At least 70% of individuals who ingest the Clostridium difficile spores remain asymptomatic but about 1/3rd of patients do become ill. Symptoms may develop as early as the first day after antibiotic exposure to more than 6 to 8 weeks after completion of antibiotic therapy.
The symptoms of include the following:
Blood work may show leukocytosis and worsening of kidney function. These two parameters indicate a severe infection and these patients should be treated with oral vancomycin rather than metronidazole. Severe cases may also present with hypokalemia and hypoalbuminemia, elevated BUN and creatinine. Tests for Clostridium difficile and toxin on stool should be done in symptomatic patients only. Asymptomatic patients do not need stool testing. The stools may be positive for blood and leukocytes. Stool culture is most sensitive test but the results are not available immediately. Tests for toxins can be done via ELISA and PCR and repeated testing may be required.
Endoscopy is not routinely done in presence of CDI. It may show the pseudomembranes in patients with severe disease. However, there is a high risk of bowel perforation in acute cases. Computed tomography scanning of the abdomen is performed when the cause of colitis is unknown or another cause is suspected. It may show thickening of colonic wall, ascites, irregular bowel wall and stranding of fat. Plain X-ray is ideal to look for toxic megacolon.
Basic treatment includes the following:
Medical treatment then depends on the severity of the colitis. For mild to moderate colitis, metronidazole is the treatment of choice and administered orally for 10 to 14 days. Severe colitis may require vancomycin four times a day for 10 to 14 days. Fidaxomicin is a newer drug which is as effective as vancomycin with lower rates of recurrence. The cost of fidaxomicin is the limiting factor. A ten day course is close to $3,000.
Fecal transplants are also recommended for chronic relapsing cases. These transplants are about 90% effective. Fecal transplant is performed by transferring stools of a healthy donor into a patient with recurrent CDI to replenish the normal bacterial flora. Fecal transplants are done in three ways, retention enema, colonoscopy and nasogastric tube. Long term data following fecal transplantation reveal that relapse rates are low. There are some studies which show that fecal transplants may be more effective than antibiotics in recurrent cases of CDI. However it should be noted that fecal transplants can transmit infections like HIV, hepatitis and other retroviruses. So the donor must be carefully selected and screened for infectious diseases .
The use of probiotics is heavily promoted for treatment of Clostridium difficile colitis. Probiotics contain live nonpathogenic organisms. Unfortunately there is no consensus on the efficiency of probiotics. Even when they do work, less than 60% of patients benefit from probiotics. Some evidence suggests that certain probiotic strains, such as certain Lactobacillus species, and Saccharomyces boulardii, are effective in preventing CDI, but the evidence is inconclusive. It appears that finding the right combination of probiotics instead of a single organism will be necessary to prevent and treat CDI. Probiotics may be used as a preventive measure but there is no evidence that they are effective in acute cases of CDI.
Patient with fulminant colitis and toxic megacolon may require emergent surgery. The colon may have to be resected and a colostomy is performed. The decision to operate requires experience as these individuals are critically ill and have a high mortality rate. In general, these patients have elevated levels of lactate, leukocytosis and acute renal failure.
Relapse rates of 15 to 30% have been reported after treatment for CDI. The relapse may occur anywhere from 3 days to 3 weeks after treatment is stopped. Reasons for relapse include continued antibiotic exposure, reinfection from the environment and failure to eradicate the organism from the gastrointestinal tract. Management of the first relapse is the same as the initial episode, but the severity of the relapse needs to be clarified. For mild cases of relapse, metronidazole can be used but for severe and subsequent recurrence long term therapy with metronidazole may result in adverse drug effects. Vancomycin is recommended for later recurrences using a pulse or a tapered regimen.
The majority of patients with pseudomembranous colitis do recover without adverse sequalae. Most patients require hydration for a few days. Patients with severe colitis may have adverse outcomes depending on their response to treatment. For those who fail medical therapy and require surgery, the prognosis is guarded. Some of these patients may require a permanent colostomy and may develop multiple organ failure.
The majority of pseudomembranous colitis cases are associated with some type of prior healthcare related exposure. Antibiotic use is the most important risk factor. Antibiotics disrupt the normal protective bacterial flora in the gastrointestinal tract. Even a short term exposure to antibiotics can increase the patients risk which increases with the duration of antibiotic usage. The risk remains high after two months of usage even after discontinuation.
Outpatient visits to healthcare workers have been linked to the disorder. Since outpatient clinics may not always be regularly disinfected, the environment is easily contaminated with Clostridium difficile spores. Many patients who are infected or colonized, followup up with their primary physicians after discharge and some of these patients continue to shed spores even after completing treatment of Clostridium difficile. The heaviest spore contamination is often found in bathrooms, surfaces, tables and chairs touched by the patient. More important healthcare workers can also transport the spores on their hands and clothes to hospitals and into their homes.
Contact with colonized patients is also a risk factor for community acquired CDI, it is estimated that anywhere from 20 - 50% of asymptomatic patients in hospitals and long term healthcare facilities are colonized with Clostridium difficile. In addition, toddlers and infants can also be asymptomatic carriers. Thus coming into contact with feces or other objects can lead to transmission of spores.
Long term use of proton pump inhibitors (PPIs) is also associated with a high risk of CDI. Almost all PPIs studies have been shown to have a high risk for acquiring CDI. The increase availability of PP over the counter is of public concern .
Risk factors with questionable evidence
Even though Clostridium difficile has been found in meat and some vegetable there role of food in transmission of spores is questionable. It should be noted that the spores of Clostridium difficile can survive temperature used to cook and store frozen foods.
Even though Clostridium difficile is found in healthy dogs and cats, there is no solid evidence that direct transmission of this pathogen can occur from animals to humans.
Antidepressant medications like mirtazapine (Remeron) and fluoxetine (Prozac) have been linked to a high risk of CDI. However, the relationship is not direct and it is not known if there are other factors linked.
Use of alcohol-based hand sanitizers is widespread in hospitals and it is believed that Clostridium difficile spores have built up resistance to this disinfectant. In addition, there is a belief that spores may be more likely to be transferred in healthcare workers who use this sanitizers. Unfortunately no study has shown that this occurs.
Clostridium difficile infection has changed over the past decade in terms of its epidemiology. There are more reported cases of the infection, the severity of the illness has increased and there are more treatment failures than in the past. Deaths and hospitalizations related to CDI have increased significantly over the past 2 decades. The majority of CDI outbreaks have their onset outside hospitals and most start in nursing home patients or in outpatient settings.
Unlike the past, populations that traditionally have been considered to be at low risk, like young healthy adults and children are also developing CDI and many affected individuals lack the predisposing factors such as advanced age, antibiotic exposure or a recent hospital stay. Healthcare workers must be aware of the change in demographics of the patient population now at risk for CDI.
In the USA there are about 3 million cases of CDI every year. Of these at least 14,000 people die from the infection. Over the past 2 decades, the rates of CDI have dramatically increased. This is a common observation not only in the USA but globally. Overall CDI is more common in elderly people  .
Regardless of whether the infection develops in the community or hospital, CDI is transmitted by via oral fecal contact from an infected individual to non-infected sources through ingestion of spores. The Clostridium difficile spores are durable outside the human body and persist for months. People who come into contact with them can easily ingest them. Initially the spores are not infectious until they are ingested and germinate. The ingested spore may remain dormant in the gastrointestinal tract until prolonged use of antibiotics may decrease the normal bacterial flora and this allows for the Clostridium difficile to overgrow rapidly.
The symptoms of the condition are produced by two major toxins – toxin A and toxin B. These protein molecules cause inflammation and damage to the mucosal lining of the colon. Toxin B is chiefly responsible for the colon injury and the virulence. Recently a third toxin (BI/NAP1/027) was discovered and it is associated with the most severe colitis, highest rate of recurrence and mortality. The NAP1 strain is known to produce many spores which are much more toxic than the other strains. In addition, the extra spores also result in a higher risk of transmission. The proliferation of the NAP1 strain has been associated with widespread use of the 4th generation fluoroquinolone antibiotics like moxifloxacin and gatifloxacin, but virtually all antibiotics have been shown to provoke Clostridium difficile overgrowth in the colon.
Preventing CDI is not easy. Isolating infected patients is not always possible in nursing homes. However, once a patient has been diagnosed with CDI, the following recommendations apply:
Clostridium difficile is a gram positive spore-forming anaerobic organism that is known to cause antibiotic-associated diarrhea and colitis. Clostridium difficile infection (CDI) can present with mild to severe non-bloody diarrhea with abdominal cramps. While once Clostridium difficile colitis was strictly a nosocomial infection, this is no longer true. An increasing number of cases have now been recognized in the community and it appears that several strains of Clostridium difficile exist with varying degrees of potency. In the past CDI was once only a hospital acquired infection but recent studies indicate that today anywhere from 20-45 percent of cases are community acquired. In fact at least 5% of patients with CDI have no history of recent health setting exposure.
The symptoms of the disorder may occur anywhere from 2-21 days after the antibiotic was discontinued. On sigmoidoscopy one may visualize pseudomembranes attached to the intestinal mucosa. In rare cases, CDI can present with abdominal distention, pain and life threatening colitis (toxic colitis)    .
Currently CDI cases are categorized as follows:
Pseudomembranous colitis is a medical disorder of antibiotic-associated diarrhea, usually caused by Clostridium difficile. The use of antibiotics is the number one risk factor for the development of the condition. One may develop profuse watery diarrhea and abdominal cramps. In some cases, discontinuation of the antibiotics helps resolve the condition. In other cases, the patient may need to take specific antibiotics for 10 to 14 days to kill the harmful bacteria. In rare cases, some patients may require surgery to remove the diseased colon. People who develop the disorder can easily transmit the infection to others and thus, hand washing regularly is recommended. At home, it is important to wipe all inanimate objects with a sanitizer and offer the individual a personal commode. The majority of patients who are treated promptly do recover within 2 to 4 days. Unfortunately, relapses can occur and require more specific antibiotic treatment.