Topics / Medical / Diarrhea and Electrolytes

Summary This article discusses diarrhea caused by C. difficile which commonly presents in patients who have been exposed to antibiotics. The gold standard test is an immunoassay for C.difficile toxins and C. difficile PCR. The patients may be complicated with infectious colitis (pseudomembranous colitis), toxic megacolon, perforation of the bowel, and sepsis. The treatment includes: Infection control, fluids, and treating the patient with metronidazole or vancomycin. Patients in which we suspect a complication may require a surgical consult. Loperamide is contraindicated because it may result in toxic megacolon.

Basics

This diarrhea is caused by Clostridium difficile. It is not a normal bowel commensal, but it is sometimes found to colonize the gastrointestinal tract. The normal gut flora ensures that C. difficile does not cause any disease. When patients use antibiotics, this may lead to an imbalance in the normal GIT flora. This imbalance allows C. difficile to quickly multiply and release toxins. Hence, patients presenting with watery diarrhea, abdominal pains, and fever with a history of antibiotics (especially within 6 weeks of presentation) should increase your level of suspicion.

C. difficile is highly infectious, and patients should ideally be isolated and surfaces thoroughly cleaned. C. difficile, a gram-positive anaerobic, spore-forming bacteria is spread via the fecal-oral route. It produces toxins: Toxin A and toxin B. The bacteria results in diarrhea and inflammation of the colon (“colitis”) due to the release of enterotoxins (toxin A) and cytotoxin (toxin A). The colonic mucosa may become covered by a pseudo-membrane (composed of fibrin) and hence the name, “pseudomembranous colitis.”

The EML guidelines state that patients with “unexplained and new-onset diarrhea of more than 3 unformed stools in 24 hours should be tested” for C. difficile. This probably refers to a patient which has been admitted/has risk factors and develops diarrhea during their admission. They go on to further note that, “Repeat testing (within 7 days) is not recommended.”

Some differentials: Inflammatory Bowel Disease (Ulcerative colitis, Chron’s disease), Diverticulitis

Risk Factors

Medications: Antibiotic use (Penicillins, Cephalosporins, Fluoroquinolone, Clindamycin), Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, Chemotherapy
Hospitalization: Recent, Prolong, ICU stay
Conditions: Chronic Kidney disease, Chronic Liver disease, Gastrointestinal Surgery, Inflammatory Bowel Disease
Devices: Feeding tubes
Patient: Advanced age > 65

Presentation

Low-grade fever
Anorexia, Nausea, Vomiting
Abdominal pains
Abdominal distension
If complicates: Signs of sepsis, signs of peritonitis (due to perforated bowel), findings suggestive of toxic megacolon

Investigations

WCC and other inflammatory markers become raised
Urea+Electrolytes + Creatinine, assess hydration and renal function
Stools: C. difficile: Should request immunoassay for C. difficile toxin A and B, and C. difficile PCR. Elevated WBC in stools. Microscopy and Culture for other micro-organisms should also be performed.
Additional investigations: Imagining (Abdominal X-ray) and endoscopy (colonoscope) should be performed in patients where fulminant colitis or any other differential diagnosis is suspected.
1. Abdominal X-Rays: (C. difficile colitis)
  1. Earlier: Not many findings
  2. Later: Bowel dilatation, Mural thickening, Thumb printing
  3. Complicated: Signs of Toxic Megacolon (The colon becomes extremely dilated, the transverse colon > 6cm) and Perforation (Air under the diaphragm on erect CXR)
2. Other investigations discussed on another article. Read more on C. difficile colitis on Radiopedia.

Case courtesy of Dr Jayanth Keshavamurthy, Radiopaedia.org. From the case rID: 46188
"Gas pattern: No supine evidence of free peritoneal air. There is a mucosal thickening demonstrated by the thumbprinting sign in the ascending colon. There is a paucity of bowel gas in the descending colon. However correlating with the CT abdomen, likely favors diffuse colitis with a paucity of bowel gas in this region. No toxic megacolon."

Case courtesy of Assoc Prof Craig Hacking, Radiopaedia.org. From the case rID: 79194
"Increase in gaseous distension of the distal transverse colon, now measuring up to 80 mm in diameter (2 days ago was 60 mm). The transverse colon and sigmoid colon are both featureless consistent with severe colitis. There is fecal loading in the right side of colon. No evidence of free gas or pneumatosis intestinalis. The appearance is concerning for toxic megacolon."

Management

Patients that are asymptomatic do not require treatment.

Non-Pharmacological

NB: Infectious control measures! – this infection is very infectious. These patients need to be placed under contact precaution. This contact precaution is maintained for at least 48 hours after diarrhea has resolved. One needs to remember that alcohol-based sanitizers do not really kill the spores so one should perform regular hand washing with soap and water.
Discontinue all antibiotics, and only prescribe the ones under “pharmacological.”
Promote oral hydration if possible (ORS), unless the patient does not tolerate this.
If diarrhea does not resolve when the antibiotics are removed, then one should definitely begin pharmacological treatment.

Pharmacological

Fluids, oral fluids or IV fluids to rehydrate the patient.
Medication
1. Antibiotics:
  1. Mild-Moderate: Metronidazole 400mg PO 8 hourly for 10 days
  2. Severe: Vancomycin 125mg PO 6 hourly for 10 days.
    1. NB: These are for patients which are septic, WCC > 15, Creatinine > 132, Age >65, Immunodeficiency, ICU admission
    2. The reason Vancomycin is given PO and not IV is because IV Vancomycin will NOT be secreted into the colon and hence will have little to no therapeutic effect
  3. Extremely Severe:
    1. 1. Patient has an ileus OR Toxic megacolon OR Shock/hypotension
      2. Treat with Vancomycin 12mg PO 6 hourly for 10 days AND Metronidazole 500mg PO 8 hourly for 10 days (may switch to oral Metronidazole when possible).
      3. Side Note: NG tube should be inserted, surgical consult should be done, if there is an ileus then rectal Vancomycin can be used, these patients may require surgery to remove part of the colon.
  4. Recurrence:
    1. If Metronidazole was used during the first episode, then give Vancomycin PO 125mg 6 hourly for 10 days. OR
    2. If Vancomycin was used during the first episode, then either give Vancomycin as a tapered and pulse regime. (Vancomycin 125mg PO 6 hourly for 10 days, then 12 hourly for 7 days, then once daily for 7 days, then every 2^nd – 3^rd day for 2-8 weeks.)

Warning Loperamide is contraindicated because it may result in toxic megacolon.

Complications

Pseudomembranous colitis – this will be visualized on endoscopy
Toxic megacolon – this is a complication in many forms of “colitis”, such as inflammatory bowel disease, infectious colitis, and other forms of colitis. Should actually be called “Toxic colitis” instead of Toxic megacolon since the bowel loops are not always dilated.
Perforation of the colon
Sepsis
Death

Referral

If there any of the complications above (Pseudomembranous colitis, Toxic megacolon, Perforation, hypotension-requiring vasopressors) is suspected, then a surgical consult should be done.
If the patient does not improve within 5 days of therapy then the patient should be referred to a higher level of care.

References and Further Reading 1. The National Department of Health, South Africa: Essential Drugs Programme. Primary Healthcare Standard Treatment Guideline and Essential Medicine List. 7th ed. South African National Department of Health; 2020.
2. Mada PK, Alam MU. Clostridioides Difficile. [Updated 2022 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/ books/ NBK431054/

Published on 2 August 2022

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C. Difficile Diarrhea