Category Archives: C. diff. Research Community

Dr. Michael Pride, a Pfizer Scientist, Leads a Team Searching For Ways to Improve Diagnosis, Prevention and Treatment of Clostridium difficile Infections

Dr. Pride of Pfizer leads a team that is searching for ways to improve diagnoses & treatment of C. difficile,

Dr. Michael Pride is the Executive Director, Vaccine Research and Development at Pfizer

Challenges, Chance and Looking Forward. Historically, a difficult diagnosis process has posed challenges to treatment for C. difficile infections, as detection is not straightforward. Dr. Pride and his team are working to tackle this issue by developing better ways to diagnose this infection, which will aid efforts to develop a vaccine. Additionally, he is encouraged by recent work that has demonstrated how an antibody can help prevent recurrent diseases, offering insight that an antibody-mediated response, raised by vaccines, may be a way to help reduce a primary episode of a C. difficile infection.

“If our vaccine is successful, we could help have a great impact on global health, reducing morbidity and even mortality worldwide,” he says. “I’m confident in our team, who is working tirelessly so that hopefully no one must suffer from these horrible symptoms again.”

Today, Dr. Pride leads a team of scientists responsible for the development, qualification and validation of various assays that support Pfizer’s vaccine programs.

 

 

Click on the link below to learn more about Dr. Michael Pride’s Work:

http://innovation.org/about-us/innovation-faces/researcher-profiles/michaelpride?utm_source=Twitter&utm_medium=Social&utm_campaign=NCAC&utm_term=02030501050201&utm_content=DrMichaelPride&sf200705754=1

 

Study Finds Factors That May Help Predict Which Patients Are More Likely to Develop a CDI

A cluster of factors may help predict
which patients are likely to develop Clostridium difficile
infection, a new study has found. And that could help
in efforts to prevent infection, according to the researchers.

Reduced immune function, recent antibiotic use, current or recent hospitalization and prior C. difficile infection predicted risk of subsequent infection, opening the door to potential preventive interventions.

“This could help healthcare providers red-flag those patients who are at high risk of C. diff, and may one day lead to therapeutic or dietary tactics to lower the chances of infection,” said the study’s co-lead author, Vanessa Hale of Ohio State University.

The study appears in the journal Science Translational Medicine.

The research included studies in both humans and mice, and involved the transplant of feces from human study participants to mice to assess differences in susceptibility to
C. difficile infection and molecular-level explanations for that increased risk.

“Microbes in the gut play a critical role in defending against disease, and the really exciting part of this study is that it might help us better identify the risk factors that are linked to problems in the gut and susceptibility to these dangerous infections,” said Hale, an assistant professor of veterinary preventive medicine at Ohio State. The study was conducted at the Mayo Clinic, where she previously worked.

The researchers started by looking at the gut microbes of a group of 115 people who had diarrhea but who did not have C. diff when they first sought medical care, some of whom went on to develop a C. diff infection. They also analyzed the gut microbes of 118 healthy volunteers for comparison.

“About half of the diarrhea patients had gut microbial communities that looked healthy, but the guts of the other half were really intriguing – they had different microbes and very different levels of metabolites. We called this half the ‘dysbiotic’ – or unhealthy – group,” Hale said.

“When we transplanted human stool from the dysbiotic group into mice, we discovered that these mice were more likely to become infected with C. diff than mice that received human stool from the healthy-looking group.”

The researchers then examined potential risk factors found on the medical charts of individuals with “dysbiotic” and healthy-looking gut microbial communities and found a cluster of five factors that were associated with unhealthy communities.

“We knew that dysbiotic microbial communities put mice at higher risk of C. diff infection, and we wanted to see if the five factors could be used to predict C. diff infections in humans,” Hale said.

To do this, the research team went back and looked at the medical charts of more than 17,000 previous patients who were free of C. diff when they initially sought care. In that larger group, there also was a clear connection between the risk factors and subsequent C. diff infection.

Furthermore, the researchers found higher levels of amino acids – particularly proline – in the guts of mice that received transplants from people whose gut microbiomes were unhealthy, or dysbiotic.

That was interesting, and potentially important, because C. diff needs amino acids like proline to proliferate and it cannot make proline on its own. That prompted the team to wonder if reducing dietary amino acids could protect against C. diff, Hale said.

Feeding the mice diets low in protein moderately lowered the growth of C. diff, providing further evidence that amino acids – including proline – play a role in risk of infection and leaving researchers curious about the potential for dietary interventions in at-risk humans, Hale said.

“It’s possible that a dietary strategy could reduce C. diff infection in those patients who are deemed to be susceptible based on the cluster of risk factors we identified,” she said, adding that more study is needed to understand that relationship.

The study also showed that prophylactic fecal transplantation from a healthy donor could protect against C. diff in mice that were initially prone to infection.

“The transplants were fully protective against C. diff infection in all of the animals we tested, which was pretty amazing,” Hale said.

………………………It is unlikely that fecal transplantation would quickly be adopted as a prevention strategy in those deemed to be at elevated risk of infection, Hale said.

 

The National Institutes of Health and the Center for Individualized Medicine at Mayo Clinic supported the study.

Eric Battaglioli of Georgetown College was the co-lead author. Purna Kashyap of Mayo Clinic is the senior author.

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

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.

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

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