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1rem

“Usually for antibiotic awareness you have a week,” said Dr. Teena Chopra, “But for 

a whole month has been dedicated, for a reason.”

Awareness Month and Antimicrobial Awareness Week. As Chopra explains, too often the people most affected by a lack of vigilance in these areas already experience marginalization and discrimination.

“We are all global citizens, and having that uniform, consistent health care for all is where we need to move toward,” said Chopra.

Teena Chopra, MD, MPH is the Corporate Medical Director of Hospital Epidemiology at Detroit Medical Center, as well as a professor at the Wayne State University School of Medicine.

Chopra credits several mentors as inspiring her to specialize in infectious disease. Living and working in Detroit, MI, she has seen firsthand how infectious diseases can ravage underserved populations, moving her to practice where she’s most needed.

causes an estimated half a million infections a year and over a billion dollars in expenses in the US alone.

The Centers for Disease Control and Prevention (CDC) classifies 

However, until the disease touches their lives, the general public is largely unaware of its prevalence or even what 

 is. “We, as the health care community, need to raise more awareness for 

Listen in as Chopra discusses treatment regimens for 

 infection (CDI), as well as the populations disproportionately affected by this debilitating disease.

Missed Episode 6 of Contagion Community? 

Listen in on the conversation and feel free to offer your feedback on this episode, interest in participating in the podcast, or suggest ideas for future episodes. Please email your correspondence to Nina Cosdon: 

Dr. Teena Chopra discusses the global need to do more to prevent healthcare-associated infections like C difficile in vulnerable patient populations.

C difficile, Antimicrobials, and the Patients Most Affected

Nature Medicine published additional data on Vedanta Biosciences’ Clostridioides difficile investigational therapy, VE303, from its phase 2 trial.

Investigational Live Biotherapeutic Product Significantly Reduces Risk of Recurrent Clostridioides difficile 

CEO Larry D Sutton, MD, PhD, elaborates on the company's strategy and the science behind SIDIPREV to prevent C difficile infections in hospitalized patients.

LPOXY Therapeutics Acquires Assets to Advance C difficile Protection for Antibiotic Patients

Here are some of the bigger stories on this topic from this year.

Contagion's 2024 Top Stories: C difficile

Investigators at the University of Virginia are examining the potential link between the “sympathetic” nervous system and the role of the seriousness of the infection.  

Could the Flight or Fight Response Trigger Severe C difficile?

This week, recent studies show progress in healthcare, including an mRNA vaccine for C difficile, the rise of antimicrobial resistance, peer-assisted telemedicine for hepatitis C in rural areas, and more.

Targeting C difficile with Oxygen-Based Therapy

LPOXY Therapeutics, Inc has acquired key assets from Xeno Biosciences Inc to advance its therapy, SIDIPREV, aimed at preventing 

) infections in hospitalized patients. The acquisition includes regulatory filings, FDA correspondence, CMC data, intellectual property, and Phase I and Ib clinical trial data confirming the safety of the active pharmaceutical ingredient. This acquisition enables LPOXY to initiate a Phase II study of SIDIPREV under the FDA’s Limited Population Pathway for Antibacterial and Antifungal Development (LPAD).

In our recent conversation with Larry Sutton, MD, PhD, CEO of LPOXY Therapeutics, he discussed the significant impact of 

 infections, which cause over 30,000 deaths annually in the US, Sutton explained, 

C difficile is an anaerobic pathogen… it doesn't like oxygen, they can't detoxify oxygen, and they get sick from it.

 particularly susceptible to oxygen, which has been shown to inhibit its growth and suppress the production of toxins that cause disease. As Sutton elaborated, 

What oxygen does is it inhibits its growth and suppresses toxins production that causes disease.

In addition to its antibacterial effects, oxygen has been demonstrated to have anti-inflammatory properties, which could be beneficial for healing the gut and preventing infections. Sutton further noted, “Oxygen is an anti-inflammatory in the gut. So it can help the healing in that way as well.” This antimicrobial and anti-inflammatory dual effect supports the potential for oxygen-based therapies in treating gastrointestinal conditions.

One of the challenges with current oxygen delivery methods, such as hyperbaric oxygen therapy, is that they are cumbersome and not suitable for widespread use. Sutton pointed out, “All these other data that are out there in the academic literature administer oxygen through cumbersome and uncomfortable methods… however, an oral administration will.” Oral oxygen administration could provide a more practical and scalable solution, especially for patients with inflammatory bowel diseases like ulcerative colitis, for which current treatments are limited.

Looking ahead, LPOXY is focused on exploring oral oxygen delivery as a promising approach for preventing 

 infections and treating various inflammatory bowel diseases. Sutton highlighted, “There is a lot of data out there that oxygen is beneficial in inflammatory bowel disease, especially ulcerative colitis.” This emerging therapy could help address significant unmet needs in treating these challenging conditions.

LPOXY Therapeutics, Inc. Acquires Key Assets from Xeno Biosciences Inc. to Advance C difficile Prevention Therapy. January 4, 2024. Accessed January 13, 2024. 

https://firstwordpharma.com/story/5925021

Larry Sutton, MD, PhD, discussed how oxygen affects C. difficile and provides anti-inflammatory effects in the gut, with potential applications for gastrointestinal diseases.

Joseph Zackular, PhD suggests that mRNA vaccines and monoclonal antibodies could offer more effective treatments for recurrent C difficile infections

Targeting the C Diff Pathogen and Its Immune-Suppressing Toxins

In the next part of our conversation with Joseph Zackular, PhD the discussion centered on 

 infections, the impact of antibiotics on the microbiome, and emerging approaches to treatment, including vaccines and monoclonal antibodies. One of the key takeaways is the potential of vaccination to prevent severe disease, even in recurrent infections, by overcoming the immune-suppressing effects of 

As Zackular explains, antibiotics, which are the primary treatment for 

, also disrupt the very microbiome that normally protects against the pathogen. This creates a paradox where the treatment itself increases susceptibility to infection:

“When we think about recurrent and relapsing infections, that’s a big problem with 

 is perturbation of your normal, healthy microbiome, which normally confers resistance to this pathogen. The main risk factor is antibiotics. So when you perturb this community, it becomes susceptible to 

. But there’s this paradox where the way we treat 

 is antibiotics, which is the thing that makes you susceptible to 

.” This paradox creates a cycle where patients suffering from recurrent 

infections are caught in a loop of antibiotic use, gut microbiome disruption, and persistent vulnerability to the infection.

 is so difficult to treat lies in the way the bacteria’s toxins interact with the immune system. When a person becomes infected, 

 releases toxins that damage the gut lining, leading to the characteristic symptoms of the infection, diarrhea, fever, and abdominal pain. These toxins also have a more insidious effect: they suppress the body’s adaptive immune response, making it harder for the immune system to respond effectively.

, the toxins actually stunt adaptive immune responses to themselves,” said Zackular. “The toxins don’t just go after the barrier itself but can translocate and impact immune cells that are critical for responding to the infection.”

This suppression of the immune system is one reason why 

 infections tend to recur in certain patients. Their immune systems are effectively “hobbled” by the very toxins produced by the bacteria, preventing a full immune response. Zackular’s research has shown that a targeted vaccine could help reverse this immune suppression, potentially preventing recurrence.

“We were able to show that if you vaccinate after infection, you can overcome that stunting of the toxins on the immune system. This is important because people who suffer from recurrent infections aren’t getting help from their immune system. By vaccinating after the initial infection, we might be able to repair that stunted immune response and give the gut’s microbiome some help from the immune system.”

Historical vaccine attempts failed because they targeted only the toxins rather than the pathogen itself. mRNA vaccines offer a promising solution, addressing toxins and the pathogen while also providing flexibility to adapt to emerging strains. 

“There have been several vaccines that showed early promise but ultimately failed in phase three clinical trials. These vaccines targeted the toxins 

 produces two potent toxins that drive the disease. But just targeting the toxins and providing immunity to them might not be enough,” explained Zackular. “We found that focusing only on the toxins with protein-based vaccines didn’t provide the protection we had hoped.”

The emergence of mRNA vaccine technology, which has shown success in combating other infectious diseases like COVID-19, provides new hope for 

 treatment. Unlike traditional protein-based vaccines, mRNA vaccines can be designed to target both the toxins and the pathogen itself. Additionally, mRNA platforms are highly adaptable, making them capable of addressing new and emerging strains of 

“The mRNA vaccine platform has real potential,” said Zackular. “We can target the toxins like previous vaccines did, but we can also make it multivalent and target other aspects of this complex system. This could help overcome some of the limitations of the initial vaccines.” This multivalent approach allows for broader protection and may offer a more effective way to address the complexities of 

While monoclonal antibodies are valuable tools, Zackular emphasized the need for a combined approach, one that includes both vaccines and antibody treatments to effectively combat the infection.

“An FDA-approved monoclonal antibody called bezlotoxumab from Merck can be given to patients and has shown to be relatively effective. We know there is promise here, but we still need to develop the right vaccine platform with high immunogenicity, like potent mRNA vaccines, to address the complexity of the infection and the emergence of new strains,” he noted.

 strains is an ongoing challenge. New strains are emerging, not only in healthcare settings but also in the community, further complicating treatment. Zackular believes that mRNA vaccines offer the flexibility needed to adapt to this evolving landscape.

“We’re starting to see all different types of strains of 

 circulating across the globe, as well as the emergence of community-associated 

 infections, which are driven by a variety of 

 strains. The flexibility of mRNA vaccines gives us hope that we can adjust vaccines quickly for what we’re seeing in patients.” This adaptability could be important for staying ahead of new strains and ensuring that treatments remain effective over time.

Tune in for part 3 of our interview tomorrow on how hospital-acquired infections have decreased, community-acquired cases have risen, complicating targeting for prophylactic vaccination, and more.

Joseph Zackular, PhD suggests that mRNA vaccines and monoclonal antibodies could offer more effective treatments for recurrent C difficile infections


Joseph Zackular, PhD, shares insights on his team’s mRNA vaccine research for C. difficile, highlighting progress in animal models and future plans for human trials.

mRNA Vaccine Shows Potential for C difficile Infections

Joseph Zackular, PhD, an assistant professor at the Children's Hospital of Philadelphia and the University of Pennsylvania, is leading research on 

) and the development of an mRNA vaccine. His recent work has shown promise in reducing mortality and improving outcomes for infections caused by this bacterium.

In our recent interview, Zackular discussed how his team used animal models, including mice and non-human primates, to test the vaccine's safety, immunogenicity, and efficacy. 

 has long posed a major public health threat due to its ability to form spores that survive harsh environments, making treatment difficult. Zackular believes the mRNA vaccine could help address this persistent infection, especially for patients with recurrent cases.

The current study builds on promising results from animal models, including mice, where the vaccine showed encouraging efficacy. When asked about the transition from animal to human trials, Zackular emphasized the importance of animal models in understanding immune response, vaccine efficacy, and safety.

“To start with, animal models that recapitulate what we see in humans, so that we can study the immune response, the efficacy of, you know, treatments like vaccines, you know. So ultimately, thinking about safety, thinking about immunogenicity, thinking about the effectiveness of these strategies for taking on a challenging infection like 

," Zackular explained. He further noted that while animal models are valuable, the ultimate goal is to bring these therapies, particularly vaccines, to human trials.

"Our work in animal models was by design using physiologically relevant concentrations of these mRNA vaccines that would be safe for humans, validated by the work done with the COVID-19 vaccines. What we’re working towards now is using other animal models, like hamsters and non-human primates, to assess immunogenicity and safety, and ultimately bring this to phase one clinical trials to evaluate efficacy and safety in humans,” he said.

Zackular is hopeful that results from animal models will be replicated in humans, providing an important tool for addressing 

 is known for its ability to oscillate between a vegetative cell state and a dormant spore form, making it extremely difficult to eliminate. The pathogen's lifecycle, which includes toxin production and spore formation, complicates treatment and prevention efforts.

 is a really challenging and uniquely challenging pathogen for us to take on. It lives a really complex life cycle, and so, 

 is a vegetative cell, so a bacterium that produces two really potent toxins that cause disease, but 

 also makes a spore, and this spore is really, really hard to kill and survive outside of the body, but even when it’s inside the body, it can be really challenging for antibiotics to kill, can be challenging for our own immune systems to kill," Zackular explained.

Despite these challenges, the vaccine developed in his lab has shown the potential to reduce the severity of disease. While it has not yet prevented the initial colonization of 

 in animal models, the vaccine significantly reduced mortality and improved outcomes.

 from being able to colonize and cause infection, but that’s challenging. It's an organism that lives in this relatively hard-to-get-to part of our body, the lumen of the gut, and it doesn’t invade. And so being able to prevent it from colonizing, of course, can be challenging,” Zackular said.

In studies with a highly virulent strain of 

, the vaccine prevented 100% of mortality in mice, which is a remarkable outcome. “What we found is that we aren’t able to prevent the initial colonization and outgrowth of this pathogen. However, we are able to find that we can dramatically stunt the pathogenicity and the disease that's caused by this really problematic infection,” he added.

This vaccine uses the mRNA platform, which has already proven successful in COVID-19 vaccines. Zackular's team has developed a tetravalent vaccine targeting both toxins responsible for 

’s harmful effects and the bacterial cell and spores.

“This mRNA vaccine platform allows us to create multivalent vaccines very readily. And so what we’re able to do in this paper was make a tetravalent vaccine that targets both of the really important toxins that cause disease with 

, but also target the cell itself as well as the spore,” Zackular explained.

The research represents a promising proof of principle that mRNA vaccines could be effective in preventing 

 disease. Looking forward, the team hopes to further refine the vaccine, targeting more virulence factors and potentially preventing initial infection or promoting quicker bacterial clearance.

“Ultimately, in the future, we’re hopeful that we can add even more targets against the cell, against the spore, against other virulence factors that might allow us to prevent initial infection, or at least clear even quicker,” Zackular said.

Stay tuned for part 2 of our interview where we discussed the complexities of 

 infections, often recurrent due to antibiotic-induced disruption of the gut microbiome and more.

Joseph Zackular, PhD, shares insights on his team’s mRNA vaccine research for C difficile, highlighting progress in animal models and future plans for human trials.

 Paul Feuerstadt, MD, FACG, AGAF, discusses what the data says as well as offers insights about what patients can expect and medical peer-to-peer information about the procedure. 

Two Years FDA Approved, Rebyota Continues to Show Efficacy and Safety

It has been 2 years this month since fecal microbiota, live – jslm (Rebyota) was FDA approved for the indication of recurrent 

 treatment in individuals 18 years of age and older, following antibiotic treatment for recurrent 

New data was released at this year’s ID Week showing its continued efficacy and safety 2 years after the approval. Ferring Pharmaceuticals announced results of its outpatient real-world study using Rebyota. 

In one of the analysis, investigators reviewed the medical records of 64 adult patients from 32 physician offices nationally who received Rebyota from February 2023 to March 2024. In total, 59 patients completed the 8-week follow-up period, of which 75% (n=44) had no CDI recurrence. There were no adverse events reported with treatment aside from minor leakage during administration in 4 patients (6.2%).

Participants in the analysis had a median age of 75 years and were predominantly female (65.6%). Patients had multiple comorbidities (Charlson score 4.5) and 59.4% had 2 or more rCDI risk factors, the most common being age, 65 years or older (75%), and concurrent use of gastric acid suppressants (59.4%). The median number of prior CDI episodes was 3. Fidaxomicin (57.8%) was the most utilized standard-of-care antibiotic for treatment of CDI prior to Rebyota administration.

Additionally there has been other data being released from the PUNCH CD3 trial.

“The open label study data that was published earlier in 2024, which was the largest study that looked at live biotherapeutic products, looked at 697 total patients, so a massive group expanding upon the PUNCH CD3 trial—the randomized control trial that had a placebo arm within this open label study,” said Paul Feuerstadt, MD, FACG, AGAF an associate clinical professor of medicine at the Yale School of Medicine. “Patients with IBS are going to show up in a provider's office with their current 

. Patients with ulcerative colitis and Crohn's disease are also going to show up in providers offices' with 

 so how does this work in a real world type scenario? And across those 697 patients, they found an efficacy of 73.8% further validating the randomized control trial from phase 3. And of those 73.8%, 91% remained responsive at 6 months. So in a real world, formalized study setting, we see very, very encouraging data.”

Feuerstadt also says in his conversations with patients he explains the differences from taking antibiotics and getting this treatment. 

“If we explain it appropriately, the patients will understand that the antibiotic controls the phase that causes symptoms, but that spore phase, the phase that remains in their system after the antibiotics that requires a healthy, diverse microbiota, and that regrowth of the microbiota without supplementation causes a recurrence. Therefore, if you're putting the microorganisms into the place where the infection is, you're preventing that recurrence. So patients can wrap their head around that concept and understand how you're treating the entire infection and how you're shutting down that cycle of recurrence. And that clicks in their head, where they have that aha moment,” Feuerstadt said.

Paul Feuerstadt, MD, FACG, AGAF, discusses what the data says as well as offers insights about what patients can expect and medical peer-to-peer information about the procedure. 

C. Difficile

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