Author Archives: cdifffoundation

Merck and Premier Applied Sciences Will Develop Software To Provide C.difficile Infection Education and Provide Surveillance

Merck & Co is working a major US hospital provider on a new software system that could help tackle the threat from healthcare-associated infections, the leading HAI:   C. diff.  infections.

 

 

 

The pharma company’s deal with Premier will see the partners develop and test the combination of a software-based platform and a coordinator to provide surveillance, consultation, support and education to patients with Clostridium difficile infection (C. diff).

Sam Bozzette, MD, chief scientist of Premier’s retrospective and interventional research division Premier Applied Sciences, said: “By increasing clinician and patient knowledge of this often prolonged, and sometimes deadly infection, and developing and testing a software-based application to help reduce the recurrence of C. diff. infection by improving follow-up and management, we believe there is a strong potential to make a real difference to address this critical public health problem.”

Sam Bozzette, MD, PhD, vice president and chief scientist of its retrospective and interventional research division, Premier Applied Sciences.  An internationally-recognized researcher and physician executive, Dr. Bozzette provides strategic clinical, analytical and operational direction to further grow the Premier Applied Sciences research business and improve the overall quality, safety and cost-effectiveness of care.  “Dr. Bozzette is a leader in medical and social sciences, and has more than 25 years of experience working with academic and non-profit healthcare providers to improve clinical decision-making practices, care delivery efficiency and effectiveness, and population health management,” said Leigh Anderson, chief information officer at Premier. “We are thrilled to have him on board to lead Premier’s data-driven research efforts to set new standards in care delivery through strategic partnerships with healthcare industry leaders across the U.S.”

Premier Applied Sciences, formerly known as Premier Research Services, combines data and analytics with objective clinical outcomes analyses, and partnerships with health systems, life sciences companies, academic institutions and professional societies to develop, teach, test and research care delivery practices and real-world interventions for healthcare improvement. It offers real-world research and analytics, retrospective research, healthcare education, clinical trial innovation and data licensing services.

Resources:  https://pharmaphorum.com/news/merck-co-software-c-diff-infections/

https://www.premierinc.com/dr-sam-bozzette-joins-premier-inc-lead-research-division/

The work expands Merck’s chronic disease work with Premier, which has seen them co-develop and test solutions that help promote wellness and prevention for specific groups of at-risk patients since 2016.

Raquel Tapia, associate VP, hospital/specialty marketing at Merck, said: “Combining the technical capabilities of Premier and the therapeutic area expertise of Merck has been instrumental in our ability to address these difficult healthcare challenges.

“By testing the solutions in real-world settings and learning from our growing knowledge base, we’re confident that our work together will help patients.”

The partners’ goal is to increase patient access to healthcare services, raise awareness of how to decrease patient risk of recurrence and help patients identify if they are having a recurrence.

The proposed C. diff software intervention will be tested within volunteer Premier member health systems. The firm current has an alliance of around 3,900 US hospitals and health systems and a further 150,000 or so healthcare providers and organizations.

C. diff infections cause serious and life-threatening diarrhea and have become one of the most common microbial cause of healthcare-associated infections in US hospitals. It’s thought that C. diff infections affect approximately half a million people and add $4.8 billion to US healthcare costs each year.

There Are Smart Antibiotics to treat C.difficile infections being developed by Researchers

Cationic amphiphilic bolaamphiphile-based delivery of antisense oligonucleotides provides a potentially microbiome sparing treatment

for C. difficile

The Journal of Antibiotics (2018) | Download Citation

Abstract

Conventional antibiotics for C. difficile infection (CDI) have mechanisms of action without organismal specificity, potentially perpetuating the dysbiosis contributing to CDI, making antisense approaches an attractive alternative. Here, three (APDE-8, CODE-9, and CYDE-21) novel cationic amphiphilic bolaamphiphiles (CABs) were synthesized and tested for their ability to form nano-sized vesicles or vesicle-like aggregates (CABVs), which were characterized based on their physiochemical properties, their antibacterial activities, and their toxicity toward colonocyte (Caco-2) cell cultures. The antibacterial activity of empty CABVs was tested against cultures of E. coli, B. fragilis, and E. faecalis, and against C. difficile by “loading” CABVs with 25-mer antisense oligonucleotides (ASO) targeting dnaE. Our results demonstrate that empty CABVs have minimal colonocyte toxicity until concentrations of 71 µM, with CODE-9 demonstrating the least toxicity. Empty CABVs had little effect on C. difficile growth in culture (MIC90 ≥ 160 µM). While APDE-8 and CODE-9 nanocomplexes demonstrated high MIC90 against C. difficile cultures (>300 µM), CYDE-21 nanocomplexes demonstrated MIC90 at CABV concentrations of 19 µM. Empty CABVs formed from APDE-8 and CODE-9 had virtually no effect on E. coli, B. fragilis, and E. faecalis across all tested concentrations, while empty CYDE-21 demonstrated MIC90 of >160 µM against E. coli and >40 µM against B. fragilisand E. faecalis. Empty CABVs have limited antibacterial activity and they can deliver an amount of ASO effective against C. difficile at CABV concentrations associated with limited colonocyte toxicity, while sparing other bacteria. With further refinement, antisense therapies for CDI may become a viable alternative to conventional antibiotic treatment.

Introduction

C. difficile infection (CDI) is the most frequently reported nosocomial bacterial infection [1] in the United States, accounting for more than 450,000 new cases annually and for more than four billion dollars in CDI-attributable annual health care costs [2]. CDI has a strong reliance on intestinal dysbiotic states, which, when combined with the presence of C. difficile in the human gut, represents the most common pathogenesis for CDI. The high prevalence of this infection is, in large part, due to formidable recurrence rates of 15–25% following first treatment [3] with conventional antibiotics (CAs). CAs have long been recognized as the most important risk factor for the development of CDI [4], due to their mechanisms of action lacking organismal specificity, leading to widespread changes in gut ecology [5], which can lead to CDI by disrupting the gut microbial community. Given the important role of intestinal dysbiosis in the development of CDI, there has also been recent interest in studying the effects of difficile-directed conventional antibiotics on the bacterial and fungal communities of human subjects being treated for CDI, as a way of potentially explaining the high persistence and recurrence rates of this disease. These more recent data [6] suggest that even difficile-directed conventional antibiotics could potentially contribute to the perpetuation of dysbiotic states, which in turn could perpetuate CDI, potentially leading to even primary treatment failures.

There has been previous [7, 8] interest in the development of antisense therapies to treat bacterial infections, in part due to concerns regarding antibiotic resistance to traditional drugs. Given the dependence of CDI on dysbiotic states, approaches using therapeutic antisense oligonucleotides (ASO) complimentary to specific C. difficile mRNAs could limit or prevent the expression of important bacterial genes leading to bacterial death, all while sparing other organisms. This approach would offer significant advantages over CAs, especially in terms of a more limited impact on gut microbial communities. Developing clinically effective antisense therapies targeting a Gram-positive organism requires several elements. Since antisense oligonucleotides will not be efficiently introduced into bacteria without assistance given the presence of both a cell membrane and a thick cell wall, a carrier molecule must be used to deliver the ASO. This carrier must complex with the ASO strongly enough to concentrate it, to protect it from degradation in the extracellular environment, and to focus its delivery on its target cell. In order to accomplish these activities, the carrier-ASO complex itself must be stable in the in vivo environment of the gut. Once at the cell, the carrier must be able to release its cargo. Simultaneously, the carrier must demonstrate both limited gut toxicity and limited antibacterial activity at the doses required to effectively treat the target bacteria.

Our group published the first [9] in vitro data for antisense therapies against CDI by complexing cyclohexyl dequalinium analogs to various ASO-targeting essential C. difficile genes. However, since dequalinium has both antibacterial activity as well as toxicity at higher doses, a better delivery compound for ASO is required if antisense approaches to CDI are to be further developed. Here, we report our data on vesicles formed from novel cationic amphiphilic bolaamphiphiles (CABs) as carriers for chimeric 25-mer 2′-O-methyl phosphorothioate ASO. CABs, characteristic of all bola-like compounds, have hydrophilic, positively charged end groups separated by a hydrophobic linker chain. This molecular structure enables CABs to form nano-sized vesicle-like aggregates (CABVs), which in turn allow them to complex with negatively charged oligonucleotides in addition to promoting electrostatic interactions with bacterial cell membranes for intracellular delivery of ASO. The synthesis, physiochemical properties, toxicity, and antibacterial properties of three novel CABs and their respective CABVs are described, and their specificity for C. difficile compared to several other organisms is also provided.

Please click on the following link to view graphs and read this article in its entirety:

https://www.nature.com/articles/s41429-018-0056-9

The C Diff Foundation Welcomes Weiyan Feng, Pharm.D., RPh To the Antimicrobial Stewardship and CDI Prevention (ASCP) Committee

It is a pleasure to welcome
Weiyan Feng Pharm.D., RPh to the C Diff Foundation’s Antimicrobial Stewardship and CDI Prevention (ASCP) Committee

 

Weiyan Feng is the Associate Director, Medical Affairs at CutisPharma. Currently, she leads the Medical Affairs department in strategic medical planning and project management of medical initiatives. She is responsible for assuring that there is medical and pharmaceutical science support throughout product cycle (Pre-launch (development), Launch and Post-launch). She has led advisory boards, represented CutisPharma at key medical congress/conferences, and presented to diverse audiences. Prior to joining CutisPharma, Dr. Feng’s has practiced in institutional and retail pharmacy settings. Her background in pharmacy includes pharmaceutical compounding, clinical pharmacology, patient safety, and process development and improvement. She has a passion for advocating the prevention, treatment, and awareness building of medical conditions, especially Clostridium difficile Infection.

Watermelon; A Fruit Filled With Healthy Benefits

The healthy or beneficial effects of watermelon are mainly derived from its unique nutrients, vitamins, minerals, and organic compounds.

These include significant amounts of vitamin C, calcium, magnesium, fiber, protein, and a large amount of potassium. Furthermore, they contain vitamin A, vitamin B6, niacin, thiamin, and a wide variety of carotenoids and phytonutrients, including lycopene.

Did you know that Watermelon is effective in reducing both your body temperature and blood pressure?

Many people in tropical regions eat Watermelon on a daily basis during the summer to protect themselves from heat stroke. The high amount of water found in watermelons also helps in preventing dehydration.  At only 46 calories per cup, it is a beneficial fruit to add into the daily diet, especially during the hot summer weather, before/after a workout and when a patient is being treated for a G.I. diagnosis, such
as a C. difficile infection, that can cause a fluid shift and loss of body fluids.

According to a new study in the Journal of Agricultural Food and Chemistry, drinking watermelon juice before a hard workout helped reduce athletes’ heart rate and next-day muscle soreness. That’s because watermelon is rich in an amino acid called L-citrulline, which the body converts to L-arginine, an essential amino acid that helps relax blood vessels and improve circulation.

The study’s seven participants, all men, were given 17 ounces (500 mL) of either natural watermelon juice, watermelon juice enriched with additional citrulline, or a placebo drink an hour before their workouts. Interestingly, the natural juice was just as effective as the enriched juice. The researchers also determined that intestinal cells can absorb more citrulline from watermelon juice than from citrulline supplements, especially when the juice is unpasteurized.

In just one cup, watermelon has 1.5 times the stuff than a large fresh tomato, 6 milligrams compared to 4 milligrams, according to the USDA. That matters because lycopene is thought to act as a super antioxidant, stopping free radicals from damaging your cells and messing with your immune system.

 

Watermelon can prevent dehydration. Watermelon is 91.5% water, according to the USDA. That’s a big deal seeing as how being dehydrated is bad for your health. A study published in The Journal of Nutrition found that individuals with even mild dehydration experienced headaches, poor concentration, fatigue, and worse moods.

Here are a few cooling and refreshing melon recipes:

Cantaloupe Sherbet
For less than 100 calories, you can enjoy a refreshing dessert. Cantaloupe adds a natural sweetness to the sherbet plus a luscious peach color.

 

 

Ingredients:

  • 1 large ripe cantaloupe, peeled and finely chopped (about 5 cups)
  • 1/3 cup “measures-like-sugar” calorie-free sweetener
  • 2 tablespoons lemon juice
  • 2 teaspoons unflavored gelatin
  • 1/4 cup cold water
  • 1 (8-ounce) carton vanilla fat-free yogurt sweetened with aspartame
  • Cantaloupe wedge (optional)

HOW to prepare:

  • Combine cantaloupe, and lemon juice in a blender of choice or food processor; process until smooth. Transfer mixture to a medium bowl.
  • Sprinkle gelatin over cold water in a small saucepan; let stand 1 minute. Cook over low heat, stirring until gelatin dissolves, about 4 minutes. Add to cantaloupe mixture, stirring well. Add yogurt, stirring until smooth.
  • Pour mixture into an 8-inch square pan; freeze until almost firm.
  • Transfer mixture to a large bowl; beat with a mixer at high speed until fluffy. Spoon mixture back into pan; freeze until firm.

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Watermelon Smoothie

Just 25 calories a 8 ounce serving.

 

 

Ingredients:

  • cup watermelon (cut into cubes)
  • cucumber (peeled and sliced)
  • mint leaves
  • 1/2 cup ice

HOW to prepare:

Place cubed watermelon, one cucumber thinly sliced, two min leaves and 1/2 cup of ice

into blender of choice with 1/4 cup of water.  Blend until smooth.

Pour into glasses and serve.

Freeze remainder of beverage for a refreshing frozen treat.

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Watermelon and Ginger-Ale Smoothie

Just 100 calories per 8 ounce serving.

 

 

Ingredients:

 

  • 3 1/2 cups watermelon (cut into cubes and de-seeded)
  • lime
  • 1 1/2 cups ginger ale
  • cups ice

 

HOW to prepare:

Place cubed watermelon, ginger-ale and ice into blender of choice or a food processor.

Blend well and serve.  Garnish with a slice of lemon or lime.

Freeze the remainder beverage for a tasty treat in a freezer safe container.

 

References:

https://news.nationalgeographic.com/news/2013/08/130820-watermelon-nutrition-health-food-science/

C.difficile (C.diff.) Infections Continue to Grow in Health Care Facilities Worldwide

The burden of Clostridium difficile (C. diff) continues to grow in health care facilities throughout the United States and around the world.

Gaining a better understanding of sources and risk factors for C. diff can help reverse colonization and transmission or prevent it altogether, authors of a new paper suggest.

To view the article in its entirety, please click on the following link to be redirected:

http://www.contagionlive.com/news/exploring-microbiome-changes-associated-with-c-diff-to-prevent-or-reverse-colonization

“This is a review/commentary article that provides a high-level overview of the literature dealing with C. diff colonization and the microbiome changes associated with C. diff colonization,” author Silvia Munoz-Price, MD, PhD, from the Medical College of Wisconsin in Milwaukee told our sister publication MD Magazine.

After reviewing the literature, authors of the study postulated that when it comes to the potential for C. diff colonization, exposure to and transmissions of the virus occurs outside of hospitals. In fact, it seemed like most of the patients became symptomatic during their hospital stay, rather than acquiring the virus while hospitalized.

For example, the investigators cited one study from Canada that had been conducted from 2006 to 2007 where more than 4000 patients were screened for C. diff colonization upon hospitalization, during their stay (on a weekly basis) and at discharge. They found that 4% of the patients were colonized upon hospitalization and 3% acquired C. diff during their stay in the hospital.

The authors also found evidence indicating that community-acquired C. diff appears to be on the rise. The authors discuss a decade-long study which took place in Minnesota where community-acquired C. diff infection rates rose from 2.8 to 14.9 per 100,000-person-years within the 10-year span. The patients in that study more likely to acquire C. diff were younger, female, and healthier than patients with hospitalization acquired C. diff. The reviewers also said that rates of community-acquired C. diff have also been rising in Finland, Australia, and England, according to published studies.

Most of the common risk factors for community-acquired C. diff infections still applied, the researchers found, including antibiotic exposure, household contact, and animals. A 2013 study showed that two-thirds of community-acquired C. difficile patients were exposed to antibiotics in the preceding 12 weeks of their infection, and about one-third had been exposed to proton pump inhibitors.

While studies examining transmissibility within households are difficult to come by, the study authors found one review from Quebec. The review consisted of 2222 cases of C. diff diagnosed between 1998 and 2009, and investigators found that 8 cases were designated to be transmitted by household contacts. However, the researchers noted, confirmation using strain typing was not performed in that study.

Looking at farm livestock, a 2013 Dutch study showed that individuals with daily contact with pigs showed rates of C. diff positivity of 25%; in those with weekly contact, it was 14%. In the same study, C. diff was found in the manure from all the farms in 10% to 80% of the samples per farm. The reviewers also said that C. diff has been found in the stool of farm chickens, calves, and retail ground meat. Dogs and cats are also known to culture positive for C. diff, and the researchers wrote that the bacteria can also be present in vegetables and water (tap water, swimming pools, as well as rivers, lakes, and seas). They hypothesized that the presence of C. diff in vegetables may come from the use of organic fertilizer.

“We envision that in the future we should be able to take advantage of our increasing knowledge about microbiome changes so that we will be able to: identify patients at risk for de novo C. difficile colonization during their hospitalization and manipulate our patients’ microbiome to prevent or reverse C. difficile colonization,” Dr. Munoz-Price said.

“Different from what we do now, the latter would be accomplished not by withholding or changing antibiotics but by correcting the deficient flora of a patient in an individualized fashion. This new approach would revolutionize the field of Infection Control and Antibiotic Stewardship,” she concluded.

The C Diff Foundation Welcomes Allyssa Anderson, PharmD

The C Diff Foundation Welcomes Alyssa Anderson, PharmD to the Foundation’s Antimicrobial Stewardship and CDI Prevention (ASCP) Committee

 

Allyssa Anderson, PharmD attended Purdue University in West Lafayette, IN, where she completed their Pre-Pharmacy program and Doctor of Pharmacy program in a total of 6 years.

As a recent graduate, Allyssa will be completing a PGY-1 residency at Presence Saint Joseph’s Medical Center, which is part of the Presence/Amita Healthcare system. Allyssa aspires to pursue a career in infectious disease pharmacy after her residency program either as a provider or furthering her education with a second year of residency. Throughout her clinical experiences, Allyssa has taken part in several scientific research projects in the area of infectious diseases including, but not limited to, acute osteomyelitis, chronic osteomyelitis, clostridium difficile prophylaxis and prevention, and resistance trends.

In addition, Allyssa is a member of the American Society of Health System Pharmacists (ASHP), along with the American Pharmacists Association.

Antimicrobial Stewardship and CDI Prevention (ASCP) Committee
Chair; Nick VanHise, PharmD, BCPS
Weiyan Feng, PharmD, RP
Allyssa M. Anderson, PharmD
Keith Nguyen, PharmD, BCPS, BCCCP

David Kirk and Ben Bradley Explain the Gut Microbiome and Clostridium difficile

It has access to the largest surface area of the body, alters drugs before they even enter the blood stream and could be a potent medicinal weapon… yet there is much we still don’t understand about the microbiome.

Here David Kirk and Ben Bradley tell us about their attempts to heal us from within

We are not alone. We are inhabited by hundreds of species of microbes, which represent millions of genes. Together, these microscopic organisms – bacteria, fungi, archaea and viruses ­– and their collective genomes make up the microbiome.

To review this article in its entirety please click on the following link:

https://www.labnews.co.uk/interviews/guestbook/therapeutics-live-21-05-2018/

In the gut, microbes break down otherwise indigestible dietary fibres and release nutrients, such as B-vitamins and short chain fatty acids, which can be absorbed by the intestines. They secrete other small molecules or peptides which interact with the body via the bloodstream and immune system. The majority of these have yet to be identified and characterised. In addition, commensal microbes deter opportunistic pathogens from invading the competitive niche of the intestinal tract.

LBPs are a recent concept and have their origins in a novel treatment for C. difficile infection: the faecal microbiota transplant… this is exactly what you think it is

The disruption of the microbiome, termed dysbiosis, is associated with an ever-growing list of conditions. Obesity and metabolic syndrome, for instance, are associated with a microbiome less diverse than that of a healthy individual. Inflammatory bowel disease (IBD) and colorectal cancer are associated with a decrease in butyrate-producing bacteria like Clostridia, and an increase in Enterobacteriaceae and Bacilli.

An air of scepticism comes with the phrase “associated”. Microbiome research is still a developing field, and the presence or absence of a single species or genus cannot be directly blamed for conditions like obesity or IBD in all patients. The complex interplay between host and microbiome depends as much on the host’s genetic susceptibility and environment as on the dysbiosis or lack of diversity in the microbiome. The million dollar question remains: What exactly constitutes a ‘healthy microbiome’?

A powerful tool
The microbiome is adaptive and changes in response to diet, environment and disease. It has become increasingly clear that many drugs interact with the microbiome, with some requiring microbiota derived enzymes for activation and others being rendered non-functional or even toxic via microbiota dependant conversion. As research in host-microbe interaction continues, more accurate relationships between the microbiome and human illness will be uncovered.

The gut microbiome presents an interesting medicinal target in itself. It interacts directly with one of the largest surface areas of the body. Therefore it has easy access to the bloodstream through diffusion of nutrients and small molecules, and via a mucosal layer rich in multiple cell types of the adaptive and innate immune systems. Due to the powerful delivering capacity of the gut, most microbial-based treatments in development aim to add to the microbiome rather than take away from it.

Microbial therapies using living organisms are known as live biotherapeutic products (LBPs). LBPs are a recent concept and have their origins in a novel treatment for C. difficile infection (CDI): the faecal microbiota transplant.

This is exactly what you think it is.

CDI occurs when the gut microbiome is wiped out by antibiotic use and becomes infected by C. difficile, an organism that is normally unable to compete against the natural microbiota. This illness may recur in spite of further antibiotic treatments, and can be fatal. The most effective treatment, in extreme cases, is a faecal transplant into the infected recipient. Transplanted microbes thrive and outcompete C. difficile, effectively reversing the infection in over 90% of cases. But due to the uncertainty of what constitutes a ‘healthy microbiome’, a faecal transplant cannot be considered a cure-all for dysbiosis-associated illness.

Daunting clinical trials
This “unknown” of host-microbe interaction sparked the need to develop defined microbiome therapies. Naturally, CDI was one of the first targets for a defined treatment. Several companies are developing and trialling defined cocktails of bacteria known to safely inhabit the gut with the goal of outcompeting C. difficile with Seres Therapeutics and Rebiotix entering phase 3 trials in 2018.

CHAIN Biotech is developing technology to deliver therapeutics to the gut microbiome using engineered Clostridium, a spore forming bacterium, and have a lead candidate targeting IBD. IBD is a collection of inflammatory diseases of the gut, commonly treated with steroid injections which cause numerous unpleasant side effects. Our approach is to deliver an LBP directly to the gut, where it can produce an anti-inflammatory in situ. We also make use of this species’ natural ability to produce spores, which survive the acidic environment of the stomach and germinates into therapeutic-producing cells only in the anaerobic environment of the lower intestine.

This elementary approach – adding one organism with a safe history of use in the human gut, and having it produce one novel product – minimizes the risk of disruption to the microbiome and delivers the treatment directly to the affected area. The next stages, taking LBPs to clinical trial, are daunting. A lot of unknowns exist around the human gut microbiome and these kinds of treatments. Few microbiome companies have LBPs in late-stage clinical trial, but those that do give hope to both patients and us that LBPs will someday heal us from within.