Clostridium difficile is the most common cause of infectious diarrhoea in hospitalised patients. This anaerobic, spore-forming bacteria is prevalent in the environment and can be spread directly or indirectly via the faecal-oral route. C. difficile presents a challenge as the spores can survive in the environment for long periods and are resistant to many disinfectants.

Asymptomatic colonisation with C. difficile is common, particularly amongst hospitalised patients, nursing home residents, and infants. Symptomatic infection may then occur following a disruption of the host’s microbiome that favours C. difficile germination and growth. Antibiotic use is the most common cause of this disruption. While all antibiotics are thought to be capable of causing C. difficile infection (CDI), broad-spectrum antibiotics such as cephalosporins, quinolones, and lincosamides are associated with the highest risk. Other risk factors include hospitalisation, cancer chemotherapy, advanced age, and the use of proton pump inhibitors.

The C. difficile bacterium produces two exotoxins, toxin A and toxin B. Some strains also produce another toxin called binary toxin. Although binary toxin is sometimes associated with increased disease severity, its role is poorly understood. Toxins A and B damage the lining of the colon which can result in symptoms such as fever, watery diarrhoea, and abdominal pain. In more severe cases, the diarrhoea may be particularly frequent and lead to severe dehydration. Blood or pus may also be visible in the stools.

The Therapeutic Guidelines provide the following recommendations for the treatment of CDI.

  • First episode:
    • Metronidazole (orally or enterally), or
    • Vancomycin (orally or enterally)
  • First recurrence:
    • Vancomycin (orally or enterally), or
    • Fidaxomicin orally
  • Second and subsequent recurrences or ongoing refractory disease (adults):
    • Faecal microbiota transfer (if available),
    • Vancomycin (orally or enterally), or
    • Fidaxomicin orally
  • Second and subsequent recurrences or ongoing refractory disease (children):
    • Vancomycin (orally or enterally), or
    • Nitazoxanide orally.

All patients with severe disease require specialist review. The rate of severe CDI has been increasing in recent years and accounted for 2.2% of all CDI cases seen in Australian hospitals in 2015. Signs and symptoms of severe disease include leucocytosis, severe abdominal pain, elevated serum creatinine, elevated blood lactate, low serum albumin, high fever, or organ dysfunction. Outbreaks of hypervirulent strains have been reported in Australia since 2000.

A diagnosis of CDI continues to be associated with considerably longer hospital stays. The average length of stay for all CDI cases is reported to be 17.7 days, although there are marked differences for patients presenting with CDI as the principal diagnosis (7.9 days) compared to CDI as an additional diagnosis (21.6 days). This represents a significant increase in healthcare costs in addition to the increased morbidity and mortality associated with infection. Around 20% of patients with an initial infection will experience at least one other episode. Recurrent CDI is often more difficult to treat and associated with worse outcomes and higher costs than initial infections. Therefore, interventions that prevent recurrence are of great interest.

Bezlotoxumab is a new medication available for the prevention of C. difficile recurrence in adults who are at high risk. Bezlotoxumab is a monoclonal antibody that binds to toxin B with high affinity, neutralising its activity. Clinical trials demonstrate a sustained cure rate of 64% in patients treated with bezlotoxumab plus standard of care antibacterial therapy compared to 54% for standard of care therapy alone. The rate of adverse events was similar amongst the two groups; infusion-related reactions occurred in 10.3% of patients receiving bezlotoxumab (7.6% placebo). The other most commonly reported adverse events in each group include abdominal pain, diarrhoea, and nausea. Bezlotoxumab has a terminal half-life of around 19 days. This allows the use of a single infusion during a course of antibiotic treatment. As bezlotoxumab is not an antibacterial agent, it must be co-administered with appropriate antibacterial therapy.

Bezlotoxumab is not active against toxin A. However, it is thought that toxin B is the main determinant of virulence in recurrent CDI. Clinical studies of actoxumab, an experimental antibody against toxin A, support this idea. Actoxumab has not demonstrated efficacy when used as a single agent and does not improve efficacy when added to bezlotoxumab.

The role of bezlotoxumab in the management of C. difficile infection is currently uncertain. Further studies are required to determine the optimal timing of infusion and the patients most likely to benefit from this preventative therapy.


  1. Antibiotic Expert Group. Acute Infectious Diarrhoea. In: Therapeutic Guidelines: Antibiotic. Version 16. Melbourne: Therapeutic Guidelines; 2019.
  2. Australian Commission on Safety and Quality in Health Care. Clostridium difficile infection: 2016 Data Snapshot. Sydney: ACSQHC; 2018.
  3. Wilcox MH, Gerding DN, Poxton IR, Kelly C, Nathan R, Birch T, et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N Engl J Med. 2017; 376: 305-17.
  4. Zinplava® (bezlotoxumab) Australian approved product information. Macquarie Park: Merck Sharpe & Dohme. Approved August 2018.

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