Author Archives: cdifffoundation

Breakout Labs Has Invested in SciBac, a Company Targeting the Growing Problem of Antibiotic Resistance

It’s not surprising that Breakout Labs, the Thiel Foundation‘s seed-stage fund that aims to propel radical science to improve human health, has invested in SciBac, a company targeting the growing problem of antibiotic resistance. Among health risks that threaten mankind, the one that may prove most deadly is the rise of superbugs — drug-resistant bacteria that can make simple surgeries and medical treatments like chemotherapy impossible.

Why Peter Thiel is backing a tiny start-up waging war against the global superbug crisis

  • 700,000 people worldwide die each year from antibiotic-resistant infections, and numbers are increasing.
  • Antimicrobial resistance is projected to kill more people than cancer by 2050, according to the World Health Organization.
  • Many big pharmaceutical companies are exiting the antibiotic drug development field due to low margins.
  • Start-ups like SciBac, which made the 2018 CNBC Upstart 100 list, are developing alternative solutions.

Over the years ever more powerful strains have spread around the world. It’s a crisis that has even garnered the attention of world leaders at the United Nations. That’s because the urgency is clear: 700,000 people die each year worldwide from antibiotic-resistant infections, and that number is increasing by the day. In the United States alone at least 2 million people become infected with antibiotic-resistant bacteria each year, according to the Centers for Disease Control and Prevention, and 23,000 die each year as a result of those infections.

The future trend is alarming. According to the World Health Organization, Hemai Parthasarathyis projected to kill more people than cancer by 2050, which would reduce global economic output by between 2 percent and 3.5 percent — a staggering $100 trillion cut in GDP globally — and severely cripple modern medical and surgical advances.

A $40 billion superbug market Big Pharma is neglecting

It’s no wonder many scientists call antimicrobial resistance “a slow-motion tsunami.” Yet lack of drug development and discovery by Big Pharma has exacerbated the problem. “Within the last two years, five large pharmaceutical and many biotech companies have exited the field due to the scientific, regulatory and economic challenges posed by antibiotic discovery and development,” said Thomas Cueni, chairman of the AMR Industry Alliance, a coalition of 100 companies and pharmaceutical associations set up to curb antimicrobial resistance. Among the pharmaceutical giants to exit this research field: Novartis, AstraZeneca, Sanofi and Allergan.

The void has spurred many nimble biotech start-ups to look for solutions in this new $40 billion superbug market. One is SciBac, a biotherapeutics company named to the 2018 CNBC Upstart 100 list. The Silicon Valley start-up shifts the paradigm on how to tackle superbugs. It is developing a microbe pill to boost the body’s microbiome in the gut, lungs and skin to kill bacteria that cause antibiotic-resistant disease. Its first product treats and prevents Clostridium difficile infection (CDI), commonly known as deadly diarrhea and our nation’s top antibiotic-resistant threat. It is also working on developing a drug to treat and prevent chronic Pseudomonas infections in the lungs of cystic fibrosis patients.

“Our patented platform technology has applications to treat other infections,” said SciBac CEO Jeanette Mucha. “It allows us to mate different species of microbes into a single hybrid that can target specific diseases through multiple modes of action that kill the bacteria and toxins in the body. At the same time, the technology bolsters the microbiome for fast recovery.”

SciBac CEO, Jeanette Mucha is on a quest to develop an antibiotic alternative.

According to Hemai Parthasarathy, Ph.D., scientific director of the Thiel Foundation’s Breakout Labs, “It’s clear we are running out of an arsenal to attack the superbug crisis, and the world needs new approaches.”

To help SciBac’s team move their technology out of the lab, Breakout has taken a board role to help with business strategy and will help introduce the founders to venture capitalists and potential business partners in the months ahead.

To date, the three-year-old upstart has raised $1.45 million in equity financing and a $3.7 million grant from CARB-X, a nonprofit public-private partnership funded by the U.S. government, Wellcome Trust, the NIH, Bill and Melinda Gates Foundation and the U.K government, that invests in antibacterial research worldwide. Its goal: to fast-track the development of a pipeline of new antibiotics, vaccines and other products to fight the war on superbugs.

“SciBac is essentially creating a new drug that is an antibiotic alternative,” said Kevin Outterson, executive director of CARB-X. “The microbiome is providing exciting new approaches to the prevention and treatment of life-threatening infections of all kinds. It’s a promising new scientific approach.”

SciBac’s answer to the superbug threat has caught the attention of investors.

As Outterson explains, most of the innovation in this field is coming from tiny pre-clinical trial companies like SciBac. That’s because many Big Pharma companies feel the margins aren’t worth the high R&D costs, which can run into the billions of dollars. “As soon as you make an antibiotic, it is already dying because bacteria are evolving in response to the drug. Eventually, random mutations will make antibiotic resistance come.”

For this reason, drug companies feel antibiotics are undervalued in the marketplace.

To help boost the start-up’s odds of success, CARB-X will provide SciBac with consultants and experts in R&D, toxicity and regulation that can help them navigate how to get their science from the lab to clinical trials for FDA approval. It has set milestones for the company that it must meet to get financing.

Like many entrepreneurs pursuing breakthrough science, Mucha seems energized by her formidable challenge of kickstarting the development of a new drug.

Mucha said she and co-founders Anthony Cann, a chemical engineer, and Derik Twomey, a cell biologist, stumbled on the idea. They had experience working with a species of bacteria known as clostridium while developing a biofuel for Cobalt Technologies. After that company closed shop, Mucha set up a lab in her garage to experiment with probiotics and see if she could induce gene transfer in bacteria. It worked. Then the entrepreneurs moved into an incubator, Molecular Sciences Institute in Milpitas, California, to set up a lab. Ten months later they applied to Breakout Labs for $350,000 of seed financing, which gave them matching funds to help secure the CARB-X grant. Now the company is in the midst of getting bridge financing to fund clinical trials and manufacturing.

“This drug development will take time,” Mucha said. “It won’t be ready for FDA drug approval until 2025. But we’re seeing a lot of investor interest in this alternative technology.”

 

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https://www.cnbc.com/2018/10/09/peter-thiel-backs-a-start-up-fighting-the-global-superbug-crisis.html

 

 

 

Researchers Find Artificial Sweeteners Toxic To the Bacteria Found In the Digestive System

Artificial sweeteners commonly used in foods and drinks have a toxic effect on digestive gut microbes.

According to a study published in the journal Molecules, researchers found that six common artificial sweeteners approved by the Food and Drug Administration and 10 sport supplements that contained them were found to be toxic to the digestive gut microbes of mice.

Researchers from Ben-Gurion University of the Negev in Israel and Nanyang Technological University in Singapore tested the toxicity of aspartame, sucralose, saccharine, neotame, advantame, and acesulfame potassium-k. They observed that when exposed to only 1 milligram per milliliter of the artificial sweeteners, the bacteria found in the digestive system became toxic.

“This is further evidence that consumption of artificial sweeteners adversely affects gut microbial activity which can cause a wide range of health issues,” Ariel Kushmaro, a professor in BGU’s department of biotechnology engineering, said in a press release.

According to the study, the gut microbial system “plays a key role in human metabolism,” and artificial sweeteners can “affect host health, such as inducing glucose intolerance.” Additionally, some of the effects of the new FDA-approved sweeteners, such as neotame, are still unknown.

However, the study found that mice treated with the artificial sweetener neotame had different metabolic patterns than those not treated, and several important genes found in the human gut had decreased. Additionally, concentrations of several fatty acids, lipids and cholesterol were higher in mice treated with neotame than in those not.

Because of the widespread use of artificial sweeteners in drinks and foods, many people consume them without knowing it. In addition to being found to be bad for health, some sweeteners have been identified as environmental pollutants. They can also be found in drinking water, researchers noted.

 

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

https://www.usnews.com/news/health-care-news/articles/2018-10-01/study-artificial-sweeteners-toxic-to-digestive-gut-bacteria

New Study Shows that Identifying Patients At Risk For Poor Outcomes Caused by CDI Using Serum Eosinophil Count Information Collected Upon Admission

 

 

 

When it comes to addressing health care-associated infections, Clostridium difficile, remains, well, difficult.

Research suggests that illness due to C difficile is the most common nosocomial infection in the United States, with mortality rates as high as 22%.

Yet, a new study published on September 12 in JAMA Surgery suggests there may be a—relatively—simple and cost-effective solution:

by identifying patients at risk for poor outcomes caused by C difficile infection using serum eosinophil count information collected at hospital admission.

“There’s a frequently obtained, but often underutilized, marker that can predict not only mortality but adverse outcomes in disease,” study co-author David B. Stewart, MD, FACS, FASCRS, associate professor and section chief, colorectal surgery, University of Arizona, told Contagion®.

“Eosinophil count is a marker we often ignore because, in general, it’s relatively unimportant for the bacterial infections we deal with.

However, what our research shows that undetectable levels of eosinophils at the time of admission can be an accurate predictor of disease severity.”

SOURCE:  https://www.contagionlive.com/news/potential-new-marker-for-mortality-due-to-clostridium-difficile-infection

For their research, Dr. Stewart and his colleagues performed a cohort study 2065 adult patients admitted for C difficile infection through the emergency departments of 2 tertiary referral centers over a 10-year period. The study population was then stratified based on eosinophil count (0.0 cells/μL or >0.0 cells/μL) at the time of admission, and divided into a training and validation cohort. The authors used multivariable logistic regression to construct a predictive model for inpatient mortality as well as other disease-related outcomes.

What they found is that of the 2065 patients in the study (52.9% of whom were women; participants had a mean age of 63.4 years), those with an undetectable eosinophil count at admission had increased in-hospital mortality in both the training and validation cohorts. In addition, undetectable eosinophil counts were associated with indicators of severe sepsis “such as admission to monitored care settings, the need for vasopressors, and emergency total colectomy,” according to the authors.

Other significant predictors of C difficile infection mortality at admission included other readily obtainable and easily available markers such as comorbidity burden and lower systolic blood pressures. A subgroup analysis of patients presenting with no initial tachycardia or hypotension revealed that only those with undetectable admission eosinophil counts, but not those with elevated white blood cell counts, “had significantly increased odds of inpatient mortality” due to C difficile infection. In fact, the multivariable logistic analysis revealed that undetectable eosinophil levels (eosinopenia) had greater than 90% accuracy among patients with a predicted probability of mortality of more than 20%.

According to Dr. Stewart, the JAMA Surgery paper is the first human study to follow up on the work of co-author William A. Petri, MD, PhD, Wade Hampton Frost Professor of Medicine and chief, division of infectious disease, University of Virginia, who had explored the relationship between eosinophil levels and C difficile infection mortality in mice.

Given that most emergency departments call for complete blood counts and differentials for every new patient that’s admitted, obtaining eosinophil counts for patients shouldn’t be a costly or inefficient step to take; it would merely entail accessing data that has already been collected, in most cases.

“What we demonstrate in our present study is that eosinophil counts at the time admission are strongly predictive of outcomes with relation to C difficile infection,” Dr. Stewart explained. “Now, we need to look determine, if we were to change the management of patients based on that information, would that change outcomes? [As such,] we are in the planning stages of a prospective clinical trial to see if we can lower the incidence of adverse events like the need for vasopressors and emergency total colectomy by responding to that information.”

In a related commentary published with the study, authors from the department of surgery at McGovern Medical School at the University of Texas Health Science Center in Houston wrote that “admission eosinopenia may be a novel and inexpensive prognosticator for guiding the management of [C difficile infections].

Moreover, there are data to suggest that the resolution of eosinopenia may be a marker for a response to antimicrobial therapy in infections.

Ultimately, interventions to block the TLR2-dependent pathway or to restore eosinophil cell counts may have therapeutic potential in [C difficile infections]

MGB Biopharma (MGB) Prepares To Launch a Phase II Clinical Trial Of Its Anti-bacterial Agent MGB-BP-3

A new drug aimed at treating potentially deadly Clostridium difficile (C. diff) infections is set to be tested on patients for the first time.

Glasgow-based life sciences firm MGB Biopharma (MGB) said it was preparing to launch a Phase II clinical trial of its anti-bacterial agent MGB-BP-3.

The trial is expected to involve 30 patients based in North America.

All have been diagnosed with C.diff-associated disease (CDAD).

C.diff infections can cause diarrhoea and fever.

They have been a major problem in hospitals around the world, with thousands of deaths in the US alone linked to the bug each year.

The bacteria are able to take over the gut when a course of antibiotics kills off the bugs that normally live there.

MGB’s announcement came after it raised £1.3m from investors for trials of the new drug, which was invented at the University of Strathclyde.

The funding round was led by Edinburgh-based Archangels, with co-funding from a range of sources, including the Scottish Investment Bank, Barwell and Melrose-based Tri Capital.

The cash supplements a £2.7m grant awarded earlier this year by Innovate UK.

SOURCE:  https://www.bbc.com/news/uk-scotland-scotland-business-45508036

MGB said its trial would “evaluate safety and tolerability, efficacy and in particular look for improvement in global (or sustained) cure rates”.

Chief executive Dr Miroslav Ravic said: “We are already witnessing renewed interest in our new anti-bacterial agent and its trial in key medical centres in North America where CDAD is particularly prevalent.

“This offers opportunities both to progress the study rapidly and to attract increased attention to the results for this important trial.”

The company said it was aiming to start the trials in areas of the US and Canada with a high incidence of CDAD early next year.

Do You Have A Penicillin Allergy? Fact or Fiction

Are you allergic to penicillin? If so, are you sure about that?

It’s surprisingly common for people to wrongly think they have a penicillin allergy — and that misconception can be dangerous for their health.

Ten percent of all patients in the United States claim to have a penicillin allergy. Of those people, 90 percent are not truly allergic and can tolerate the drug. That means millions of people take alternative antibiotics, which are more expensive and can put their health and potentially the health of others at risk. The solution is a simple allergy test.

A study in the British Medical Journal (BMJ) looked at six years’ worth of medical records for patients in the United Kingdom and found that those with a penicillin allergy had an almost 70 percent greater chance of acquiring a methicillin-resistant Staphylococcus aureus (MRSA) infection and a 26 percent increased risk of Clostridium difficile-related colitis (C. diff.). MRSA and C. diff. are major health risks worldwide. The study compared adults with a known penicillin allergy to similar people without a known penicillin allergy.

People labeled with a penicillin allergy are usually instead given broad-spectrum antibiotics, which may kill off more good bacteria along with the bad. This appeared to increase a patient’s risk of infection with MRSA or C. diff., which are common in our environment and can live without causing any problems on someone’s skin or gut. However, if a broad antibiotic kills off competing good bacteria, MRSA and C. diff. can thrive and start to cause problems.

“Penicillin-related drugs, that whole class … they’re very effective at killing, and they’re very targeted. So for some bacteria they’re still the best. Oldie but goody,” said Kim Blumenthal, lead author of the new study and assistant professor of medicine at Harvard Medical School.

“I have seen so many terrible, terrible outcomes” from C. diff. infections, Blumenthal said, including serious diarrhea, sepsis and death.

“All of us need to understand that antibiotic use is not a free ride, it carries a lot of risk,” said Paul Sax, clinical director of infectious diseases at Brigham and Women’s Hospital. He was not involved in the study but he says the study adds to the “substantial body of evidence” which shows that a penicillin allergy has been linked to longer hospital stays and an increased risk of acquiring resistant infections.

Using non-targeted antibiotics can quickly breed resistant bacteria. “Not only is it harmful to the world and the general population . . . but it’s harmful to the individual patient. So the message to the public is that it could be dangerous to you or me,” said Helen Boucher, director of the Infectious Diseases Fellowship Program at Tufts Medical Center, who was not involved in the study.

“In antibiotic resistance we don’t have a very loud patient advocacy voice . . . and the reasons for that are complicated, but a lot of it has to do with the fact that a lot of the victims aren’t here to speak for themselves because they died,” Boucher said.

The infections are resistant to many known drugs and can quickly become life-threatening. According to the Centers for Disease Control and Prevention, 2 million people, equivalent to the approximate population of Brooklyn, are infected with resistant bacteria every year. At least 23,000 people die each year as a direct result and even more from complications. 

Diagnosing penicillin allergies is challenging. Symptoms such as a rash, nausea or diarrhea could be a sign of allergy, or they might coincidentally occur when someone is taking antibiotics, according to Jonathan Grein, medical director at the Department of Hospital Epidemiology at Cedars Sinai Medical Center in Los Angeles. Children frequently get rashes that are mistaken for penicillin allergies, Blumenthal said.

Even if people are diagnosed correctly as children, they can grow out of an allergy, said Sax.

Which raises the question, what exactly is an allergy? The Internet is full of “answers,” as any late-night Googling hypochondriac can tell you, but an allergy is simply an exaggerated immune response triggered unnecessarily. It can be anything from a rash to trouble breathing.

“Part of the problem is that ‘allergy’ means different things to different people,” said Grein. “Making that distinction between these intolerances and side effects and life-threatening immediate allergic reaction, that’s where the challenge is.”

For example, a patient of Sax’s, in his mid-20s, had a life-threatening heart infection. Penicillin could save him, but his medical record said he was allergic to the drug. Careful questioning by his medical team was able to determine that although he had nausea and diarrhea while on penicillin, he did not have an allergy, Sax said. Knowing this, the hospital administered the appropriate penicillin antibiotic to save his life.

In the case of penicillin, it is important to know that the risks of the allergy diagnosis are sometimes worse than the symptoms of the allergy itself. In most cases, penicillin should only be avoided if the allergy is immediate and life-threatening.

“There are over 30 million Americans who have a penicillin allergy on their record. And there are things we can do,” Blumenthal said.

Examine your own medical record, Blumenthal said. “I would want patients to think, ‘Hmm, am I really allergic to penicillin, or did my mom just tell me and it’s not really true, and should I get that evaluated?’ ”

If it’s been more than 10 years since you were diagnosed, talk to your doctor about getting retested.

Please click on the following link to review the article in its entirety

https://www.washingtonpost.com/news/to-your-health/wp/2018/08/10/most-people-who-think-they-have-a-penicillin-allergy-are-wrong-thats-dangerous/?noredirect=on&utm_term=.47ced452875d

C Diff Foundation’s Health Education Clinic Has Flourished Over Recent Year With the Support From Nursing Students

On Wednesday, August 1st the senior Nursing students from
Rasmussen College attended the Foundation’s
bi-weekly Health Education Clinic in Florida where they were given the opportunity to expand their knowledge base focused on C.difficile (C.diff.)  Infections, Clinical Trials, Sepsis,  and
Antibiotic Stewardship while utilizing their skills with hands on practice.  The students add a new public health topic each month during the Health Education Clinic that benefit the local residents of Pasco County, Florida. The Health Education Clinic began in June 2017 and has proven beneficial to the local citizens to learn more about C.difficile infection prevention, treatments, clinical trials, environmental safety, support, Sepsis, and other leading Healthcare-acquired infections — to name a few MRSA, VRSA.  The Nursing Students, with their clinical faculty member,  introduce topics of hydration, nutrition, diabetes, hypertension, and display their proficiency in blood-pressure monitoring during clinic.

“It has been gratifying to witness the positive changes taking place in the resident’s health over the past year.  We extend our gratitude to the Rasmussen Colleges for incorporating our community program into their student’s curriculum/clinical experience to learn more about our mission from our members and for providing public health educational material to the local community,” stated Nancy Caralla, Founding President of the C Diff Foundation. “The program is mutually beneficial with outstanding results being produced.”

 

 

 

 

 

 

 

 

 

 

 

 

We are grateful for Rasmussen College, and their Nursing Students, for the continued support of this community outreach program.

Veteran Affairs Patients with Recurrent C.difficile Infections Participate In Study

 

 

 

 

Though recurrent Clostridium difficile infections (CDI) are common and pose a major clinical concern, data are lacking regarding mortality among patients who survive their initial CDI and have subsequent recurrences. Risk factors for mortality in patients with recurrent CDI are largely unknown.

Methods

Veterans Affairs patients with a first CDI (positive C. difficile toxin(s) stool sample and ≥ 2 days CDI treatment) were included (2010–2014). Subsequent recurrences were defined as additional CDI episodes ≥ 14 days after the stool test date and within 30 days of end of treatment. A matched (1:4) case-control analysis was conducted using multivariable conditional logistic regression to identify predictors of all-cause mortality within 30 days of the first recurrence.

Results

Crude 30-day all-cause mortality rates were 10.6% for the initial CDI episode, 8.3% for first recurrence, 4.2% for second recurrence, and 5.9% for third recurrence. Among 110 cases and 440 controls six predictors of mortality were identified: use of proton pump inhibitors (PPIs, odds ratio [OR] 3.86, 95% confidence interval [CI] 2.14–6.96), any antibiotic (OR 3.33, 95% CI 1.79–6.17), respiratory failure (OR 8.26, 95% CI 1.71–39.92), congitive dysfunction (OR 2.41, 95% CI 1.02–5.72), nutrition deficiency (OR 2.91, 95% CI 1.37–6.21), and age (OR 1.04, 95% CI 1.01–1.07).

Conclusion

In our national cohort of Veterans, crude mortality decreased by 44% from the initial episode to the third recurrence. Treatment with antibiotics, PPIs, and underlying co-morbidities were important predictors of mortality in recurrent CDI. Our study assists healthcare providers in identifying patients at high risk of death after CDI recurrence.

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https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofy175/5056240