Clostridium difficile associated diarrhoea (CDAD)

Last edited 08/2022 and last reviewed 09/2022

Pseudomembranous colitis is a very severe form of antibiotic associated colitis or diarrhoea. It is usually the result of the toxin of Clostridium difficile.

Most cases are hospital-acquired. Infection is faeco-oral, for example, via the patient's or staff's hands from a contaminated commode or equipment - rectal thermometer, sigmoidoscope, etc. Sixty percent of cases occur in the elderly.

Cause:

• Clostridium difficile toxins (A and B)

Reservoir:

• Human gastrointestinal tract
• Spores may be present on environmental surfaces contaminated by symptomatic persons

Transmission:

• person-to-person spread from symptomatic patients either directly or indirectly via contaminated hands of healthcare/other care workers
• via contact with environmentally contaminated surfaces e.g. commodes
• spread does not occur from asymptomatic carriers (1)

Incubation period:

• difficult to establish incubation period
• among patients commencing antibiotics, diarrhoea usually starts within 1-2 days of commencing antibiotics but can occur several weeks after antibiotic treatment

Infectivity:

• Most infectious when symptomatic
• Infectiousness reduces with treatment and decreasing severity of symptoms
• Stopping the implicated antibiotics (if possible) may be indicated

Referral criteria:

• refer people in the community with suspected or confirmed C. difficile infection to hospital if they are severely unwell, or their symptoms or signs worsen rapidly or significantly at any time. Refer urgently if the person has a life-threatening infection
  
  
• consider referring people in the community to hospital if they could be at high risk of complications or recurrence because of individual factors such as age, frailty or comorbidities
  
  
• ensure that people in hospital with suspected or confirmed C. difficile infection have care from a multidisciplinary team that may include a microbiologist, infectious diseases specialist, gastroenterologist, surgeon, pharmacist or dietitian, as needed.

Choice of antibiotic (2):

• when prescribing antibiotics for suspected or confirmed C. difficile infection in adults, follow table below
• when prescribing antibiotics forsuspected or confirmed C. difficile infection in children and young people under 18 years, base the choice of antibiotic on what is recommended for C. difficile infection in adults. Take into account licensed indications for children and young people, and what products are available (see the BNF for Children for dosing information)
• use clinical judgement to determine whether antibiotic treatment for C. difficile is ineffective. It is not usually possible to determine this until day 7 because diarrhoea may take 1 to 2 weeks to resolve
• Table Antibiotics for adults aged 18 years and over

  Treatment	Antibiotic, dosage and course length
  First-line antibiotic for a first episode of mild, moderate or severe C. difficile infection	Vancomycin: 125 mg orally four times a day for 10 days
  Second-line antibiotic for a first episode of mild, moderate or severe C. difficile infection if vancomycin is ineffective	Fidaxomicin: 200 mg orally twice a day for 10 days
  Antibiotics for C. difficile infection if first- and second-line antibiotics are ineffective	Seek specialist advice. Specialists may initially offer: Vancomycin: Up to 500 mg orally four times a day for 10 days With or without Metronidazole: 500 mg intravenously three times a day for 10 days
  Antibiotic for a further episode of C. difficile infection within 12 weeks of symptom resolution - relapse*	Fidaxomicin: 200 mg orally twice a day for 10 days
  Antibiotics for a further episode of C. difficile infection more than 12 weeks after symptom resolution - recurrence*	Vancomycin: 125 mg orally four times a day for 10 days Or Fidaxomicin: 200 mg orally twice a day for 10 days
  Antibiotics for life-threatening C. difficile infection	Seek urgent specialist advice, which may include surgery. Antibiotics that specialists may initially offer are: Vancomycin: 500 mg orally four times a day for 10 days With Metronidazole: 500 mg intravenously three times a day for 10 days

• * further episode (relapse or recurrence) of C. difficile infection
  • a further episode of C. difficile infection could either be a relapse, which is more likely to be with the same C. difficile strain, or a recurrence, which is more likely to be with a different C. difficile strain
  • was agreed that a relapse occurs within 12 weeks of previous symptom resolution and recurrence occurs more than 12 weeks after previous symptom resolution
• severity of C. difficile infection
  • mild infection:
    • not associated with an increased white cell count (WCC). Typically associated with fewer than 3 episodes of loose stools (defined as loose enough to take the shape of the container used to sample them) per day
  • moderate infection:
    • associated with an increased WCC (but less than 15 × 109 per litre). Typically associated with 3 to 5 loose stools per day
  • severe infection:
    • associated with a WCC greater than 15 × 109 per litre, or an acutely increased serum creatinine concentration (greater than 50% increase above baseline), or a temperature higher than 38.5 degrees Celsius, or evidence of severe colitis (abdominal or radiological signs)
    • number of stools may be a less reliable indicator of severity
  • life-threatening infection: symptoms and signs include hypotension, partial or complete ileus, toxic megacolon or CT evidence of severe disease
• prescribing notes:
  • see the BNF for appropriate use and dosing in specific populations, for example, hepatic impairment, renal impairment, pregnancy and breastfeeding. Also see medicines safety
  • see Specialist Pharmacy Service guidance on choosing between oral vancomycin options. If ileus is present, specialists may use vancomycin rectally

Notes:

• C. difficile spores are hardy and may remain on environmental surfaces for many weeks. Thorough environmental cleaning with suitable agents e.g. chlorine containing products is required to reduce transmission
• a review (3) noted that:
  • oral metronidazole appears acceptable for the treatment of a first episode of C. difficile
  • patients with persistent diarrhoea after 48 hours of appropriate anti-Clostridiodes therapy should be addressed to specialist

Reference:

• PHE (2019). Recommendations for the Public Health Management of Gastrointestinal Infections
• NICE (July 23rd 2021). Clostridioides difficile infection: antimicrobial prescribing
• Klezovich-Bénard M, Bouchand F, Rouveix E, Goossens PL, Davido B. Management and characteristics of patients suffering from Clostridiodes difficile infection in primary care. Eur J Gen Pract. 2021;27(1):320-325. doi:10.1080/13814788.2021.1998447