What are the other Names for this Condition? (Also known as/Synonyms)

• C. Difficile Colitis
• CDAD (Clostridium Difficile Associated Diarrhea)
• Clostridium Difficile Colitis

What is Clostridium Difficile Associated Diarrhea? (Definition/Background Information)

• Clostridium Difficile Associated Diarrhea (CDAD) is a hospital-acquired infection caused by the bacterium Clostridium difficile. Often, patients also have an associated recent antibiotic use
• CDAD should be distinguished from diarrhea that is caused as a ‘sensitivity reaction’ to antibiotics. Diarrhea caused due to a side-effect of antibiotic therapy, is called antibiotic-associated diarrhea.  Antibiotic-associated diarrhea is not the same as C. Difficile Associated Diarrhea
• Individuals with CDAD are often not known to have sensitivity to antibiotics and have signs of the infection, such as fever accompanying the diarrhea. Inflammation of the colon is observed in endoscopy and affected individuals have positive stool test results for C. difficile toxins (toxin A and/or toxin B)
• C. difficile spores remain viable for months-to-years outside the body, in the environment, making the infection chances high in individuals, who have been admitted to hospitals
• Complications of CDAD include recurrence of diarrhea, dehydration, toxic megacolon, peritonitis, and sepsis
• CDAD is treated by stopping the antibiotic therapy, which resulted in the infection and starting a different set of antibiotics that would kill the disease- causing Clostridium difficile bacteria. It has been noted that ceasing current antibiotic treatment cures CDAD in some individuals, without the need for further antibiotic therapy

Who gets Clostridium Difficile Associated Diarrhea? (Age and Sex Distribution)

• Individuals, who are undergoing antimicrobial therapy, may get Clostridium Difficile Associated Diarrhea. The infection may also occur within 8 weeks of stopping therapy
• CDAD is more common among middle-aged and older adults
• Both males and females can be affected
• No racial or ethnic predilection is noted

What are the Risk Factors for Clostridium Difficile Associated Diarrhea? (Predisposing Factors)

The following may be the risk factors for Clostridium Difficile Associated Diarrhea:

• Undergoing antibiotic treatment or anti-microbial therapy increases the risk of CDAD. The most common antibiotics associated with C. difficile include clindamycin, cephalosporins, ampicillin, amoxicillin, erythromycin, and fluoroquinolones
• Undergoing gastrointestinal (GI) surgery, such as partial or complete removal of the colon (partial or complete colectomy)
• Environments at hospitals, nursing homes and other health care settings with C. difficile spores

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Clostridium Difficile Associated Diarrhea? (Etiology)

• Clostridium Difficile Associated Diarrhea is caused by the bacterium called Clostridium difficile
• It is an anaerobic, gram positive, spore-forming rod type bacterium. C. difficile produces two toxins, called ‘Toxin A’ and ‘Toxin B’
• This bacteria forms spores that remain viable (alive) for many months to years, in a hospital environment

Normally, there are many different types of bacteria that live in the colon that do not cause disease in humans.  These friendly bacteria, under normal circumstances, prevent the growth and colonization of disease causing C. difficile bacteria.

When an antibiotic therapy is given, normal bacteria in the colon are killed. Hence, when the friendly bacteria are killed by antibacterial therapy, it creates an environment in the colon, where disease-causing C. difficile bacteria can grow. When these bacteria grow in large numbers, they result in C. Difficile Associated Diarrhea infection.

What are the Signs and Symptoms of Clostridium Difficile Associated Diarrhea?

Signs and symptoms associated with Clostridium Difficile Associated Diarrhea include:

• C. Difficile Diarrhea is defined as an individual having diarrhea in the following manner:
  • 6 watery stools in 36 hours
  • 3 unformed stools in 24 hours for 2 days
  • 8 unformed stools over 2 days (48 hours)
• Fever
• Inflammation of colon causing abdominal pain
• Increase in white blood cell count (leukocytosis)

How is Clostridium Difficile Associated Diarrhea Diagnosed?

When an individual displays the signs and symptoms of C. Difficile Associated Diarrhea, the physician performs the following tests to diagnose the condition:

• Complete physical examination and thorough medical history. The medical history includes an evaluation of the use of current antibiotics or a recent antibiotic treatment
• Enzyme immunoassays (EIA), which have a 75-90% sensitivity and high specificity. There are two different immune assays, one for ‘Toxin A’ and another for ‘Toxin B’
  • Sensitivity refers to ‘true positive’ or in other words, diagnosis of a person with the disease, as having the disease
  • Specificity or ‘true negative’ refers to diagnosis of a person without the disease, as disease-free
• Anaerobic cell culture of stools: Stool cultures are helpful in determining, whether an individual has C-difficile bacteria within the colon. However, since not all individuals with C-difficile bacteria in the colon have signs and symptoms, this antibiotic culture does not differentiate between C-difficile organisms that cause toxins and those that do not cause toxin production. The anaerobic culture of stools for C-difficile is usually reserved for an epidemiological study of the presence of organism in a community
• Polymerase chain reaction (PCR): In this test, the DNA is sequenced to check for the presence of toxin-producing genes in C. difficile. A PCR test is not usually used for diagnostic purposes, but instead is performed to study the types of C. difficile bacteria that exist in a community (for epidemiological purposes)
• Cell culture cytotoxin test: It detects the presence of toxins in a fecal sample (20-25% of strains are non-toxigenic).  A lab cell line is grown in the presence of fecal sample on two dishes. One dish has an antitoxin and the second dish does not have antitoxin in it. If C. difficile toxins are present, the cells on the dish without the antitoxin die; the cells grow in a monolayer on the dish with the antitoxin. In the absence of C. difficile toxins, cells are alive on both dishes
• Colonoscopy: A colonoscopy would show inflammation of the colon with formation of pseudomembranes, when examined by a gastroenterologist

CDAD should not be confused with antibiotic-associated diarrhea. An antibiotic-associated diarrhea is caused, due to an individual’s reaction to an antibiotic therapy. The individuals usually do not have fever.

• Usually, such individuals have a previous history of reaction to antibiotics
• When a colonoscopy is performed, the colon appears normal on the colonoscopic examination
• An antibiotic-associated diarrhea recovers without any complications
• The usual treatment for this condition is a stoppage of the antibiotic medications, upon which the diarrhea stops

On the other hand, a Clostridium Difficile-Associated Diarrhea occurs with no prior history of antibiotic sensitivity. The diarrhea is associated with fever. Many complications can occur, including recurrences and relapses. A withdrawal of the antibiotics may occasionally help, but the diarrhea may continue after the stoppage of the antibiotic.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Clostridium Difficile Associated Diarrhea?

The complications associated with C. Difficile Associated Diarrhea include:

• Recurrence: Once an individual has CDAD, the relapse (or recurrence) rate is 30%. Usually, the relapse occurs 1-3 weeks after completion of the treatment. The relapse of CDAD occurs, due to persistence of the same strain of C-difficile spores within an individual. The re-infection is defined as a situation, where an individual gets infected with a new strain of C-difficile that causes an infection. Prolonged management with antibiotics or polymers that bind the toxin, might be necessary
• Toxic megacolon: The collection of stool and gases causes the colon to enlarge and this can lead to rupture of the colon. Toxic megacolon shows dilated bowels on an abdominal x-ray
• Colonic perforation or peritonitis: Enlargement of the colon leads to rupture of the membrane. This causes a release of bacteria into the abdominal cavity, leading to severe infection
• Sepsis: The release of bacteria and toxins into blood, can lead to multi-organ failure

How is Clostridium Difficile Associated Diarrhea Treated?

Clostridium Difficile-Associated Diarrhea is treated in the following manner:

• Cease current anti-microbial treatment, that which is the possible cause of CDAD
• Avoid anti-motility agents (drugs used to stop diarrhea symptoms)
• Infection control: Maintaining sterile conditions to prevent spread of infection, while also preventing re-infection
• Supportive measures: Provision of fluids to maintain normal fluid balance
• Antibiotic treatment:
  • Metranidazole is administered intravenously or via oral administration
  • Vancomycin may be given orally or topically
  • Combination of metronidazole and vancomycin may be administered
  • Vancomycin enema or surgery may be recommended in cases of severe infection
• Polymer treatment: Tolevamer is a polymer to which toxins A and B bind, thus neutralizing fluid collection in the colon (this is now under Phase II clinical trial)
• Stool transplantation is an experimental treatment for C. difficile infections. The stool transplant is usually performed by injecting a stool preparation from a different individual, into the rectum. The idea behind a stool transplant is to increase the number of normal bacteria that are found in the colon. Increasing the number of normal bacteria in the colon would help stop the growth of disease-causing Clostridium difficile bacteria within the colon

How can Clostridium Difficile Associated Diarrhea be Prevented?

Clostridium Difficile-Associated Diarrhea can be prevented by adopting the following measures:

• When admitted to the hospital, if possible, avoid sharing a room or bathroom with other patients
• Healthcare settings should maintain a clean and hygienic environment
• All healthcare providers should wash their hands frequently and use gloves, while handling body fluids
• By adopting a careful use of antimicrobial products
• Use of disposable thermometers

What is the Prognosis of Clostridium Difficile Associated Diarrhea? (Outcomes/Resolutions)

The prognosis of C. Difficile Associated Diarrhea is as follows:

• Prognosis depends on the severity of infection. Individuals with severe infections have worse prognosis, than individuals with mild infection
• Individuals, who respond completely to treatment have excellent prognosis, compared to individuals, who have a relapse or recurrence of the infection
• Certain mutant strains of C. difficile show a 20-fold increase in toxin production and individuals have poorer prognoses, due to a poor response to metronidazole. In such cases, the mortality rates are higher, in individuals over 75 years of age
• The outcome is worse, if the infection is complicated by toxic megacolon, peritonitis, or sepsis

Additional and Relevant Useful Information for Clostridium Difficile Associated Diarrhea:

• A hospital-acquired infection is called a “nosocomial infection”
• An antibiotic-associated diarrhea is different from a C. Difficile Associated Diarrhea
• Not all diarrheas that occur in the hospital are caused by the bacterium C. difficile
• An individual may have C. difficile in their body, but may not show any signs and symptoms. Such individuals are carriers of the infection
• Newborns have been known to have Clostridium difficile in their stools, but rarely show any infection signs