Category Archives: Pharmaceuticals

Seres Therapeutics and Nestle’ Health Science Team Up For the Joint Commercialization of Seres Therapeutics Investigational Microbiome Treatment for Recurrent C. difficile Infection (rCDI)

Seres Therapeutics and Nestlé Health Science have announced a decision to team up for the joint commercialization of Seres’s investigational oral microbiome treatment for recurrent Clostridioides difficile (C. difficile) infections (CDI).

Nestlé Health Science had previously received commercial rights to Seres’s therapeutics for inflammatory bowel disease and CDI, but only outside the U.S. and Canada. This expansion places Nestlé as Seres’s global collaborator for SER-109, a therapy the company hopes to treat a leading contributor to hospital-acquired infections in North America. If approved by the U.S. Food and Drug Administration (FDA), the agent, dubbed SER-109, will be the first microbiome therapeutic available.

Each year, CDI contributes to the deaths of 20,000 Americans. Standard of care for recurrent CDI includes the use of fecal microbial transplants. Currently, there is no microbiome therapies approved for any indications, which has created an unmet need recognized by an ever-growing list of pharmaceutical companies partnering with microbiome startups.

Seres’s investigational SER-109 includes purified Firmicutes spores; the rationale for including these spores is “based on their modulatory role in the life cycle of C. difficile and disease pathogenesis,” according to a statement made by the company.

Findings from the pivotal Phase III ECOSPOR III trial announced back in August 2020 showed SER-109 significantly reduced the CDI recurrence rate compared with placebo over an eight-week period. The absolute reduction of the CDI recurrence rate was 27% while the relative risk reduction was 68%. In addition, up to 88% of patients experienced a sustained clinical response by the end of the eight weeks.

Nestlé Health Science has agreed to use Aimmune Therapeutics, the company’s global pharmaceutical business, to lead the commercialization of the therapy. In return, Seres has agreed to receive upfront licensing payments totaling $175 million. An additional $125 million will be paid to Seres by Nestlé upon FDA approval of the microbiome agent.

Under terms of the agreement, Seres holds the sole responsibility for costs associated with development and pre-commercialization of SER-109 in the U.S. The company will be eligible to receive up to 50% of the commercial profits once the therapeutic is commercialized.

“Nestlé Health Science has been a terrific collaborator in our quest to develop a new treatment option for patients suffering from recurrent C. difficile infection, and their support over the past few years has been critical in advancing SER-109 to address this unmet need,” said Eric Shaff, Seres Therapeutics’ chief executive officer, in a statement. “As we prepare for potential approval and commercialization, we are eager to embark side-by-side on our next phase with a company that believes as fervently as we do in the potential of this transformative approach to reduce the recurrence of CDI.”

Nestlé Health Science’s CEO, Greg Behar, added that the company “is focused on the fast-developing areas of gut health, food allergies and metabolic health within our global pharmaceutical business, Aimmune Therapeutics.” As such, Aimmune’s “fully integrated commercial infrastructure” will be leveraged to launch the therapy, pending approval.

Seres has been busy this year in moving its investigational microbiome therapy pipeline in front of the FDA. Last month, Seres announced the agency had cleared an Investigational New Drug application for the company’s other investigational microbiome therapeutic for preventing antibiotic-resistant bacterial infections as well as graft-versus-host disease.

The company is advancing SER-155 into a Phase Ib trial under a collaboration with Memorial Sloan Kettering Cancer Center. “SER-155 represents a novel microbiome technology with the potential to address antibiotic-resistant bacterial bloodstream infections and further to modulate host immunomodulatory responses to decrease graft-versus-host disease,” said Seres’s chief scientific officer, Matthew Henn, Ph.D., in a statement.

 

SOURCE:  https://www.biospace.com/article/seres-nestle-agree-to-jointly-commercialize-microbiome-agent-for-c-diff-infections/

IDSA, SHEA Update ADULT C. difficile Infection (CDI) Treatment Guidelines

“The panel’s recommendations for the management of CDI are based upon evidence derived from topic-specific systematic literature reviews,” Stuart Johnson, MD, infectious disease clinician and researcher at the Edward Hines Jr. Veterans Administration Hospital, and colleagues wrote.

The new guidance for CDI management in adults is as follows:

  • For patients with an initial C. difficile episode, fidaxomicin is recommended rather than a standard course of vancomycin.
  • For patients with recurrent C. difficile episodes, a standard or extended-pulsed regimen of fidaxomicin should be used rather than a standard course of vancomycin.
  • For patients with a recurrent C. difficile episode within the past 6 months, bezlotoxumab and standard-of-care antibiotics should be used rather than standard-of-care antibiotics alone.

“Head-to-head trials of differing anti-CDI recurrence strategies using narrow-spectrum antibiotics that target C. difficile, restoration of the microbiome using biotherapeutics or [fecal microbiota transplantation], or augmentation of the host immune response with agents such as bezlotoxumab given alone or in combination (eg, in combination with fidaxomicin) are needed,” the authors wrote.

 

SOURCE:  https://www.healio.com/news/infectious-disease/20210624/idsa-shea-update-guidance-for-managing-patients-with-c-difficile

Proton-Pump Inhibitors and Increased Risk of C. diff. Infections

 

 

 

 

 

Increased risk for Clostridium difficile (C diff) infection remained elevated for up to a year after the conclusion of treatment with proton-pump inhibitors (PPIs), according to a paper published in Clinical Infectious Diseases.

Malin Inghammar, PhD

Source and to read the article in its entirety please click on the following link to be redirected:

https://www.hcplive.com/view/elevated-risk-c-diff-proton-pump-inhibitor-use

Investigators from Copenhagen, Denmark used a nationwide cohort of adults with
a C diff infection in order to compare periods with and without exposure to PPIs. The adults were all treated between February 2010 and December 2013. The nationwide database included health information such as C diff testing, filled prescriptions, and patient characteristics. The investigators also accounted for the previous hospitalization in the previous 12 weeks in the patients, in addition to chronic disease, genetics, socioeconomic status, length of hospital stay, and antibiotic and corticosteroid use.

Ultimately, the study authors identified 3583 episodes of community-acquired C diff infection, of which 964 occurred during the current use of PPIs. This is an observation in the current literature, but what wasn’t understood was the full extent of the relationship due to missing data from randomized controlled trials, variability between studies, and insufficient adjustment for confounding.

“While a history of prior hospital admission, advanced age, and antibiotic use are well-known risk factors for C diff infection, the role of PPIs has remained controversial,” the study authors wrote.

The investigators defined new PPI use as a new prescription for individuals who had not used PPI in the prior 365 days. They split up the periods of 0-6 months and 6-12 months because in the first period, cessation was considered indeterminate use because of the possibility for intermittent use or drug exposure continuing beyond the use period. Exposure during the 6-12 month period was “unlikely.”

Of the infections that occurred with the use of PPIs, 324 occurred within 0-6 months after treatment conclusion. Additionally, 123 cases occurred between 6 and 12 months after treatment cessation.

The remainder of C diff infection cases occurred during time periods without use of PPIs, the investigators said.

Comparing the use of PPIs with nonuse, the study authors found that the adjusted estimate incidence rate ratio (IRR) was 2.03, they said. But the risk remained elevated in later time periods too: 1.54 for 0-6 months and 1.24 for 6-12 months.

“In conclusion, in this nationwide study in Denmark, we showed that exposure to PPIs was associated with a moderate increase in the risk of community-acquired C diff infection,” the study authors said while noting that the mechanism by which PPIs may increase the C diff infection risk remains unclear. “The increased risk was most prominent during current PPI use but also persisted after treatment discontinuation.”

One limitation the study authors provided for was that initial symptoms of C diff infection could have been misinterpreted and patients prescribed PPIs could not be excluded. But, they also admitted, “it is unlikely that this would lead to biased results because the symptoms of C diff infection (diarrhea) are distinct from the upper gastrointestinal symptoms that represent the most common indication for PPIs.”

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

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.  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