Question 3

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

Discussion

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?

• Broad spectrum antibiotics in particular clindamycin, quinolones, amoxycillin, cephalosporins

• Immunosuppressive therapy /Cytotoxic chemotherapy

• Gastric acid suppression

• Age > 65

• Prolonged hospitalisation

• Renal impairment

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.