Clostridium difficile (Pseudomembranous colitis)

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Clostridium difficile is difficult to treat, hence the name. Clostridia, as a family, are obligate anaerobes, meaning they don’t require oxygen to thrive, in fact, they’re better off without it.
In nature, they thrive in deep, compact soil, and when they feel the stress of fresh oxygenated air, they often produce spores, which are extremely resilient to the environment.
When conditions improve, the spores can sprout into fully fledged Clostridia. In the lab, when doing a gram stain, Clostridium difficile is gram positive, or purple and look like big cylinders or rods.
Now, Clostridium difficile can sometimes establish residence in our colon typically after a person has accidentally ingested the bacteria that originally were living in another person’s colon.
This is called the fecal-oral route, and it usually results from eating with unwashed hands. In fact, around 5% of population are asymptomatic carriers of Clostridium difficile, but the vast majority of these individuals don’t seem to have an issue with it!
That’s because there are a number of bacterial species living in the intestines that make up the microbiome. These various bacterial species called the normal flora, coexist in an environment where they live together and compete for resources.
A healthy normal flora, therefore doesn’t allow Clostridium difficile to dominate the intestines. However, if the diversity of that normal flora is disturbed - by antibiotics - for instance, then organisms that are resistant to antibiotics like Clostridium difficile can thrive while other bacteria might die out.
That can allow for overgrowth of Clostridium difficile. Another way to disturb the equilibrium of the gut biome is use of chemotherapy or prolonged use of elemental diet, which is gastric tube feeding of elemental liquid nutrients, often seen in intensive care units.
In these situations, once again, the normal flora gets disturbed and it tilts the equilibrium towards Clostridium difficile.
Combinations of high antibiotic usage and parenteral feeding make Clostridium difficile a common problem in intensive care units and nursing homes.
Now in infants, it turns out that many have Clostridium difficile without having disease - so it’s unclear if colonized infants need to be treated for Clostridium difficile at all.
Now, Clostridium difficile’s main pathogenic mechanism is the production of various toxins, which it uses to help establish itself within the intestines, primarily within the colon.
The first is Clostridium difficile toxin A, or TcdA, which is a highly potent enterotoxin, that destroys the cytoskeleton within an intestinal cell.
This causes the intestinal cells to undergo apoptosis or programmed cell death. If enough of intestinal cells die, the tight junctions between neighboring cells fall apart.
The damaged intestinal tissue begins to get porous or leaky, and that causes a strong inflammatory response from the immune system.
Neutrophils begin to infiltrate the intestine, and they’re greeted by an additional toxin called Clostridium difficile toxin B, or TcdB, which is a cytotoxin.
TcdB enters cells, including neutrophils, and causes cellular apoptosis. The combined effect of the two toxins leads to pseudomembranous colitis.
On colonoscopy, the result of the inflammatory response is the formation of elevated, yellowish-white plaques called pseudomembranes, which are filled with pus.
Symptoms of Clostridium difficile infection most commonly include diarrhea with or without mucus and blood, abdominal pain, and a high fever.
If left untreated, the infection can lead to a toxic megacolon, which is where the colon gets very dilated, to the point of rupture.
If there’s an intestinal rupture or perforation, it can lead to septic shock, and even death. Diagnosis is usually confirmed by stool testing for the presence of C.
difficile toxins. This is done by enzyme linked immunosorbent assay, or ELISA.
An individual with an active infection, will usually test positive for Clostridium difficile toxins A and B. Colonoscopy or sigmoidoscopy can be used to confirm the diagnosis by visualising the pseudomembranous appearance.
Now because antibiotics can cause Clostridium difficile to take hold, it’s important to discontinue any offending antibiotics as soon as possible.
Having said that, the treatment of Clostridium difficile infection also includes antibiotics that are specifically effective against Clostridium difficile like metronidazole, which is used in mild to moderate disease; and vancomycin, which is usually reserved for severe disease.
These antibiotics are usually taken orally, so that they function primarily within the gut. Individuals are also given oral rehydration therapy to help with the diarrhea.
It’s important to avoid using medications that slow the course of diarrhea, like loperamide, because that can worsen the disease.
If antibiotics aren’t effective, an alternative treatment for prolonged and recurrent C. difficile infections is a fecal transplant.
The idea is pretty solid. Basically, it starts with obtaining a feces sample from a healthy donor - usually a family member, which contains within a sample of a fully balanced intestinal flora.
The fecal sample is given to an individual with C. difficile either by an nasogastric tube or by an enema, and once the fecal transplant is done, the healthy flora begin to compete with C.
difficile, reducing its numbers and toxin production. Along the same lines, probiotics containing organisms like lactobacillus and Saccharomyces boulardii yeast are used to help prevent and supplement the treatment of pseudomembranous colitis.
Now, like most things - prevention is better than a cure. And healthcare facilities work hard to isolate individuals with Clostridium difficile infection so that it doesn’t spread to others.
Health care providers typically use contact precautions like gowns and gloves, as well as cleaning their hands with soap and water rather than hand sanitizers to help avoid spreading the highly resistant spores from one person to another.
Surfaces are cleaned with cleaning agents like a mix of one part sodium hypochlorite, or household bleach, to ten parts water.
This is then used to clean surfaces and objects like elevator buttons, light switches, taps, and the toilet area. All right, as a quick recap.
Clostridium difficile is a sporulating, Gram positive obligate anaerobe. When the microbiome is altered, by changes like the use of antibiotics, the bacteria becomes dominant and secretes toxins A and B which cause intestinal damage.
The overgrowth of Clostridium difficile leads to pseudomembranous colitis, which results in diarrhea with or without mucus and blood, abdominal pain, and a high fever.
Treatment options include antibiotics, or fecal transplant, whose goal is to reestablish the normal flora, and to keep the growth of C.
difficile in check. In healthcare settings its important to isolate affected individuals, use contact precautions, wash hands with soap and water, and wiping down surfaces with sporicidal cleaning agents.