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Clostridioides Difficile Infection (CDI)

Clostridioides difficile infection or C. difficile is a bacterium that can infect the large bowel (or colon) and is a major cause of infectious colitis and diarrhea in healthcare settings around the world. Infectious colitis is redness, swelling, and inflammation of the colon. (It was formerly known as Clostridium difficile; however, was renamed after it was reclassified in 2016.)

What is it?

The C. difficile infection occurs when the C. difficile bacteria multiply and are able to grow within the gastrointestinal (GI) system. The bacteria and its spores resist heat, acid, and antibiotics. For most people infected by CDI, symptoms will begin in 2-3 days. In some cases, CDI may take more than one week and up to 28 days to become noticeable. CDI secretes several toxins, or poisonous substances in the colon (large intestine). These toxins cause inflammation in the GI tract and diarrhea.

Under normal circumstances, the intestinal tract contains millions of bacteria, referred to as “normal gut flora” or “normal microbiota.” These bacteria have many different functions, and one of them is to protect us against foreign infections. This immune function of the microbiota is sometimes called “colonization resistance”. Our normal gut microbiota can be undermined and weakened when we take antibiotics. The changes that result from antibiotics can allow C. difficile to multiply and release toxins causing colitis by damaging the lining of the colon. This can result in diarrhea, abdominal pain, fever, and even sepsis. 

But the mere exposure to C. Difficile doesn’t necessarily mean that one will develop C.difficile colitis. In fact, a person can have the bacteria inside themselves and have no symptoms. This is referred to as being ‘colonized’ by the bacteria.

How common is CDI?

According to the Centers for Disease Control and Prevention (CDC), almost half a million of cases of CDI occurred in 2011 in the United States. In the last 10 years its prevalence has decreased but it still affects over 350,000 patients a year. It is the most common hospital-acquired infection in the U.S. A decade ago, the vast majority of people who became infected with C.Difficile had some recent exposure to a hospital or other healthcare facility. With better infection control and other measures, the risk of acquiring CDI following a hospital admission or healthcare facility exposure has decreased. Community-acquired infections, in patients who have not been hospitalized, have remained stable, affecting over 150,000 people a year according to CDC estimates. The burden of this infection remains a major problem for our healthcare system.

CDI has significant effects on our healthcare related costs in the United States. Since CDI prolongs hospital stays by 2.8 to 10.4 days, it raises the cost of a hospitalization by over $42,000 per admission. Healthcare-related costs associated with CDI range from $1.9 to 7 billion USD each year.

How does Clostridioides Difficile Infections Spread?

C.difficile is widely present in the environment and can be found on surfaces like doorknobs, bedside tables, and counters, especially in healthcare facilities. It can spread through contaminated objects and/or the hands of healthcare workers. Transmission occurs through what is called the “fecal-oral” route. This means that the C.Difficile bacteria that come from the bowel movement of an infected individual are ingested by another individual, who subsequently gets the infection.

Thorough hand washing with soap and water is important as hand sanitizers cannot kill CDI.

Types of Clostridioides Difficile Infections

  • Non-Severe CDI– The most common form of CDI seen is either mild colitis, or simple diarrhea. This diarrhea is watery and contains mucus, but generally not blood. A sigmoidoscopy usually shows normal tissue in the colon. This test involves placing an endoscope through the anus and into the last part of the colon. An endoscope is a long flexible tube with a camera and light on the end. The camera allows your healthcare provider to see inside your GI tract during the test.
  • Severe CDI– Severe colitis is often present with a case of severe CDI or full-blown C. difficile-associated colitis. Severe CDI occurs when the patient has very bad diarrhea and possible dehydration, as well as abnormal lab tests and/or X-rays.  
  • Fulminant CDI– This is the worst type of CDI and is often seen with very serious complications. This can be life-threatening and occurs in 3% of patients. Most of those affected by this type are elderly and/or debilitated from other diseases. Patients with this level feel severe lower abdominal pain, diarrhea, high fever with chills, and rapid heartbeat. They usually have markedly abnormal blood tests and can have low blood pressure. 

What are the risk factors associated with CDI?

The main risk factor for CDI is exposure to the bacteria and use of antibiotics. Exposure most often occurs in a hospital setting. Long-term antibiotic treatments or taking multiple antibiotics at the same time can further increase the risk for CDI. 

There are also certain patient characteristics that can increase the risk, including

  • advanced age (over 65 years old),
  • having inflammatory bowel disease (IBD),
  • liver cirrhosis,
  • chronic kidney disease,
  • being a transplant recipient
  • or any illness where the immune system is compromised.

How is CDI Treated?

The primary treatment for C. difficile is an antibiotic that kills the bacteria itself. The choice of antibiotics depends on the severity and recurrence status of the infection. Supportive care, and close monitoring in a hospital setting is necessary for severe cases.

In some cases of recurrent Clostridioides Difficile Infection, Fecal Microbiota Transplant (FMT) may be recommended. With FMT, stool from a healthy donor is placed in the patient in an effort to add more of the ‘good’ bacteria. This can be highly effective in difficult cases. Surgery may be needed in a small subset of patients with toxic megacolon, colonic perforation, or necrotizing colitis.

Diagnosis in Adults

Generally, testing for CDI should be done in any patient who has new unexplained diarrhea. This is defined as three or more unformed bowel movements a day without the use of laxatives. Currently there are many laboratory testing options for detecting C. difficile. These tests usually check for toxin or genes from the bacteria, rather than culturing the bacteria itself.  The name ‘difficile’ was used because the bacteria is quite difficult to culture. Despite multiple tests for this bacterium, each has limitations, so consult your medical professional if you think that you need to be tested for this infection.

Diagnosis in Children

For children, diagnostic testing recommendations are based on age.

  • Children younger than 12 months of age should not be tested. C. diff can be a normal finding in newborns and not cause illness.
  • Children older than 12 months may be tested if they have prolonged diarrhea, have risk factors (such as IBD, cystic fibrosis, malignancy) and other causes of diarrhea have been ruled out.
  • Children older than 3 years have the same diagnostic recommendations as adults. Other possible causes of diarrhea should be investigated at the same time. This includes viral infections or other conditions.

Treatment of CDI

As with any type of acute diarrhea, maintaining hydration and adequate nutrition is important. If the patient is taking antibiotics that may have contributed to the development of CDI, those should be stopped if possible.

The primary treatment for C. difficile is an antibiotic such as Fidaxomicin™ or Vancomycin™ that kills the bacteria itself. Sometimes, if symptoms are severe, antibiotics can be used even before the diagnosis is confirmed. Supportive care, and close monitoring in a hospital setting are necessary for severe or fulminant cases.

In cases of recurrence of CDI, patients are treated with another course of antibiotics. Depending on the risk for further recurrence, there are other measures one can take to decrease that risk, including an intravenous infusion of monoclonal antibody called bezlotoxumab. 

In some cases of recurrent disease, Fecal Microbiota Transplant (FMT) may be recommended.  With FMT, stool from a healthy donor is placed in the patient in an effort to add more ‘good’ bacteria to re-strengthen the “colonization resistance.”

Rarely, surgery may be needed when the most severe complication of fulminant disease is present. This complication is termed “toxic megacolon” and can result in colonic perforation (a hole or tear in the lining of the colon) or necrotizing colitis (an inflammation in the intestines (usually the colon) that can be life-threatening if not treated right away). Thankfully, advances in research have made this complication exceedingly rare. 

How Likely am I to get CDI more than once?

CDI recurrence is the reappearance of diarrhea and other CDI symptoms after treatment ends following an initial improvement or response to the antibiotic used to treat the infection.

In other words, the patient responds to the antibiotics and feels better, but after antibiotics are stopped, the symptoms and the infection come back. This most commonly happens within 4-8 weeks of completion of therapy.

It is estimated that approximately 25% of patients with CDI who receive a standard of care antibiotic therapy will have at least one recurrence. After each subsequent recurrence, a future recurrence becomes more likely. For example, after a first recurrence, the risk of a second recurrence is about 40%. Recurrences occur because the antibiotics that we use to treat CDI aren’t effective against the C. Difficile spore (the more resilient form of this bacterium that results in recurrence and transmission from person to person).

Prevention

The bacteria spreads for as long as the patient’s diarrhea persists. Prevention strategies should be used in every suspected case, not only in confirmed patients. In the hospital and other health care facilities, measures include proper use of personal protective equipment (PPE): Gloves and disposable gowns should be used by anyone in contact with the patient during the duration of symptoms. Proper hand washing by the patient and anyone in contact with them. (Note: alcohol-based hand sanitizer does not kill C. difficile well, but soap and warm water work very well on our hands).

More Information

Learn more about other bacteria that can affect the gastrointestinal tract.

Page updated July 2023

Adapted from IFFGD’s Publication Clostridioides Difficile Factsheet #167  by: Alejandro Llanos-Chea, MD Assistant Professor of Pediatrics, University of Miami Miller School of Medicine; Edited by: Neil Stollman MD, FACP, AGAF, FACG; Alta Bates Summit Medical Center; Adapted from a Fact Sheet by: Charalabos Pothoulakis, M.D., Director, UCLA IBD Center, Division of Digestive Diseases; Associate Director, UCLA CURE: Digestive Diseases Research Center; Professor, David Geffen School of Medicine, University of California
This Fact Sheet is being provided in part by bioMérieux and Seres Therapeutics and donors of IFFGD.

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