Question 3

a) List the patient-related risk factors associated with the development of Clostridium difficile enterocolitis
b) List two tests that can be used for diagnosis of Clostridium difficile enterocolitis.
c) List four markers of severity of disease in Clostridium difficile enterocolitis
d) What are other possible causes of infective diarrhoea in the critically ill?

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College Answer

a) Patient-related risk factors

  • Broad spectrum antibiotics in particular clindamycin, quinolones, amoxycillin, cephalosporins
  • Immunosuppressive therapy /Cytotoxic chemotherapy
  • Gastric acid suppression
  • Age > 65
  • Prolonged hospitalisation
  • Renal impairment
  • Prior GI surgery

b) Diagnostic tests

  • Faecal culture determination of the toxigenic status of the infecting C. difficile isolate
  • Screening EIA to detect C. difficile glutamate dehydrogenase (GDH)
  • EIAs to detect toxins A and/or B
  • Cell culture cytotoxicity assays that directly detect stool cytotoxic activity
  • PCR-based assays to detect conserved gene targets within the pathogenicity locus of C. difficile

c) Markers of severity

  • Clinical
    • Fever (> 38.5°C), rigors
    • Haemodynamic instability
    • Peritonitis or evidence of bowel perforation
    • Ileus or toxic megacolon
  • Laboratory
    • White blood cell count >15 × 109/L and < 20% neutrophils
    • Elevated lactate level
    • Rise in creatinine level (> 50% above baseline)
    • Albumin level < 25 mg/L
  • Other investigations
    • Large intestine distension, colonic wall thickening, fat stranding, unexplained ascites (imaging)
    • Pseudomembranous colitis (colonoscopy)

d) Other infective causes of diarrhoea

  • Viruses –Norovirus, adenovirus, CMV (rotavirus in children)
  • Bacterial pathogens – Campylobacter, E.Coli, cholera, salmonella Protozoa – Cryptosporidium, Giardia
  • Parasitic -Strongyloides


This question favours the candidate who has a very detailed understanding of C. difficile infection. A long rant about C.difficile is available in the Required Reading section.

The risk factors for C.difficile infection are discussed here, in a NEJM article.

Where did the college answer get its evidence from, you ask?

As for diagnosis of C.difficile, the current recommendations are:

  • PCR is better than toxin A or B identification
  • You should only test loose stools
  • You should not re-test

Markers of "severe" enterocolitis, which means the sort that ends up either killing you or results in a colectomy, are deliniated in this retrospective study. They are as follows:

  • age >70 years
  • maximum leukocyte count >20,000 cells/mL
  • minimum albumin level <25 g/L
  • maximum creatinine level >200 mcg/L
  • small bowel obstruction or ileus
  • CT evidence of colorectal inflammation

To this list, another study adds more markers of severity:

  • Fever (>38.0°)
  • Abdominal distension


Loo, Vivian G., et al. "Host and pathogen factors for Clostridium difficile infection and colonization." New England Journal of Medicine 365.18 (2011): 1693-1703.


Thomas, Claudia, Mark Stevenson, and Thomas V. Riley. "Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review." Journal of antimicrobial chemotherapy 51.6 (2003): 1339-1350.


Anand, Ajay, and Aaron E. Glatt. "Clostridium difficile infection associated with antineoplastic chemotherapy: a review." Clinical Infectious Diseases 17.1 (1993): 109-113.


Cunningham, R., et al. "Proton pump inhibitors as a risk factor for Clostridium difficilediarrhoea." Journal of Hospital Infection 54.3 (2003): 243-245.


Pépin, Jacques, Louis Valiquette, and Benoit Cossette. "Mortality attributable to nosocomial Clostridium difficile–associated disease during an epidemic caused by a hypervirulent strain in Quebec." Canadian Medical Association Journal 173.9 (2005): 1037-1042.


Cunney, Robert J., et al. "Clostridium difficile colitis associated with chronic renal failure." Nephrology Dialysis Transplantation 13.11 (1998): 2842-2846.


Surawicz, Christina M., et al. "Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections." The American journal of gastroenterology 108.4 (2013): 478-498.


Henrich, Timothy J., et al. "Clinical risk factors for severe Clostridium difficile–associated disease." Emerging infectious diseases 15.3 (2009): 415.


FujitaniMD, Shigeki, W. Lance GeorgeMD, and A. Rekha MurthyMD. "Comparison of clinical severity score indices for Clostridium difficile infection."Infection Control and Hospital Epidemiology 32.3 (2011): 220-228.