Question 19

a)    Outline the specific diagnostic investigations for:

i.    Clostridium Difficile Infection (CDI).
ii.    Complications of CDI.    
(30% marks)

b)    List the features of severe CDI.    
(10% marks)

c)    Discuss the management of CDI, with specific reference to severity and episode (first/recurrence).
(60% marks)

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College answer

Not available.


Specific diagnostic investigations:

  • Stool PCR for C.difficile toxin A or B
  • Enzyme immunoassay for C.difficile GDH antigen
  • Nucleic acid amplification test (NAAT) for C. difficile toxin gene
  • Cell culture cytotoxicity assay
  • Selective stool anaerobic culture confirming toxin-secreting C.difficile organisms

Investigations for complications of CDI:

  • Blood biochemistry to look for end-organ damage, eg renal failure
  • Endoscopy, looking for pseudomembranous colitis
  • Colonic biopsy to confirm colitis
  • CT abdomen/pelvis looking for:
    • Small bowel obstruction, bowel dilatation
    • Mural thickening and haustral fold thickening ("thumbprinting")
    • Toxic megacolon
    • Perforation and free intraperitoneal gas

Features of severe CDI:    

  • Clinical features:
    • High fever, over 38.5º C
    • Toxic megacolon
    • An acute abdomen, peritonitis
    • Presence of ileus or evidence of bowel obstruction
  • Biochemistry
    • WCC > 15 
    • Raised lactate
    • Acute kidney injury (Creatinine increase by 50%)
    • Albumin < 25
  • Imaging:
    • Large intestine distension, colonic wall thickening, fat stranding, unexplained ascites 
  • Endoscopy:
    • The finding of pseudomembranous colitis


  • Mild-moderate CDI, first episode:
    • Oral metronidazole
  • Recurrent mild-moderate CDI:
    • First recurrence: treat in the same way as the first episode
    • Second recurrence: change to vancomycin or fidaxomicin; think about adding rifaximin
    • Third recurrence: consider a faecal microbiota transplant
    • Bezlotoxumab, a monoclonal antibody to the B toxin, is also recommended for severe and recurrent infections, particularly where the patient is immunocompromised. 
  • Severe and complicated CDI:
    • Oral vancomycin  (up to 500mg qid) +/- fidaxomicin +/- rifaximin +/- bezlotoxumab
    • Vancomycin enema in case of ileus
    • Consider surgery
    • Tigecycline, fusidic acid, rifampicin are alternatives


Leffler, Daniel A., and J. Thomas Lamont. "Clostridium difficile infection." New England Journal of Medicine 372.16 (2015): 1539-1548

McDonald, L. Clifford, et al. "Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)." Clinical infectious diseases 66.7 (2018): e1-e48.

Cheng, Allen C., et al. "Australasian Society for Infectious Diseases guidelines for the diagnosis and treatment of Clostridium difficile infection." Medical Journal of Australia 194.7 (2011): 353-358.