Diagnosis requires demonstration of the Clostridioides difficile toxin. The presence of Clostridioides difficile itself is not sufficient
| Initial Management Summary |
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- ABC, IV fluids, assess severity, send stool, Stop opiates and loperamide
- Mild disease oral Metronidazole 400-500 mg tds for 10-14 days
- Moderate/Severe Vancomycin 125 mg PO/NG qds for 10-14 days
- Failure try Fidaxomicin 200mg PO 12 hourly for 10 days
- Surgical review if toxic megacolon/perforation suspected
- If NBM then IV Metronidazole 500mg tds
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Isolation if an infective cause suspected. Gown up and wear gloves, which should be placed in the bin in the patient's room. Ensure hands washed with soap and water to remove any C. difficile spores.
About
- Clostridioides difficile is an anaerobic spore forming bacterium
- Now called Clostridioides difficile
- It is found in intestines.
- It can be found in healthy people, where it causes no symptoms
Characteristics
- Large gram-positive anaerobic terminal spore-forming rods
- Irregularly shaped colonies on blood agar
Source
- Found in the soil or in the bowel or in the environment as spores
- Cultured from stool of 3% of population
- Found in 30% of hospital patients and 66% of babies
- Pathogenicity when antibiotics kill off other gut bacteria
- This allows C. difficile to grow to unusually high levels.
- It also allows the toxin that some strains of C. difficile produce to reach levels where it attacks the intestines and causes mild to severe diarrhoea.
- It can lead to more serious infections of the intestines with severe inflammation of the bowel (pseudomembranous colitis).
Risks
- Antibiotics, particularly the elderly
- Those whose immune systems are compromised.
Aetiology
- Toxin A - an enterotoxin and cytotoxic acts on gut mucosa
- Toxin B - a cytotoxin that cause the death of colonic luminal cells
- Third substance that inhibits bowel motility
- Together these cause ulceration and diarrhoea
- Ribotype 027 is associated with a very virulent form of infection with higher toxin production and quinolone resistance
Antibiotics associated
- The use of broad-spectrum antibiotics is associated with PMC especially
- Ampicillin, Amoxicillin, 2nd/3rd generation Cephalosporin
- Clindamycin and quinolones
Pathology
- Colonic inflammation and mucosal damage
- Inflammatory exudate forms pseudomembranes
- Due to infection with Clostridioides difficile (CD)
Clinical
- Diarrhoea may begin within 4-10 days of antibiotic treatment but may be delayed up to 6 weeks
- Asymptomatic to mild diarrhoea to pseudomembranous colitis
- Copious liquid stool with Fever, malaise
- Abdominal pain and distension and toxic megacolon, perforation and death
Investigations
- FBC, U&E, LFT, AXR may suggest dehydration/prerenal failure
- CT Abdomen if needed
- C. difficile toxins A and B.
- Colonoscopy/Sigmoidoscopy may show yellow adherent plaques
- Anaerobic culture on cycloserine, cefoxitin and fructose (CCFA) media
- Stools - the presence of CD toxin A and B which may need repeated
- Stool culture to exclude other infective causes
- AXR/CXR exclude perforation, ileus, megacolon
Differentials
- Diarrhoea due to NG and PEG feeds
- Salmonella, Shigella, Campylobacter, E Coli 0157
- Viral Gastroenteritis
Complications
- Prerenal failure
- Toxic megacolon and Colonic perforation
Severity Assessment
- Mild
- WCC < 15 x 109/l
- < 5 stools per day of type 5-7 on Bristol stool chart
- Severe: any of these should suggest using oral vancomycin (or fidaxomicin) in preference to Metronidazole
- WCC > 15x 109/l
- an acute rising serum creatinine (i.e. >50% increase above baseline)
- a temperature of > 38.5 C
- evidence of severe colitis (abdominal or radiological signs)
- The number of stools is a less reliable indicator of severity.
- Life threatening CDI
- Hypotension
- Partial or complete ileus
- Toxic megacolon or CT evidence severe disease
Other markers of poor prognosis
- CDI due to ribotype 027 strains is associated with increased severity
- Elevated blood lactate >5 mmol/L even with colectomy
Management [Based on reference below]
- Isolate patient, hand wash with soap and water on suspicion before toxin result. Supportive care should be given, including attention to hydration, electrolytes and nutrition. Fluid resuscitation and management.
- Antiperistaltic agents should be avoided in acute infection. This is because of the theoretical risk of precipitating toxic megacolon by slowing the clearance of C. difficile toxin from the intestine. Avoid loperamide and similar. Stop any antibiotic if possible and stop PPI if possible.
- Mild: Patients with mild disease may not require specific C. difficile antibiotic treatment. If treatment is required, oral Metronidazole 400 mg TDS for 10-14 days as it has been shown to be as effective as oral vancomycin in mild to moderate CDI
- Moderate:For patients with moderate disease, a 10- to 14-day course of oral Metronidazole is the recommended treatment (dose: 400 mg TDS). This is because it is cheaper than oral vancomycin and there is concern that overuse of vancomycin may result in the selection of vancomycin-resistant enterococci
- Severe: Oral Vancomycin 125 mg QDS for 10-14 days. This is superior to Metronidazole in severe cases of CDI. Fidaxomicin should be considered for patients with severe CDI who are considered at high risk for recurrence; these include elderly patients with multiple comorbidities who are receiving concomitant antibiotics
- If severe cases not responding to oral Vancomycin then Fidaxomicin 200mg BD should be considered. Alternatively, high dosage oral Vancomycin (up to 500 mg QDS, if necessary administered via a nasogastric tube) plus IV Metronidazole 500 mg TDS is an option. Vancomycin levels not needed if it is given orally as no systemic absorption. The addition of oral Rifampicin (300 mg BD) or IV immunoglobulin (400 mg/kg) may also be considered.
- Life-threatening disease (i.e. hypotension, partial or complete ileus or toxic megacolon, or CT evidence of severe disease) can be treated by vancomycin given via a nasogastric tube (which is then clamped for one hour) and/or by rectal installation
- Surgical consult. Colectomy is required in some patients with megacolon (dilatation >10 cm), perforation or septic shock, and should be done before the blood lactate rises above 5 mmol/L. A recent systematic review concluded that total colectomy with end ileostomy is the preferred surgical procedure; other procedures are associated with high rates of re-operation and mortality. An alternative approach, diverting loop ileostomy and colonic lavage, has been reported to be associated with reduced morbidity and mortality.
- Recurrent disease occurs in about 20% of patients treated initially with either Metronidazole or vancomycin. The same antibiotic that had been used initially can be used to treat the first recurrence. A variable proportion of recurrences are reinfections (20-50%) as opposed to relapses due to the same strain; relapses tend to occur in the first two weeks after treatment cessation.
- Colectomy should be considered, especially if caecal dilatation is >10 cm. Colectomy is best performed before blood lactate rises > 5 mmol/L, when survival is extremely poor
- Donor faecal transplant
References