Clostridium Difficile
Introduction
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Clostridium difficile, or C.Diff, is a bacteria that causes severe antibiotic-associated diarrhea. This is because its great at colonising the gut after normal bowel flora are disrupted by broad-spectum antibiotics. It can then produce inflammatory toxins in the large bowel, resulting in foul smelling watery stools.
Coming
microbiology of this bacterial pathogen.
C.diff is a bacteria which is anaerobic and gram-positive. Outside of the colon, it survives in a spore form.
This is resistant to heat, acid, and antibiotics. Infection is highly transmissible via the fecal-oral route by ingestion of these spores.
Meanwhile, inside the colon, the bacteria can convert into a functional, toxin producing form which is susceptible to antibiotics.
C.Diff can produce two toxins: Toxin A which an enterotoxin and toxin B which is a cytotoxin. Together, they can disrupt the epithelial cell barrier and cause the formation of pseudomembranes. These are whitish-yellow plaques in the colonic mucosa which can grow larger and coalesce to cover the entire colon wall.
pathophysiology by looking at the three events essential for developing the infection.
Firstly, exposure to antibiotics. This is because they can disrupt the barrier function of normal colonical microbiota, providing a niche for the bacteria to multiply. The most frequently implicated are fluoroquinolones, clindamycin, and broad-spectrum cephalosporins.
The second essential event is exposure to a toxigenic form of C. difficile. This is most often acquired in hospital, with the rate of faecal colonisation increasing proportionally with the length of stay. It’s important to note that asymptomatic colonisation is very common and might be because the strain they have does not produce a toxin.
Finally, the host’s immune response to the toxin determines if a patient becomes symptomatic. If a patient has a high level of antibodies against C.diff toxins, then they are much less likely to develop diarrhoea.
The diagnosis of a C.diff infection can be made if there are clinical features plus either microbiological evidence of disease or pseudomembranous colitis:
Firstly, microbiological evidence of toxin producing c.diff found in stools. This can be achieved with a positive nucleic acid amplification test (NAAT) for a C. toxin gene or a positive stool test for the C. difficile toxin itself.
Secondly, a colonoscopy with findings that demonstrate pseudomembranous colitis. This is a more advanced form of the disease and is visualized at endoscopy in only ~50% of patients. In general, endoscopy is a rapid diagnostic tool only used in seriously ill patients with suspected infection. Remember, pseudomembranes manifest as raised yellow or off-white plaques up to 2 cm in diameter scattered over the colonic mucosa.
Other investigations are also important to consider. Look at blood tests like an EUCs to check if a patient has any renal impairment. Moreover, unexplained leukocytosis is a key clue for a c.diff infection, incredibly, a white blood cell count of 40,000 cells/microL or higher is possible in a fulminant colitis.
Additionally, consider imaging . The infection can cause a megacolon or ileus, so order an abdominal xray or CT. The "accordion sign" is highly suggestive of pseudomembranous colitis; it consists of mucosal inflammation involving the large bowel and is seen when orally administered contrast becomes trapped between thickened haustral folds.
consider three different scenarios.
Firstly, a primary C.diff infection.
You should always consider rehydration when treating any infection. Diarrhoea can cause people to be severely intravascularly depleted and can often cause an array of electrolyte derangements.
After this, you should also stop any implicated antibiotics that caused the infection unless there is a strong rationale for continuing them. Symptom resolution can occur in up to 25% of cases after, and the likelihood of relapse is reduced.
In terms of antibiotics to treat the actual infection, the first line is either metronidazole or oral vancomycin. Interestingly, oral, unlike IV vancomycin does not need any serum concentration monitoring. This is because oral vanc does not absorb well into the systemic circulation, which in a way is perfect for this kind of infection that is limited to the GIT.
Moving on, recurrent or refractory disease.
Our actual definition of recurrence is an infection occurring within 2 months of the resolution of symptoms from a previous episode. On the other hand, refractory disease is defined as lack of clinical improvement following 3 to 4 days of recommended therapy.
In these cases, further antibiotics should be considered in the form of another round of oral vancomycin or step-up to fidaxomicin. Fidaxomicin inhibits bacterial RNA synthesis by binding to RNA polymerase
If this does not work, faecal microbiota transplantation is the preferred treatment for second and subsequent recurrences or ongoing refractory disease. Now this stool transplantation is given through a nasoduodenal tube, although it can also be administered via a colonoscopy or frozen stool in oral capsules. Keep in mind, we are essentially asking someone to orally ingest someone else’s stool and you can imagine there are considerable logistical issues to think about including consent, donor screening, processing, and dosing so it’s usually only done in specialist centres.
Finally, let’s consider the management of a severe infection.
Core principles include resuscitation, supportive care, close monitoring, antibiotic therapy, consideration for faecal microbiota transplantation and most importantly, surgical intervention in the form of a colectomy if necessary.
A new onset of diarrhoea, often defined as 3 or more unformed stools in 24 hours, is the most important and common complaint. The stools are never grossly bloody but are classically watery. The bowel motions have a characteristic foul-smelling odour.
Abdominal pain can vary significantly from mild discomfort to be intense pain. Other features like fever, nausea and vomiting can also be present.
Its important to realise that C.Diff infections can vary in severity.
Severe infection is defined as any of the following: leucocytosis, severe abdominal pain, or elevated serum creatinine.
This can progress into fulminant colitis, previously described as severe, complicated C.diff infection. This is characterised by either severe hypotension and shock, acute ileus with little diarrhoea, or a megacolon, defined as a bowel dilatation >12 cm in the caecum.
The management or step-up therapy for C.diff is
vancomycin, fidaxomicin, then transplant stools-in.
I’ve also got a way to remember the definition of fulminant colitis. This is when there is shock, the bowels stop or get bigger than Bangkok. This highlights that shock, an ileus or the development of a massive megacolon, are the key features to look out for. To manage this, you might need a chop in surgery.