Clostridioides difficile-associated disease

Key NICE recommendations on management

Please be aware that some of the following indications for medications may not be licensed by the manufacturer (i.e., the use of the medication is ‘off-label’). Refer to the full NICE guideline and your local drug formulary for further information when prescribing.

This summary covers antimicrobial prescribing recommendations for Clostridioides difficile (C. difficile) infection in adults, young people and children aged 72 hours and over.

Managing suspected or confirmed C. difficile infection

Assess the following in people with suspected or confirmed C. difficile infection:

• Whether it is a first or further episode (with the latter split into relapse or recurrence)

  • Relapse: an episode occurring within 12 weeks of previous symptom resolution (more likely to be infection with the same C. difficile strain)

  • Recurrence: an episode occurring >12 weeks after previous symptom resolution (more likely to be infection with a different C. difficile strain)

• The severity of the infection, defined (by Public Health England, 2013) as:

  • Mild: not associated with an increased white cell count; typically associated with fewer than 3 episodes of loose stools (defined as loose enough to take the shape of the sample container) per day

  • Moderate: associated with an increased white cell count (but <15 × 10⁹ per litre); typically associated with 3 to 5 loose stools per day

  • Severe: associated with a white cell count >15 × 10⁹ per litre, or an acutely increased serum creatinine concentration (>50% increase above baseline), or a temperature >38.5 ℃, or evidence of severe colitis (abdominal or radiological signs); number of stools may be a less reliable severity indicator

  • Life-threatening: symptoms and signs include hypotension, partial or complete ileus, toxic megacolon or CT evidence of severe disease

• Individual factors (e.g., age, frailty, comorbidities) that may affect the risk of complications or recurrence.

Refer people 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 they have a life-threatening infection; these people require urgent specialist advice, which may include surgery.

• Those in hospital should have care from a multidisciplinary team.

Consider referring people to hospital if they could be at high risk of complications or recurrence because of individual factors (e.g., age, frailty, comorbidities).

Stop any existing antibiotic treatment unless it is essential. If an antibiotic is still essential, consider changing to one with a lower risk of causing C. difficile infection.

Review the need to continue any treatment with:

• Proton-pump inhibitors and other medicines with gastrointestinal activity or adverse effects (e.g., laxatives)

• Medicines that may cause problems if the person is dehydrated (e.g., non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin-2 receptor antagonists, diuretics).

Offer adults with suspected or confirmed C. difficile infection an appropriate oral antibiotic.

• In the community, consider seeking prompt specialist advice from a microbiologist or infectious diseases specialist before starting treatment.

Use this guidance when choosing antibiotics for suspected or confirmed C. difficile in adults:

• For life-threatening infection, seek urgent specialist advice

  • Specialists may initially offer high-dose oral vancomycin with intravenous metronidazole for 10 days. They may use vancomycin rectally if there is ileus

• For a first episode of mild, moderate or severe infection:

  • Prescribe a 10-day course of low-dose oral vancomycin first-line

  • If vancomycin is ineffective, prescribe a 10-day course of oral fidaxomicin second-line

    • Use clinical judgement to determine if antibiotic treatment is ineffective (it is not usually possible to determine this until day 7 as diarrhoea may take 1 to 2 weeks to resolve)

• If first-line and second-line antibiotics are ineffective, seek specialist advice

  • Specialists may initially offer high-dose oral vancomycin with or without intravenous metronidazole for 10 days

• For a further episode (i.e., not the first episode), prescribe a 10-day course of:

  • Oral fidaxomicin to treat a relapse

  • Oral low-dose vancomycin or oral fidaxomicin to treat a recurrence.

Children and young people (under 18 years) with suspected or confirmed C. difficile infection should be offered an oral antibiotic. Treatment should only be started by, or after advice from, a microbiologist or an appropriate paediatric specialist.

• The choice of antibiotic should be based on what is recommended above for adults.

For people who cannot take oral medicines, seek specialist advice about alternative enteral routes for antibiotics (e.g., nasogastric tube or rectal catheter).

Manage fluid loss and symptoms as you would for acute gastroenteritis.

Faecal microbiota transplantation should be considered for a recurrent episode of C. difficile infection in adults who have had 2 or more previous episodes.

Do not offer antimotility medicines such as loperamide (these slow gut action, potentially leading to C. difficile toxins being retained longer, which may make the person more unwell).

Reassess people if symptoms or signs do not improve as expected, or worsen rapidly or significantly at any time. Daily review may be needed (e.g., if the person is in hospital).

Consider stopping antibiotics started for suspected C. difficile infection if subsequent stool sample tests do not confirm C. difficile infection.

Patient advice

Advise people with suspected or confirmed C. difficile infection about:

• Drinking enough fluids to avoid dehydration

• Preventing the spread of infection (e.g., hygiene measures)

• Seeking medical help if symptoms worsen rapidly or significantly at any time.

Prevention of C. difficile infection

Record any diagnosis of C. difficile infection appropriately so that it can be considered before any future antibiotics are prescribed.

Do not:

• Offer antibiotics to prevent C. difficile infection

• Offer bezlotoxumab to prevent infection recurrence (as it is not cost-effective)

• Advise people taking antibiotics to take prebiotics or probiotics to prevent C. difficile infection.

See the NICE guideline for more information on prevention of C. difficile infection (including good antimicrobial stewardship, infection control and environmental hygiene measures).

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