C. difficile infection: A close-up on an urgent public health threat

Over the past two years, the world has focused intensely on one infectious disease, COVID-19. Yet, as hospitals have dealt with surging admissions and extended stays, staff and patients alike have still had to contend with another potentially deadly infection from a bacterium called Clostridioides difficile (C. difficile).

As the most common healthcare-associated infection in U.S. hospitals and other congregate care settings, the Centers for Disease Control and Prevention has classified C. difficile infection as an urgent public health threat.¹ C. difficile infection is extremely contagious, affecting approximately 500,000 people in the U.S. each year,², ³ and resulting in almost 30,000 deaths per year.⁴ 

Moreover, those who successfully complete treatment for C. difficile are not always out of the woods: up to one-third of people are likely to get the infection again⁵ and of those, up to six in 10 are likely to be infected yet again.⁶,, In a single center study, up to 84 percent of all patients with recurrent C. difficile infection were hospitalized within one year, with an average of about two hospitalizations per patient.⁶, Total medical costs for patients with recurrent C. difficile infection ranged from $131,000 to $207,000, with inpatient costs accounting for most of the total costs.¹⁰ 

What’s the cause of all this suffering and cost? A tiny anerobic, gram-positive bacterium discovered in 1935, but only linked to human diarrhea-disease in the 1970s. These hardy bacteria can colonize the colon deep within the large intestine, where they may flourish, especially in the absence of the protective ‘good bacteria’ that live in the gut.²

C. difficile infections can range from mild to severe to deadly. In mild cases, symptoms may include watery diarrhea three or more times a day for more than one day and mild abdominal cramps or tenderness; however moderate to severe symptoms may include frequent (10 to 15 times per day) diarrhea, blood or pus in the stool, severe stomach pain, dehydration, nausea and fever. The most severe cases can be fatal and include rapid heart rate, kidney failure, sepsis, colectomy and heart failure.¹⁰, ¹¹, ¹², ¹³

C. difficile is highly contagious and can spread by direct contact with someone who is infected with or is an asymptomatic carrier of the bacteria, indirect contact when in close proximity with someone with the infection and contact with contaminated surfaces.¹², ¹³ And while anyone can catch C. difficile infection, the risk for infection is higher for people who are taking, or have recently taken, antibiotics, have been hospitalized or spent time in a nursing home or other congregate care facility, have a weakened immune system or are 65 years of age or older.¹²

One of the most challenging aspects of C. difficile infections is the risk of recurrence. The go-to first line treatment for an initial infection is usually a 10-day course of antibiotics.¹⁴ ¹⁵ But even if it appears to work, the infection can reappear anywhere between two and eight weeks after the first infection clears.²,, ¹⁶, ¹⁷ In fact, C. difficile infection returns in about 35 percent of patients within eight weeks of initial infection², ¹⁷ and accounts for an estimated 75,000 to 175,000 additional cases per year.¹⁸, ¹⁹ Moreover, up to 65 percent of those patients go on to experience additional recurrences.¹⁷, ²⁰ 

Paradoxically, one of the primary risk factors for recurrent C. difficile infection is the treatment with antibiotics.¹⁵, ¹⁶, ²¹ While the antibiotics stop the growth of disease-causing bacteria – including C. difficile, they can also wipe out the beneficial species of bacteria. This disrupts the delicate balance of protective microorganisms in the human gut, called the microbiome. When the microbiome is disrupted, a state called dysbiosis, it can create an environment in which C. difficile bacteria can proliferate and potentially cause C. difficile infection.²² In fact, taking antibiotics for an extended period for any infection can cause this disruption, raising the risk for C. difficile infection and a cycle of recurring infections.  

What can be done to combat C. difficile infection? Of course, the best defense against C. difficile infection is prevention,¹⁵, ²³ including frequent hand washing, cleaning and disinfecting surfaces and exercising caution by controlling contact and wearing personal protective equipment when caring for someone with C. difficile. It is important to use soap as alcohol-based hand gels will not kill C. difficile infection. The role of the gut microbiome is increasingly of interest as researchers look to develop potential treatments for recurrent C. difficile infection. This includes promising microbiome-based therapies that may help break the vicious cycle of recurrent C. difficile infection.

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¹ Centers for Disease Control and Prevention website. 2021 Regulatory Oversight and Safety of Probiotic Use. Accessed September 25, 2021.

² Smits WK, Lyras D, Lacy DB, Wilcox MH, Kuiiper EJ. Clostridium difficile infection. Nat Rev Dis Primers. 2016;2:16020.

³ Guh AY, Mu Y, Winston LG, et al. Introduction to the human gut microbiota. N Engl J Med. 2021;382(14):1320-1330.

Lessa FC, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372(9):825-834.

Kao D, et al. Effect of oral capsule- vs colonoscopy- delivered fecal microbiota transplantation on recurrent clostridium difficile infection: A randomized clinical trial. JAMA. 2017;318(20):1985-1993.

⁶ Rodrigues R, Barber GE, Ananthakrishnan AN. A comprehensive study of costs associated with recurrent Clostridioides difficile infection. Infect Control Hosp Epidemiol. 2017;38(2):196-202.

⁷ Unni S, Scott T, Boules M, Teigland, C, Parente A, Nelson W. Healthcare burden and costs of recurrent Clostridioides difficile infection in the Medicare population. Presented at: AMCP 2020; April 21-24, 2020; Houston, TX.

⁸ Lurienne L, Bandinelli P, Galvain T, Coursel CA, Oneto C, Feuerstadt P.  Perception of quality of life in people experiencing or having experienced a Clostridioides difficile infection: a US population survey. J Patient Rep Outcomes. 2020;4(1):14.

⁹ Mayo Clinic website. 2021 C. difficile – Diagnosis and treatment. Accessed September 25, 2021.

¹⁰ Feuerstadt P, Strong L, Dahdal DN, et al. Healthcare resource utilization and direct medical costs associated with index and recurrent Clostridioides difficile infection: a real-world data analysis. J Med Econ. 2020 ;23(6) :603-609.

¹¹ Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015;372(16):1539-1548.

¹² Fernandez-Garcia L, Blasco L, Lopez M, Tomas M. Clostridium difficle infection: pathogenesis, diagnosis and treatment, Clostridium difficile – A Comprehensive Overview, Shymaa Enany, Intech Open, DOI: 10.5772/67754. Available from:

¹³ Bien J, Palagani V, Bozko P. The intestinal microbiota dysbiosis and Clostridium difficile infection: is there a relationship with inflammatory bowel disease? Therap Adv Gastroenterol. 2013;6(1):53-68.

¹⁴ McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48.

¹⁵ Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis. 2021;73(5):e1029-e1044.

¹⁶ Cornely OA, Miller MA, Louie TJ, Crook DW, Gorbach SL. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis. 2012;55(suppl 2):s154-s161.

¹⁷ Kelly CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012;18(suppl 6):21-27.

¹⁸ Burton HE, Mitchell SA, Watt M. A systematic literature review of economic evaluations of antibiotic treatments for Clostridium difficile infection. Pharmacoeconomics. 2017;35(11):1123-1140.

¹⁹ Shields K, Araujo-Castillo RV, Theethira TG, Alonso CD, Kelly CP.Recurrent Clostridioides difficile infection: from colonization to cure. Anaerobe. 2015;34:59-73.

²⁰ Weiss GA, Hennet T. Mechanisms and consequences of intestinal dysbiosis. Cell Mol Life Sci. 2017;74(16):2959-2977.

²¹ Langdon A, Crook N, Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med. 2016;8(1):39.

²² Bien J, et al. Therap Adv Gastroenterol. 2013;6(1):53-68. 2. Staley C, et al. Arch Med Res. 2017;48(8):766-773.

²³ Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infection. Am J Gastroenterol. 2013;108(4):478-498.

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