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Pseudomembranous colitis or Clostridium difficile associated disease (CDAD)

Discuss pathogenesis of CDAD?

Nearly all cases follow antibiotic use and shows changes restricted to the colon. Occasionally methotrexate can cause CDAD and an occasional case can occur in the absence of antibiotic use.  Major inducing agents are clindamycin, ampicillin & cephalosporins. Less problematic are sulphonamide, septrin, aminoglycosides etc.

Antibiotics disturb the normal gut flora, some more than others. The spores of C. difficile are the transmissible form and contaminate the environment, where they survive for long periods. The ingested spores germinate in the disturbed gut. The C. difficile bacteria produce two principal toxins – A and B – which cause diarrhoea and colitis. Toxin A & B- both pathogenic and strains produce both. The attack rate is variable (greater in older patients).

Discuss the clinical features of CDAD?

  • Diarrhoea except in presence of ileus. In 2-8% CD toxin is positive in the absence of diarrhoea. Healthy neonates can have CD toxin.
  • Stool examination may show occult blood, but grossly bloody stools are unusual

The clinical presentation however can vary from mild diarrhoea to severe colitis with dehydration, pseudomembranous colitis, megacolon and perforation.
It is rarely a segmental disease and pseudomembranes are often distributed throughout the colon. There are multiple yellowish white plaques- the intervening mucosa appears normal or shows hyperaemia or edema. The distal colon is involved in most patients- so sigmoidoscopy is usually adequate, but as many as one third of patients have lesions restricted to the right colon, necessitating colonoscopy for detection.

How do you assess the severity of CDAD?

Assess the severity of CDAD as follows:

  • Mild CDAD is not associated with a raised WCC; it is typically associated with <3 stools of types 5–7 per day on the Bristol Stool Chart.
  • Moderate CDAD is associated with a raised WCC that is <15 x 10^9/L; it is typically associated with 3–5 stools per day.
  • Severe CDAD is associated with a WCC >15 x 10^9/L, or an acute rising serum creatinine (i.e. >50% increase above baseline), or a temperature of >38.5°C, or evidence of severe colitis (abdominal or radiological signs).  The number of stools may be a less reliable indicator of severity. C
  • Life-threatening CDAD includes hypotension, partial or complete ileus or toxic megacolon, or CT evidence of severe disease.

Discuss diagnosis of CDAD?

Do not retest for C. difficile toxin (CDT) positive cases if patients are still symptomatic within a period of 28 days unless symptoms resolve and then
recur and there is a need to confirm recurrent CDI. B
More than one test per patient may be required if the first test is negative but where there is a strong clinical suspicion of CDI. Retest a second sample
24 hours later. Further tests might be necessary in light of clinical evidence.

Discuss management of CDAD?

  • Isolate the patient
  • Discontinue implicated antibiotic. When antibiotic treatment need to be continued- use antibiotics that were not implicated in the individual case and are unlikely to produce this complication- aminoglycosides, macrolides, sulphonamides, septrin etc.
  • Treatment is according to severity:

Mild and moderate CDAD – oral metronidazole 400–500 mg tds for 10–14 days. A

Severe CDAD – oral vancomycin 125 mg qds for 10–14 days. In severe CDAD cases not responding to oral vancomycin 125 mg qds, high-dosage oral vancomycin (up to 500 mg qds, if necessary administered via a nasogastric tube) +/- intravenous metronidazole 500 mg tds is recommended. The addition of oral rifampicin (300 mg bd) or IV immunoglobulin (400 mg/kg- one dose, consider repeating) may also be considered. C

Life-threatening CDAD – oral vancomycin up to 500 mg qds for 10–14 days via nasogastric tube or rectal installation plus IV metronidazole 500 mg tds.
Such patients should be closely monitored, with specialist surgical input, and should have their blood lactate measured. 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. (intracolonic vancomycin 500 mg in 100–500 ml saline 4–12-hourly given as retention enema: 18 gauge Foley catheter with 30 ml balloon inserted per rectum; vancomycin instilled; catheter clamped for 60 minutes; deflate and remove)

NB- None of the treatment should be considered a failure without a week’s trial. Fever usually resolves in 24-48 hrs and diarrhoea in 1-13 days with a mean of 3-4 days.

Discuss treatment of persistent diarrhoea?

If diarrhoea persists despite 20 days’ treatment but the patient is stable and the daily number of type 5–7 motions has decreased, the WCC is normal, and
there is no abdominal pain or distension; the persistent diarrhoea may be due to post-infective irritable bowel syndrome. The patient may be treated with
an anti-motility agent such as loperamide 2 mg prn (instead of metronidazole or vancomycin). The patient should be closely observed for evidence of a
therapeutic response and to ensure there is no evidence of colonic dilatation.

Discuss treatment of recurrent diarrhoea?

Recurrence occurs in about 20% of cases and 50-60% of cases after the second episode.

For first recurrence, repeat the same antibiotic used to treat the initial episode (unless the first episode was treated with metronidazole and the recurrence is severe CDAD, in which case vancomycin should be used). B

For subsequent recurrences, use vancomycin 125 mg qds.

For multiple recurrences- especially if evidence of malnutrition, wasting etc- options include-

  • Review all antibiotic and other drug therapy (consider stopping PPI and/or other GI active drugs)
  • Consider supervised trial of antimotility drugs (if no abdominal symptoms and not severe CDAD)
  • Tapering followed by pulsed doses of vancomycin may be of value. There are various regimens, such as 125 mg qds for one week, 125 mg tds for one week, 125 mg bd for one week, 125 mg od for one week, 125 mg on alternate days for one week, 125 mg every third day for one week (six weeks in total).
  • Oral vancomycin 125 qds plus rifampicin 300 mg BD for 2 week (no robust evidence)
  • IV immunoglobulin, especially if albumin status worsens.
  • Donor stool transplant- A fresh stool (30–50g) from a healthy donor is administered in normal saline by enema, slurries via nasogastric tube, or colonoscopy.

What is the role of probiotics?

Meta-analyses have failed to demonstrate statistically any significant efficacy in treating or preventing CDAD

Reference

  1. UK Department of Health guidance on Clostridium difficile infection: how to deal with the problem



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