Q&A: Vaccine fails to prevent C. difficile infection but reduces symptom duration
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Key takeaways:
- A vaccine failed to prevent Clostridioides difficile infection in a clinical trial.
- Researchers said that it still may be useful for treatment of CDI.
An experimental vaccine failed to prevent Clostridioides difficile infection in a phase 3 trial but successfully reduced the duration of symptoms, infections requiring medical attention and antibiotic treatments, researchers reported.
Although new treatments for C. difficile infection (CDI), such as fecal microbiota transplantation, have offered clinicians more options, it is still associated with substantial mortality and health care costs, according to the new study, published in Clinical Infectious Diseases.
Donskey and colleagues conducted a phase 3 observer-blinded study that randomly assigned more than 17,000 people aged older than 50 years at increased risk for CDI to receive either three doses of the PF-06425090 vaccine or placebo. The primary endpoint of the study was first CDI episode, and secondary endpoints were CDI duration, need for CDI-related medical attention and antibiotic use.
According to the study, 17 vaccine recipients and 25 placebo recipients had a CDI episode after their third dose (vaccine efficacy [VE] = 31%; 96.4% CI, –38.7% to 66.6%), and 24 vaccine recipients and 34 placebo recipients had a CDI episode after their second dose (VE = 28.6%; 96.4% CI, –28.4% to 61%).
Among participants with a first CDI episode, none of the vaccine recipients sought CDI-related medical attention or required antibiotic treatment compared with 11 placebo recipients needing medical attention and 10 requiring antibiotics.
We asked Curtis J. Donskey, MD, chair of the infection control committee at the Cleveland VA Medical Center, about the trial and whether the vaccine could still potentially be useful, even though it did not effectively prevent CDI.
Healio: How important is it for clinicians to have a tool to prevent or lower risk for CDI?
Donskey: A tool that prevents CDI or reduces the severity of symptoms would be helpful for providers and patients. CDI is associated with 20,000 deaths every year in the United States. It also can result in a substantial negative impact on quality of life for patients and their families. Older adults with multiple recurrences often are fearful of leaving their homes due to uncontrolled episodes of diarrhea or incontinence. Families often struggle to care for debilitated patients with diarrhea, resulting in admission to a hospital or nursing home. Preventing symptomatic infections might also reduce the risk for transmission in hospitals and nursing homes.
Healio: Because the vaccine did not meet its primary endpoint in the trial, do you consider this to be a failure?
Donskey: It was disappointing that the primary endpoint was not met, but I don’t consider the trial to be a failure because the secondary endpoints are clinically meaningful. Reducing the duration and severity of illness can reduce the need to seek medical attention and be treated. Many other vaccines do not completely prevent infections, but they are valuable because they reduce the severity of illness, which can prevent hospitalizations and deaths.
Healio: Although the vaccine did not meet the primary endpoint, there were benefits to patients. Will the vaccine continue to be studied?
Donskey: Pfizer has indicated that it will evaluate next steps for the program in coordination with regulatory agencies.
Healio: What are the takeaways from the study, aside from the vaccine failing to prevent CDI?
Donskey: Clinicians should be aware of the crucial role of the immune system in the pathogenesis of CDI, particularly in recurrent infections. Clinicians should also be aware of the limitations of current testing strategies for CDI.
In the trial, diagnosis of CDI was based on self-reported diarrhea (three or more unformed stools in a 24-hour period) and positive stool tests for both toxin genes and free toxin. The free toxin assay was used because it is more specific for true illness.
However, as is noted in the discussion, asymptomatic carriers sometimes have positive assays for free toxin. Thus, diagnosis of CDI always requires clinical assessment in addition to lab testing. Some patients diagnosed with CDI in the trial may have had diarrhea due to other causes.
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