Clostridium difficile (C. diff) is an opportunistic pathogen that causes damage to the cells of the intestinal tract. The C. diff pathogen seizes its opportunity when a person’s own natural flora in the gut is diminished. This decrease in natural flora can be caused by various situations, but is usually a result of treatment with antibiotics. C. diff is naturally resistant to many antibiotics making the infection difficult to treat. C. diff is difficult to control and contain, it spreads easily and lives on surfaces for extended periods of time. For this reason it has become one of the top healthcare associated infections in the United States and around the world. The CDC reported just over half a million cases last year, resulting in 15,000 deaths.

Pathophysiology

The pathogen, clostridium difficile, is a gram-positive anaerobic bacterium that produce spores. These spores produce an exotoxin that binds with receptor sites of the epithelial cells of the intestines. The exotoxin binding to the cells is what leads to the inflammation, which later causes diarrhea.

Epidemiology and History

In the late 1960s and early 1970s, antibiotic use became widespread. Antibiotics were over prescribed and soon after this increase in usage, antibiotic associated diarrhea was recognized as a problem. Clindamycin-resisitant bacteria were initially thought to be the only culprit, but strains resistant to penicillins and cephalosporins followed quickly. Around 1990 a new strain, highly-resistant to Clindamycin emerged, and four different hospitals in the United States experienced large outbreaks of diarrhea caused by bacterial infection. Treatment with clindamycin was determined to be a risk factor for this strain, as the resistant bacteria flourished in the now-diminished gut flora.

In 2003 C.diff was found to be more frequent and more severe than ever. It was also becoming more resistant to conventional therapies with a higher recurrence than previously thought. A new strain also emerged during this time that was harder to kill than any before. This new strain produced an increased amount of toxins and it correlated to the increased use of fluoroquinolone as a countermeasure.

One study out of Quebec, Canada looked back on their cases from 1991 to 2001 and found the incidence of hospital acquired C. diff was four times greater than before, while in patients over 65 years old it was ten times what it had been. The current decade has also seen an increase in C. diff rates due to the emergence of new resistant strains.

Transmission

C.diff is spread through fecal-oral route. The spores produced by the bacterium are very hardy and can live on surfaces for extended periods of time. The spores are easily spread by touching a contaminated surface then touching food while eating or preparing. C.diff spores cannot be killed with alcohol based sanitizers; they can only be killed by washing your hands with soap and hot water or wiping surfaces with bleach.

Risk Factors

The toxins from the C. diff spores may or may not cause an infection. In a healthy person, the immune system and normal flora of the intestinal tract will generally kill the spores before they can produce toxins and cause infection. The chance of a person becoming infected is greatly increased if they have been on antibiotics, as this inhibits the growth of the natural flora in the gut that would otherwise kill the invading spores.  Long-term intravenous antibiotics put the person at especially high risk.

If the person is immunocompromised, elderly, or has recently been hospitalized, the chances of contracting C. diff are greatly increased. C. diff can flourish in hospitals, as improperly-cleaned surfaces can retain infectious spores for a long period of time. Having multiple comorbidities puts a person at additional risk and an increased chance of recurrence.

Signs and Symptoms

There is a large range of possible symptoms that may occur with C. diff infection. The most common is diffuse, watery stools (diarrhea). Some people may be asymptomatic but become a carrier of the pathogen. Others may suffer fulminant disease, experience toxic megacolon and require surgery. Some other symptoms may include:

• more than 3 loose stools in 24 hours

• lower abdominal pain and cramping

• fever (in approximately 15% of cases)

• nausea

• anorexia

• leukocytosis

• mucous or occult blood in stool

• elevated creatinine

• elevated lactate

Symptoms can occur anytime during antibiotic therapy and up to 14 days following the completion of antibiotics. There have been cases, however rare, where symptoms began 10 weeks following completion of antibiotics. This may indicate a resurgence of C. diff within the patient’s gut.

Asymptomatic Carriers

About 20% of hospitalized adults and up to 50% of long-term care residents carry the C. diff pathogen and shed the spores in their stool but do not have symptoms. Because they don’t have diarrhea or other symptoms, there is no reason to test, no reason to treat, and no reason for precautions or contact isolation. The medical staff remains unaware while it is transferred from room to room on their hands, scrubs, and shoes. It is essential that healthcare providers follow proper hygiene  protocol even if a patient is not suspected of having a C. diff infection, as asymptomatic carriers are common..

Complications

Protein-losing enteropathy with hypoalbuminemia is one complication known to occur with the C. diff infection. Inflammation of the bowel allows albumin to leak out through the intestinal wall causing colonic loss of albumin. Hepatic synthesis is unable to compensate for the sudden loss resulting in ascites and peripheral edema for the patient. By replacing the albumin and treating the infection this complication is reversible.

Extracolonic involvement is another possible complication. There have been reported cases of C. diff causing appendicitis affecting the small bowel, some soft tissue infections, bacteremia  and reactive arthritis.

Diagnosis

Diagnosis is confirmed by a positive laboratory stool test for C. diff toxins or toxin gene. Patients suspected of having C. diff should provide a liquid stool, and the sample should be sent for C.diff testing not laboratory testing. Laboratory testing does not distinguish between C.diff associated diarrhea and asymptomatic carriage, which does not warrant treatment.

There are different types of testing used by laboratories, some more accurate than others. The most important thing to remember for medical staff is that C.diff toxins break down at room temperature. The stool sample must be delivered to the lab within two hours of collection if the test being used is one based on spore detection.  The lab will be able to store the sample at the correct temperature until the test can be run.

Treatment

When a patient contracts C. diff, they usually are already taking antibiotics. Typically the physician will stop the antibiotic that is suspected of causing the infection. About 25% of the time symptoms will improve 2 or 3 days later simply by discontinuing the antibiotic. If symptoms don’t improve, another antibiotic such as Fidaxomicin, Metronidazole, or oral Vancomycin are prescribed. These are three of the antibiotics known to be effective in the treatment of C. diff. The treatment period generally lasts 10-14 days.

Probiotics are generally encouraged. Probiotics can be hard on a patient’s stomach at first, so nurses should take care to monitor the patient carefully during this period. Staying hydrated and decreasing wheat and milk products temporarily can help as well.

Recurrence

Recurrence is common. It is considered a recurrence when symptoms have completely subsided while on appropriate therapy only to be followed by another bout of symptoms when treatment has been stopped. This can happen multiple times, and the care plan may need to be changed as to permanently address the problem.

References:

DePestel, Daryl D et. al. (2013). Epidemiology of Clostridium difficile. J Pharm Pract., 26 (5), 464-475. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128635/. 

Nearly half a million Americans suffered from Clostridium difficile infections in a single year. (2015). Retrieved from https://www.cdc.gov/media/releases/2015/p0225-clostridium-difficile.html. 

VK Viswanathan, MJ Mallozzi, and Gayatri Vedantam. (2010). Clostridium difficile infection: An overview of the disease and its pathogenesis, epidemiology and interventions. Gut Microbes., 1 (4), 234-242. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3023605/.