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, Ellina Degand, Clinical Project Manager, and Christine Tkaczyk, Director of Bacteriology, from our Infectious Disease team discuss the impact of C. diff infections on patients and how AstraZeneca is investigating new ways to prevent recurrence of C. diff infections.
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 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 symptoms 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 C. diff infection, symptoms may include diarrhea, minor cramping and abdominal pain, and they may overcome the infection and recover after appropriate antibiotic 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 C. diff infection die within one month.6
How is C. diff treated and why does it recur?
C. diff infections 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 C. diff infection 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 C. diff infections 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 C. diff infections, 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 C. diff infections and subsequent courses of gut-damaging antibiotics.
Can C. diff infection recurrences be prevented?
Currently, the standard-of-care for recurrence of C. diff infections 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 Infectious Disease 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 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.
Upon spore activation in the gut, C. diff produces toxins that target intestinal cells and gain access into the cytosol where they disrupt critical cellular processes and cause disease symptoms. We’re innovating the use of long-acting monoclonal antibodies that target these key toxins with the potential to protect the intestinal barrier and prevent recurrence of C. diff infection.
How does C. diff impact patients’ lives?
C. diff infections 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.12 Patients can describe themselves as “housebound,” with C. diff infections taking a significant toll on their relationships with family, children and spouses. On top of this, younger patients with an active C. diff infection are impacted professionally. Missing work, struggling with productivity, and worrying about job security only adds to the stress and isolation they experience.12, 13
AstraZeneca is committed to protecting patients from these all-encompassing challenges by innovating solutions that may prevent recurrence of C. diff.
In our conversations with patients, we identified that the C. diff treatment journey frequently follows the below life cycle:
Recurrent C. diff infection can place an additional burden on patients who may already be vulnerable because of underlying health conditions. Preventing recurrence therefore represents an important opportunity to reduce the impact of C. diff infections on patients.
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 illnes.
Our ongoing commitment to C. diff research
We published a narrative review in Infectious Diseases & Therapy, which found that C. diff infection in high-risk patients, including those undergoing stem cell and organ transplants or those living with chronic kidney disease, is associated with increased clinical burden and a negative impact on quality of life.14 Prevention strategies for C. diff infection in these populations are limited, and targeting C. diff with current and future preventive strategies could improve standards of care and reduce impact on patients.14
We’ll continue to leverage insights from patient-centered research as we evaluate innovative approaches to combat C. diff and serious bacterial infections.
