ORIGINALLY PUBLISHED
02 December 2024
Clostridioides difficile, or C. diff, is a bacterium that can cause severe diarrhea and intestinal inflammation that may be life-threatening. Stacey Cromer Berman, Global Product Lead, Catia Ferreira, Senior Global Medical Affairs Leader, and Christine Tkaczyk, Director of Bacteriology, from our Vaccines & Immune Therapies team discuss the impact of C. diff infections (CDIs) on patients and how AstraZeneca is investigating new ways to prevent serious disease.
How common is C. diff and who is at risk?
C. diff is one of the leading causes of healthcare-associated infections in the U.S., with approximately 500,000 infections diagnosed each year.1-3
People are most at-risk for contracting a C. diff infection (CDI) when they are prescribed antibiotics to treat or prevent another bacterial infection.1 Antibiotics treat infections by killing or preventing the growth of disease-causing bacteria, but they can also deplete the beneficial (“commensal”) bacteria in the gut microbiome that shield the body from harmful infections, like C. diff.1
When C. diff spores, an inactive and protected form of the bacteria found in the environment or stool, are ingested, they germinate, or become active, in the intestines.1 Individuals with a healthy gut microbiome generally do not develop an infection even when the spores reach their intestines. However, in those with a disrupted gut microbiome, such as a person who has recently taken antibiotics, C. diff spores may colonize the intestinal tract, leading to growth and proliferation of the bacteria and, ultimately, the production of symptom causing toxins.1
While C. diff can be transmitted to anyone, older adults, people who recently stayed at a hospital or nursing home and those with weakened immune systems, such as organ transplant patients taking immunosuppressive drugs or people with cancer are at higher risk of developing the infection.4
For people with a mild to moderate CDI, symptoms may include diarrhea, minor cramping and tenderness, and they may overcome the infection and recover after a few days with treatment.5 However, older adults and people with weakened immune systems are especially vulnerable to suffering from severe outcomes, which could include, severe colitis, colon perforation that may require surgery or removal, and death.6,7 In fact, it is estimated that 1 in 11 people over the age of 65 who are diagnosed with a healthcare-associated CDI die within one month.6
How is C. diff treated and why does it recur?
CDIs are usually treated with antibiotics, and while the infection clears initially, there is a risk of recurrence after treatment due to regeneration of antibiotic tolerant spores formed by the bacteria.1,7 About 1 in 6 patients who get a CDI will experience a recurrence within 8 weeks – some within days – and their risk of recurrent infections gets progressively worse after each episode.1,8
While potential effective treatments are available against C. diff, the commonly prescribed antibiotics used to treat CDIs also disrupt the microbiome and create an environment where colonized C. diff thrives and can proliferate easily.1,4 This results in some patients requiring repeated courses of antibiotics to control the recurrent infections which increasingly disrupts the microbiome, leading to an intensive cycle and contributing to the increased risk of recurrence of C. diff.1,4
Antibiotics can be very effective at treating active CDIs, but unfortunately, they also have impact on the microbiome which make patients more susceptible to recurrences. We are taking a different, microbiome-sparing approach and focusing on prevention early in the treatment pathway, with the goal of prevention of recurrence of CDIs and subsequent courses of gut-damaging antibiotics.
Can CDI recurrences be prevented?
Currently, the standard-of-care for recurrent CDIs is antibiotic treatment but there are some emerging strategies focused on prevention.1,9 When antibiotics alone fail to resolve the cycle of infection, an alternate strategy used to address the disruption to the microbiome is microbiota-based live biotherapeutic products (LBPs), which may be used to restore the balance in the microbiome and prevent the recurrence of C. diff.10 LBPs are still being explored to determine the optimal composition of microorganisms as well as the ideal patient populations.10
Our Vaccines & Immune Therapies team is “following the science” by exploring the potential use of long-acting bacterial monoclonal antibodies (mAbs) targeting specific toxins, also known as virulence factors, expressed by bacterial pathogens, like C. diff. 11 This approach has the potential to be preserve the microbiome while targeting the root cause of the infection, and may reduce the need for repeated rounds of antibiotics and which could offer protection against symptomatic disease recurrence.12
Upon spore activation in the gut, C. diff produces toxins that target intestinal cells and move into their cytoplasm where they disrupt cellular functions and cause disease symptoms. We’re innovating the use of long-acting bacterial monoclonal antibodies that target these key toxins and may protect the intestinal barrier and prevent recurrent C. diff disease.
How does C. diff impact patients’ lives?
CDIs can have a significant and debilitating impact —physically, psychologically, economically, and emotionally. While the active infection itself is painful and disruptive, many patients are impacted long-term due to fear and anxiety of recurrence. Patients can describe themselves as “housebound,” with CDIs taking a significant toll on their relationships with family, children and spouses. On top of this, younger patients with an active CDI are impacted professionally. Missing work, struggling with productivity, and worrying about job security only adds to the stress and isolation they experience.13,14
AstraZeneca is committed to protecting patients from these all-encompassing challenges by innovating solutions that may prevent reinfection of C. diff.
C. diff has significant personal and public health burdens, especially for the patients with existing illnesses like cancer, renal or autoimmune disease. By focusing on the prevention of serious disease caused by recurrent C. diff, we're working toward the goal of protecting the patients that AstraZeneca serves and reducing the impact of this common but serious bacterial infection over the course of a person's lifetime.
When I first started getting sick with C. diff I kept telling myself, it will be fine soon. I'm not going to get this again soon. It'll be done. Now, more than ten years in, I understand that this is a disease that could plague me for the rest of my life. My hope for the future is that we'll all be aware of this disease and we'll all be working to find ways to prevent and acutely treat this illness
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