1. Basic Facts About Clostridium difficile and Clostridium difficile infection (CDI)
Clostridium difficile (C. difficile) is an anaerobic, gram-positive bacterium. It can exist in two forms: a dormant spore that has a tough protein coat, and a vegetative form that results from spore germination. Because of the anaerobic nature of the bacteria, the dormant spore is the infectious and transmissible form.1 C. difficile was first detected in the lower intestinal tract of newborns in 1935, but it is not considered to be a normal commensal bacterium of the gut.2 It was not until 1978 that it was understood to cause the disease commonly known as Clostridium difficile infection (CDI). C. difficile is a common bacteria and has been isolated from soil, houses, shops and healthcare facilities.3, 4
How Is CDI Caused?
C. difficile causes pseudomembranous colitis, a severe inflammatory infection of the colon that is commonly known as CDI. In general, two conditions — colonization with C. difficile and exposure to antibiotics — are necessary prerequisites for infection to develop. In healthy individuals, C. difficile spores may colonize the gut, coexisting with a diverse range of bacteria — known as commensals — that make up the microbiota. The diverse commensal bacteria form a mucus layer on the epithelial cells of the intestinal tract.
However, following antibiotic treatment, the normal gut microbiota is disrupted and many commensal bacteria are killed. In this situation, microorganisms such as C. difficile may not be affected by the antibiotic and can proliferate. As a result, C. difficile spores can attach to the epithelial wall of the small intestine, germinate into the vegetative state, and reproduce. This causes the release of two exotoxins — toxin A and toxin B — which attack the epithelial cells and cause mucosal damage.5 Studies suggest that toxin B is responsible for C. difficile virulence.6, 7
The susceptibility of the patient or the virulence of the C. difficile strain may also play a role in determining whether the infection develops. Some people who experience colonization and exposure to antibiotics may become only asymptomatically colonized.8
While most antibiotics are suspected of being a trigger for the development of CDI, the risk appears to be higher for specific classes of antibiotics such as cephalosporins, fluoroquinolones and clindamycin. In recent outbreaks, the fluoroquinolone class of antibiotics has been implicated.9, 10
Who Is Affected by CDI?
CDI can affect people of all ages. However, the risk of developing CDI is greatest in patients over 65, those with chronic health conditions and comorbidities such as diabetes, those undergoing gastrointestinal surgery, those who are immunocompromised and those who have a history of prior antibiotic use.11 Additionally, those who are subject to long stays in healthcare settings such as hospitals, nursing homes and long-term care facilities are also at increased risk.
Depending on the virulence of the infecting C. difficile strain, the toxins can cause illness ranging from mild diarrhea to pseudomembranous colitis. In all cases, the major symptom of CDI is diarrhea. Mild cases may experience only this symptom, while severe cases can include severe abdominal cramping, blood or pus in the stool, nausea, a swollen abdomen, kidney failure and an increased white blood cell count.12 A significant proportion of patients require a colectomy — removal of the colon. Severe infection can lead to sepsis and death.
How Is CDI Treated?
CDI is treated by the administration of antibiotics that can kill C. difficile bacteria. For milder cases of CDI, metronidazole is the most commonly prescribed antibiotic. For more severe cases, vancomycin or fidaxomicin administered orally will most likely be prescribed. A course of treatment usually lasts for a minimum of 10 days. More recently, fecal transplants — transplants of stool from healthy people — have been used to treat CDI with some success, although the long-term safety has not been established.12
What Is Recurrent CDI?
For a significant proportion of CDI patients, recurrent disease remains a risk. Recurrent disease occurs in around 20% of patients, can occur as little as one to two weeks after resolution of the initial infection, and may occur multiple times. The first recurrence is usually treated with the same antibiotics that were used to treat the initial infection. Multiple recurrent infections are usually treated with vancomycin or fidaxomicin.13