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Nicholas Kitchin, MD, has been working on Pfizer’s Clostridium difficile (C. difficile) vaccine candidate since the first-in-human study was conducted for the vaccine in 2012. Now in Phase 3 trials, he’s experienced the entire journey for the C. difficile vaccine candidate and hopes this vaccine, if the Phase 3 trial is successful and the vaccine is approved, can yield substantial public health benefits globally.

The search for a solution for C. difficile, a potentially recurrent and tormenting infection
Since 2011, Nicholas Kitchin has been part of the Vaccine Clinical Research and Development group at Pfizer. His role as a physician has been to provide medical leadership and oversight, specifically for the Clostridium difficile (C. difficile) vaccine candidate clinical trials. C. difficile infection (CDI) has been recognized by the Centers for Disease Control and Prevention as an urgent public health threat.[1]

C. difficile is a bacterium which can infect the gut, particularly in people who have taken antibiotics.[2] With approximately half a million cases in the United States each year, for example, and a substantial mortality rate – more than one in 11 people over age 65 with CDI die within a month – it requires immediate and aggressive action. [3][4], [5] The development of an investigational vaccine is an exciting endeavour, which Nick feels could lead to a paradigm shift from treatment to prevention if a vaccine is proven effective and licensed.
 
“CDI is a significant unmet medical need as the bacteria are persistent, and can be found in various places, such as hospitals and community and nursing home settings.[1], [6], [7] Therefore, it was a natural target to investigate whether a vaccine could be developed to help prevent it,” explains Nick. “At this time, treatment is problematic and even if the infection is treated, the chances of recurrence are high, which can be tormenting for many who have had a CDI episode.[8]



CDI can be a persistent, debilitating, and potentially deadly disease. The infection can affect anyone, although increasing age, certain chronic medical conditions, and increased contact with healthcare systems put people at greater risk.[5] Many people can have C. difficile bacteria in their gut and stay healthy, but certain people are more likely to develop an infection, including older adults. In fact, nearly two-thirds of all CDIs happen in individuals over 65 years of age.[9] The infection is usually triggered by taking antibiotics, which can disrupt the balance of bacteria in the gut, allowing C. difficile to predominate.[10][11], [12]
 
CDI is also frequently associated with recurrence. Of those who are infected, approximately 25% of people treated will experience a recurrence.[5] The risk of recurrence increases with multiple episodes, and there is an approximately 65% risk of additional recurrence in those with two or more episodes of CDI.[13]
 
“A lot of people are not even aware of C. difficile, and prevention and education often fall on the hospitals to enforce. C. difficile spores can easily spread and are very difficult to inactivate,[14]” warns Nick. “Currently, when it comes to CDI prevention, there is a big focus on infection control through isolation, hand washing, disinfection, and antibiotic stewardship measures.[15] These can be hard to implement and have limited success, making the need for a vaccine even more pertinent.”

Currently, Nick is working on CLOVER (CLOstridium difficile Vaccine Efficacy tRial), the Phase 3 trial for the C. difficile vaccine candidate, spanning 23 countries and enrolling approximately 17,500 participants. This placebo-controlled trial is evaluating the efficacy, safety, and tolerability of Pfizer’s vaccine candidate in adults 50 years of age and older.
 
Through his work, Nick has come into contact with several people who have suffered from C. difficile infection. Several have shared their challenging, sometimes tormenting, personal experiences. Kathy, a former sufferer, had eight disease occurrences over the course of four years. “My experience with C. difficile was agonizing,” explains Kathy. “I felt so isolated, not only because of the symptoms like diarrhea and dehydration, but also because I was had such discomfort that even leaving my house was a challenge.”
 
“I truly believe that a vaccine, if successful in clinical trials and approved by regulatory agencies, has the potential to reduce mortality, morbidity, and healthcare spending, and to hopefully improve people’s quality of life by helping prevent C. difficile infections in the first place,” says Nick. “This potential to shift the way CDI is managed clinically—from treating the symptoms to preventing it entirely—and the impact this could have on public and individual health is a core driver for my personal and career interest in vaccine development. I’ve been working on this vaccine from the very first human trials, and while development of a vaccine continues to be a challenge, we’re exploring novel approaches to try to overcome those challenges.”   

A behaviour shift from CDI treatment to prevention will not come overnight and, in the meantime, education is needed around the dangers of infection and ways people can help to prevent it, like appropriate use of antibiotics and hygiene including proper handwashing. However, there is hope that a vaccine has the potential to bring about significant public health benefits in the future by reducing the burden of C. difficile infection.


[1] Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. Washington, DC: Centers for Disease Control and Prevention; 2013. https://www.cdc.gov/drugresistance/biggest_threats.html#cdiff. Accessed February 12, 2019.
[2] Centers for Disease Control and Prevention. What is C. diff? https://www.cdc.gov/cdiff/what-is.html. Accessed February 28, 2019.
[3] Lessa FC et al. N Engl J Med. 2015;372:825-834.
[4] Centers for Disease Control and Prevention. Nearly Half a Million Americans Suffered from Clostridium difficile Infections in a single year. February 25, 2016. https://www.cdc.gov/media/releases/2015/p0225-clostridium-difficile.html. Accessed February 12, 2019.
[5] Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. Washington, DC: Centers for Disease Control and Prevention; 2013. https://www.cdc.gov/drugresistance/biggest_threats.html#cdiff. Accessed February 12, 2019.
[6] Lessa FC et al. N Engl J Med. 2015;372:825-834.
[7] Lessa FC et. al. Burden of Clostridium difficile Infection in the United States. The New England Journal of Medicine. 2015; 372:825-834.https://www.nejm.org/doi/full/10.1056/NEJMoa1408913
[8] Centers for Disease Control and Prevention. What is C. diff. Updated January 4, 2019. https://www.cdc.gov/cdiff/what-is.html. Accessed February 12, 2019.
[9] Association for Professionals in Infection Control & Epidemiology. Guide to the elimination of Clostridium difficile in healthcare settings 2008.
[10] McFarland LV. Evidence-based review of probiotics for antibiotic-associated diarrhea and Clostridium difficile infections. Anaerobe. 2009;15:274–280.
[11] Bauer MP et al. Lancet. 2011;377:63-73.
[12] Dubberke ER, Wertheimer AI. Review of current literature on the economic burden of Clostridium difficile infection. Infect Control Hosp
Epidemiol. 2009;30:57–66.
[13]Johnson S. Meeting the challenge of recurrent Clostridium difficile infection. J Hosp Med. 2012;7 Suppl 3:S11–3
[14] Viswanathan VK, Mallozzi MJ, Vedantam G. Clostridium difficile infection: An overview of the disease and its pathogenesis, epidemiology and interventions. Gut Microbes. 2010;1(4):234-242. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3023605/
[15] Centers for Disease Control and Prevention. What is C. diff? Updated January 4, 2019. https://www.cdc.gov/cdiff/what-is.html. Accessed February 12, 2019.