Introduction and current guidance

Introduction and current guidance

Clostridium difficile are bacteria that exist in the environment and can become established in the colon of healthy people (up to 3% of adults and 66% of babies). C difficile infection occurs when the other harmless bacteria in the colon are disrupted (for example, by taking antibiotics) or when the immune system is compromised, allowing the numbers of C difficile bacteria to increase to high levels. Certain strains of C difficile produce toxins (principally A and B) that damage the lining of the colon, causing symptoms ranging from mild, self-limiting diarrhoea to pseudomembranous colitis, toxic megacolon, perforation of the colon, sepsis and death. Type 027 is a strain that produces more toxins than most other types of C difficile. It causes a greater proportion of severe disease and appears to have a higher mortality (NICE clinical knowledge summary: diarrhoea – antibiotic associated; Public Health England, Clostridium difficile: guidance, data and analysis; Public Health England, Clostridium difficile infection: how to deal with the problem).

As well as broad-spectrum antibiotics, other factors increase the risk of C difficile infection. These include advanced age, underlying morbidity, hospitalisation, exposure to other people with the infection, long duration of antibiotic treatment, taking multiple antibiotics concurrently or taking multiple antibiotic courses, and inflammatory bowel disease. In hospitalised people, the rate of recurrence is around 20% after a first episode and 45–60% after a second episode of C difficile infection. The mortality rate of C difficile infection can be up to 25% in frail, elderly people in hospitals (NICE clinical knowledge summary: diarrhoea – antibiotic associated).

Public Health England's guidance on managing common infections in primary care recommends metronidazole (400 mg or 500 mg 3 times daily for 10–14 days) first-line for treating first episodes of mild to moderate C difficile infection. Vancomycin (125 mg 4 times daily for 10–14 days) is an option for second episodes, or if the infection is severe (raised temperature or white cell count, rising creatinine, or signs or symptoms of severe colitis) or caused by the type 027 strain of C difficile. If infection recurs, vancomycin or fidaxomicin (200 mg twice daily for 10 days) may be used.

This is based on Public Health England's updated guidance on the management and treatment of C difficile infection, which includes more information on the assessment and treatment of C difficile infection, including a summary of the evidence base and 2 treatment algorithms. It also gives more detail on managing recurrent infection, advising that fidaxomicin should be preferred for people with recurrent C difficile infection, but that the efficacy of fidaxomicin in people with multiple C difficile infection recurrences is unclear. Depending on local cost-effectiveness based decision making, oral vancomycin is an alternative.

This evidence summary considers the evidence to support the use of a new medicine, bezlotoxumab, which is the first medicine that is indicated for preventing the recurrence of C difficile, rather than treating the infection.