Clinic Alumni Association Research Award, Hartz Foundation Young Investigators’ Scholarship and the Most Distinguished Resident Physician Award from the American Association of Physicians of Indian Origin.

Food Safety Tips to Reduce Risk of a Food-borne Illness During a Holiday Gathering – Memorial Day Message

Remembering those who sacrificed everything so we could have anything

It takes courage to keep the faith of the people alive and fight with courage for the people of the country. Our soldiers deserve all the honor and respect.

A bit of history:  Memorial Day, originally called Decoration Day, is a day of remembrance for those who have died in service of the United States of America. Over two dozen cities and towns claim to be the birthplace of Memorial Day. While Waterloo N.Y. was officially declared the birthplace of Memorial Day by President Lyndon Johnson in May 1966, it’s difficult to prove conclusively the origins of the day.

Each and every soldier who fought for the nation was someone’s son or daughter, someone’s brother or sister, someone’s  Mother or Father, and someone’s friend….. Memorial Day is the day to take inspiration from such brave soldiers and stand with their families.   On this  occasion, let us bow our heads in silence to remember and honor the sacrifices of hundreds of men and women who gave their lives for the country.

Sending warm wishes to you and your family on Memorial Day.

 

 

 

During the Memorial Holiday and during the many festivities taking place from towns to cities — it is a good time to take a “hand-washing break”

Wash your hands with soap and clean running water for about 20 seconds and if soap and clean water are not available, use an alcohol-based product.  Alcohol-based hand rubs significantly reduce the number of germs on skin and are fast-acting.

Wash your hands with soap and water during these key times when you are likely to get and spread germs:
  • Before, during, and after preparing food
  • After touching raw meat, raw eggs, or unwashed vegetables
  • Before eating or drinking
  • Before and after caring for someone who is sick
  • Before and after treating a cut or wound
  • After blowing your nose, coughing, or sneezing
  • Before exiting a restroom *
  • After changing diapers or cleaning up a child who has used the toilet
  • After touching an animal, animal feed, or animal waste
  • After touching garbage.

FOOD SAFETY TIPS ~ Backyard Gatherings to Picnics

Serve Foods Safely

  • If preparing food in advance, divide cooked food into shallow containers  and store in a refrigerator or freezer. This encourages rapid, even cooling.
  • Keep hot foods hot, at 140°F or warmer. Use slow cookers, chafing dishes, and warming trays to keep food hot on the buffet table.
  • Keep cold foods col , at 40°F or lower. Use small serving trays and replace often with fresh platters from the refrigerator, or place serving dishes in bowls of ice so they stay chilled.
  • For picnics and other outdoor meals, keep cold food in a cooler filled with ice or frozen gel packs until just before serving. Catering or getting food delivered?     Make sure food that is catered or delivered stays at a safe temperature.
store leftovers in smaller portions

Divide leftovers into smaller portions or pieces, place in shallow containers, and refrigerate or freeze.

The Two-Hour Rule:  Throw away any perishable foods that have been out at room temperature for 2 hours or more.

Toss them after 1 hour if they’ve been sitting out at temperatures of 90°F or hotter, such as food served at a picnic or outdoor family reunion.

Taking temperature of foods

Use a food thermometer to be sure foods are cooked to the right temperature.

  • Store and Reheat Leftovers the Correct Way >>>>
  • Divide leftovers into smaller portions or pieces, place in shallow containers, and refrigerate or freeze.
  • Leftover foods should be refrigerated at 40°F or below as soon as possible and within two hours of preparation. It’s OK to put hot foods directly into the refrigerator.
  • Leftovers should be reheated to at least 165°F before serving. This includes leftovers warmed up in the microwave.

Have  a Safe Holiday!

Source:  https://www.cdc.gov/foodsafety/serving-food-safely.html

C Diff Foundation Announces Appointment of Paul Feuerstadt, M.D., Director of Medical Education

C Diff Foundation, a one hundred percent volunteer, world renowned 501(c)(3) not-for-profit organization, has appointed nationally renowned Gastroenterologist, Dr. Paul Feuerstadt as its first Director of Medical Education.

Dr. Feuerstadt said, “It is my honor to accept this position. I have been involved with the C Diff Foundation over the last 4.5 years and I look forward to assisting in the continued growth of the organization and ensuring that forward progress, awareness and education increases under my tenure. I look forward to working with the board and volunteers to increase awareness and funding across the country and around the world to highlight this disease through in person events, social media, and in the press.”

Dr. Feuerstadt has spent his career refining his practice and expertise in C. difficile. He is dedicated to educating the public through his work with this organization.

Additionally, he plans to offer free patient and provider education through the launch of his new educational website, EverythingCdifficile.com. The goal of the site is to provide education through short videos with relevant clinical information for educational purposes. The site provides concise 3-5 minute lectures covering core topics, recent publications and major conferences about C. difficile infection to educate both patients and providers.

Nancy C. Caralla, Founding President, C Diff Foundation, commented: “Dr. Feuerstadt is a pre-eminent doctor in this space. His dedication and donation of his time and energy to this worthy cause has helped so many patients to date. We look forward to his enhanced leadership and knowledge as the organization grows and strengthens through our advocacy in
the C.diff. community. Dr. Feuerstadt’s new role as Director of Medical Education will provide an additional avenue of support to patients, families, caregivers, and healthcare providers  through his educational media available on EverythingCdifficile.com. We are grateful for Dr. Feuerstadt’s time and dedication as we continue fighting this debilitating disease worldwide.”

About Dr. Paul Feuerstadt:

His areas of interest Clostridioides difficile infection and ischemic diseases of the gut and in these areas he has presented his research extensively, authored and co-authored many manuscripts, textbook chapters and online modules. Another passion of Dr. Feuerstadt’s is teaching, frequently giving lectures locally, regionally and nationally. He holds a clinical appointment as an Assistant Clinical Professor of Medicine at the Yale University School of Medicine and is a full time attending physician at the Gastroenterology Center of Connecticut seeing patients with a broad spectrum of clinical gastroenterological diseases.

Dr. Feuerstadt attended the Weill Medical College of Cornell University in Manhattan for medical school and completed his residency in internal medicine at New York Presbyterian Hospital/Weill Cornell. His clinical fellowship training was completed at Montefiore Medical Center in the Bronx, New York.