Clostridioides difficile infection: Clinical sciences

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Introduction0:00–1:03

Clostridioides difficile infection, or CDI, is an infection caused by the organism Clostridioides difficile, or C. difficile for short.
Infection typically occurs through the fecal-oral route, by ingestion of spores found on contaminated surfaces, in soil, in water, or even on unwashed hands.
Once the spores reach the intestines, the GI flora, or microbiota, protects the gut and doesn’t allow C. difficile to proliferate.
But, if the diversity of GI flora is disrupted, often by recent antibiotic use, as well as proton pump inhibitors, or hospitalization, C.
difficile can overgrow and infect the colon. As a result, it starts producing toxins A and B, which can damage the gastrointestinal mucosa and eventually cause an inflammatory condition called pseudomembranous colitis.
The presentation can range from non-severe disease to severe or even fulminant infection.Now, if you suspect CDI, the first thing you should do is an ABCDE assessment, to determine if your patient is unstable or stable.

Unstable patients1:03–2:46

If the patient is unstable, stabilize the airway, breathing, and circulation, which typically requires obtaining IV access, resuscitating with IV fluids, and intubating the patient if you need to secure the airway.
Once you stabilize the patient, obtain a focused history and physical examination, and order labs, including CBC, CMP, and lactic acid.
History typically reveals watery diarrhea, usually more than 3 loose stools in 24 hours, which might be associated with mucus or blood, while some may present with ileus.
Additionally, individuals may report lower abdominal pain, fever, lethargy, and confusion, as well as recent or current antibiotic use.
Physical examination might reveal abdominal distention and tenderness, decreased bowel sounds, and hypotension. Some individuals can present with altered mental status or even shock.
Finally, lab results may show an elevated WBC count, serum creatinine, and lactic acid. Now here’s a high-yield fact!
If you suspect CDI in any patient, initiate contact precautions to avoid spreading the infection, and discontinue any inciting antibiotics if possible.
You should wash your hands with soap and water before and after patient contact. Remember to avoid using alcohol-based sanitizers, as C.
difficile spores are extremely resistant to alcohol.Alright, now, let’s move on to CDI testing. First, you need to obtain a liquid stool sample, but if there’s minimal diarrhea you can also do a rectal swab.

CDI testing2:46–5:48

Next, send the sample for a glutamate dehydrogenase antigen test, and C. difficile toxins A and B.
If both tests come back negative, rule out CDI and consider an alternative diagnosis. On the flip side, if both tests come back positive, it confirms CDI.
However, some individuals can have one positive and one negative test, meaning that the results are inconclusive. In this case, order a nucleic acid amplification test, or NAAT for short, to confirm the result.
A positive NAAT testing confirms CDI.Now, severe clinical manifestations in combination with positive CDI testing can confirm the diagnosis of fulminant CDI, so start supportive care with IV fluids and electrolyte replacement.
Additionally, put the patient on complete bowel rest and give total parenteral nutrition or TPN as required. If needed, place a nasogastric tube to access the stomach and relieve upper gastrointestinal distention.
Finally, start antibiotics, such as oral or nasogastric vancomycin plus IV metronidazole. Here’s a high-yield fact to remember!
Oral metronidazole is mostly absorbed in the small bowel. But in individuals with non-severe disease, enough will make it to the colon to treat the infection.
However, individuals with fulminant CDI might have ileus, which means not enough oral metronidazole will make it to the colon, so IV is the preferred route.
On the other hand, oral vancomycin will make its way to the colon without being absorbed, so it’s typically a good choice for all severities of CDI.
Alternatively, if patients on antibiotics don’t improve, they might benefit from a fecal microbiota transplant, which is basically putting stool from a healthy donor into the patient's gut, typically through colonoscopy or oral capsule.
This helps replenish the healthy microbiota, which is protective against C. difficile infection.Now that you’ve initiated the treatment, you should assess your patient for complications like toxic megacolon or colon perforation.
To do this, order a CT scan of the abdomen and pelvis. First, the typical colonic manifestation of CDI is pseudomembranous colitis.
On CT, this will show up as bowel wall submucosal edema and pericolonic stranding, which is called the accordion sign as it looks like the folds of an accordion.
When it comes to complications, if there’s colonic dilation greater than 6 cm or cecum dilation greater than 9 cm, you should suspect toxic megacolon.
On the other hand, if CT reveals free air in the abdomen, you need to think about a possible perforated colon. If you suspect either of these complications, the next step is to call surgery for emergent evaluation.Now let’s go back to the ABCDE assessment and discuss what to do in stable individuals.

Stable branch5:48–7:01

Start by obtaining a focused history and physical examination, as well as labs, such as CBC and CMP. As in unstable patients, history typically reveals watery diarrhea, lower abdominal pain, nausea, anorexia, and fever.
Also, patients might report a recent hospitalization or history of antibiotic use, usually within the prior 2-10 weeks. Common physical examination findings include abdominal distention and tenderness; while lab findings might include leukocytosis and elevated serum creatinine.
This is enough to suspect CDI, so make sure to initiate contact precautions and discontinue inciting antibiotics if possible.
Next, send stool samples for glutamate dehydrogenase antigen and C. difficile toxins A and B testing.
Negative results rule out CDI, so you should consider an alternative diagnosis; while positive results confirm CDI. In inconclusive cases, you can check NAAT to confirm or rule out CDI.
Alright, once you confirm the diagnosis of CDI, the next step is to determine the severity, based on WBC count and serum creatinine, indicate the non-severe type of CDI.

Non-severe CDI7:01–7:55

In these individuals, start supportive care with IV fluids, electrolyte replacement; and a low-residue diet, which includes food that’s easy to digest.
In other words, with a low-residue diet, less undigested food reaches the colon, which eventually results in fewer stools.
Additionally, give antibiotics, like oral fidaxomicin or vancomycin, for 10 days. Remember that fidaxomicin is preferred due to its lower recurrence rate.
If these antibiotics are not available, then you can use oral metronidazole. On the other hand, a WBC count of 15000 cells/ml or greater; OR a serum creatinine of 1.5 mg/dl or greater, indicate severe type of CDI.

Severe CDI7:55–8:32

In this case, in addition to IV fluids and electrolytes, you should put the patient on complete bowel rest, with TPN and nasogastric decompression if needed.
Finally, start antibiotics, ideally oral fidaxomicin, for 10 days, but you can use oral vancomycin if it’s not available.
Keep in mind that metronidazole is no longer the first line treatment for severe CDI. Okay, now that you’ve initiated treatment, the next step is to assess the patient’s therapeutic response.
If symptoms persist despite treatment, you should consider an alternative diagnosis. However, if symptoms resolve completely while on treatment, then reappear within 2 months, you should suspect recurrent CDI.

Assessing the response8:32–9:29

In these individuals, obtain stool samples for C. difficile testing.
If the results are positive, your patient has recurrent CDI, so start antibiotic treatment with oral fidaxomicin or vancomycin.
Additionally, you can add bezlotoxumab as an adjunct to the antibiotics, especially if this is the patient’s second recurrence.
If this is not available, you can treat them with a combination of oral vancomycin and rifaximin. Finally, if this is the patient’s third or higher recurrence, you should consider fecal microbiota transplantation.Alright, as a quick recap… If you suspect CDI, the first thing you should do is an ABCDE assessment, to determine if your patient is unstable or stable.
Unstable individuals should be stabilized and tested for CDI using stool GDH antigen, toxins A and B, or NAAT testing. Unstable patients typically present with fulminant CDI and require treatment with antibiotics and supportive care, which includes IV fluids and electrolytes, bowel rest, TPN, and NGT decompression.

Recap9:29–10:59

Additionally, discontinue any inciting antibiotic if possible, and use a CT scan to assess for complications like toxic megacolon or perforation.
Similarly, in stable patients with suspected CDI, proceed with CDI testing and determine the severity using WBC count and serum creatinine.
Non-severe CDI requires treatment with IV fluids, electrolyte replacement, a low-residue diet, and antibiotics, preferably fidaxomicin.
On the other hand, individuals with severe CDI require IV fluids, electrolytes, antibiotics, and if needed, complete bowel rest, TPN, and nasogastric decompression.
In both cases, symptoms might resolve and reappear within 2 months, which is called recurrent CDI. The first and second recurrences of CDI are treated with antibiotics.
However, a third or higher recurrence might require fecal microbiota transplantation in addition to antibiotics and bezlotoxumab.
decompression In both cases symptoms might resolve and reappear within two months which is called recurrent CDI The 1st and 2nd Recurrences of CDI are treated with antibiotics However a third or higher recurrence might require fecal microbiota transplantation in