Clostridioides Difficile Infection
NICE guideline [NG199] Clostridioides difficile infection: antimicrobial prescribing. Published: Jul 2021.
UK Health Security Agency and Department of Health and Social Care Guidance Clostridioides difficile infection: how to deal with the problem. Last updated: Oct 2024.
Changes made:
- Background information added accordingly
- A section on isolation and prevention of spread has been added in the management section
Date: 25/11/25
Also known as: Clostridium difficile (C. difficile)
Background Information
Aetiology
Clostridioides difficile is an anaerobic, spore-forming, gram +ve bacillus (rod).
There are 2 strains of Clostridiodes difficile
- Only toxigenic strains cause C. difficile infection
- Non-toxigenic strains cause C. difficile colonisation, which is asymptomatic
Risk Factors
Primary route of transmission: spore-mediated faecal-oral
Risk factors: [Ref]
- Recent antibiotic exposure (within 3 months) – most important
- Cephalosporins, clindamycin, fluoroquinolones and penicillin with beta-lactamase inhibitors carry the highest risk
- Antibiotics disrupt normal gut flora, allowing C. difficile overgrowth
- Use of PPIs (e.g. omeprazole)
- Hospitalisation
- Contact with healthcare facility
- Advanced age
- Immunosuppression
- IBD (esp. ulcerative colitis)
- Recent GI surgery
- Presence of comorbidities (e.g. CKD, cardiac disease, liver disease)
Diagnosis
Clinical Features
Clinical presentation of C. difficile infection is very heterogeneous: [Ref1][Ref2]
- Profuse watery diarrhoea (≥3 loose stools in 24 hours without an alternative explanation) – most common presentation
- Abdominal pain / cramping
- Low-grade fever
The classic stereotypical presentation of C. difficle infection is a patient who develops watery diarrhoea after recent hospitalisation for an infection / antibiotic course.
Fulminant C. difficile infection is characterised by: [Ref1][Ref2]
- Toxic megacolon (→ severe abdominal distension)
- Ileus
- Multiple organ dysfunction
Investigation and Diagnosis
Confirmatory Test
Test of choice: stool sample for C. difficile toxin
- Diagnosis of C. difficle infection can be made if there is +ve C. difficile toxin + diarrhoea
Note that a +ve C. difficile antigen test CANNOT reliably diagnose C. difficile infection
- The antigen test detects the presence of glutamate dehydrogenase, which is found in all C. difficile bacteria, both toxigenic and non-toxigenic strains
- Remember, only toxigenic strains cause C. difficile infection, non-toxigenic strains cause asymptomatic C. difficile colonisation
A +ve C. difficile antigen test only confirms the presence of C. difficile bacteria, it does NOT distinguish between an active infection and asymptomatic colonisation. (C. difficile colonisation does NOT need treatment)
Other Tests
Key other tests: [Ref]
| Laboratory studies |
|
| Colonoscopy findings |
Colonoscopy should generally be avoided in patients with severe Clostridioides difficile infection due to the risk of perforation and lack of impact on management |
| Imaging | Imaging is useful to detect complications:
|
Management
Medication Review
Review any existing antibiotic treatment
- Stop the antibiotic, unless essential (e.g. serious ongoing infection)
- If an antibiotic is essential → switch to an alternative antibiotic with a lower risk of causing C. difficile infection
Review the need and consider stopping other medications:
- PPIs (continue only if necessary)
- Medications with GI activity or adverse effects
- Medications that may be problematic if the person is dehydrated (e.g. NSAIDs, ACE inhibitors, diuretics)
Prevention of Spread
Isolation rules:
- Patient should be isolated in a single room with a self-contained toilet and its own hand basin
- The patient should remain isolated until there has been no diarrhoea (types 5–7 on the Bristol Stool Chart) for at least 48 hours, and a formed stool has been achieved (types 1–4)
Infection control rules:
- All healthcare workers should wash their hands with soap and water before and
after contact with patients
body fluids- DO NOT use alcohol handrub as an alternative to soap and water
- All healthcare workers must use disposable gloves and aprons for any physical contact with patients
Hand hygiene must be performed with soap and water after patient contact, as alcohol-based hand rubs do not remove C. difficile spores effectively.
Antibiotic Treatment
Patients with confirmed C. difficile infection require antibiotic treatment. The choice of antibiotics depends on 1) severity and 2) whether it is a first or recurrent episode
| Severity | Features |
|---|---|
| Mild |
|
| Moderate |
|
| Severe |
|
| Life-threatening | Any of the following
|
Life-Threatening Infection
- Oral vancomycin + IV metronidazole
- Seek urgent specialist advice, which may include surgery
Non-Life-Threatening Infection
| Type of infection | Recommended antibiotic |
|---|---|
| 1st episode |
|
| Further episodes |
|
Consider a faecal microbiota transplant in adults with ≥2 previous episodes
Do not offer the following:
- During acute episodes: loperamide or other anti-motility medications (+ discontinue if C. diff develops)
- Reduced GI motility can promote toxin retention and increase the risk of toxic megacolon
- Bezlotoxumab (not cost-effective) / antibiotics / prebiotics or probiotics to prevent C. diff