Clostridium difficile

A common inhabitant of the GIT that can manifest in a spectrum of symptoms ranging from asymptomatic carrier to fulminant colitis.

Epidemiology

The most common cause of healthcare-associated diarrhoea
Prevalence of asymptomatic carriers amongst hospitalised patients is 3-26%

Risk factors

Recent antibiotics
- Decreases bowel flora, which allows C. diff to overrun
- Virtually all antibiotics have been implicated, but third and fourth generation cephalosporins, fluoroquinolones, clindamycin and carbapenems are the worst
Immunodeficiency
Chemotherapy
PPIs
GIT surgery or feeds
Prolonged hospitalisation or institutionalisation
IBD

Pathophysiology

Bacteriology
- Anaerobic, gram positive, spore-forming bacillus
- Transmitted person-to-person through faecal-oral route, or via contaminated hands/environment
- Clinical manifestations due to toxins
  - Produces toxins A (enterotoxin) and B (cytotoxin) - disrupt colonocyte cytoskeleton, alter cell function, disrupt tight junctions, kills colonocytes
  - Leads to oedema, inflammatory response, and subsequent pseudomembrane formation (formed from bacteria, fibrin, mucus and neutrophils)
  - Virulence of strains varies dramatically - the amount of toxin produced varies substantially. Ribotype 027 strain caused a large outbreak in mid-2000s.
Asymptomatic carriers also facilitate disease spread (faecal-oral route)
Pathophysiology of overgrowth/infection
- Antibiotic therapy disrupts colonic microflora
- C diff exposure and colonisation
- Release of toxins A and B
- Mucosal injury and inflammation

Presentations

Symptoms usually begin 4-9 days after initiation of antibiotics, but can commence up to 10 weeks later
New-onset, unexplained, watery diarrhoea
Can have abdominal pain, fever and ileus
Very high WCC in the context of colitis is most often CDI
Can be limited to right colonic disease in about 30% of cases
Enteritis can develop - especially patients with ileal pouch

Diagnosis

Stool testing
- Toxin-based
- Antigen-based
- Bacteria-based
  - Culture
  - PCR
- Tests generally remain positive for at least a month
Imaging
- Non-specific
- Pseudomembranes can be seen on USS
Sigmoidoscopy
- Can help differentiate equivocal cases
- Raised, yellowish-white small plaques (pseudomembranes) are seen in about 50% of patients with CDI
Colonoscopy
- Be very careful - risk of perforation
- Multiple circular plaque-like lesions, with a halo of erythema and loss of vascular pattern
- Pseudomembranes:
Histology
- Inflammatory exudate with mucinous debris, fibrin, necrotic epithelial cells, and polymorphonuclear cells

Severity

Asymptomatic carrier
Non-severe
Severe
- Leucocytosis, severe pain, AKI, high lactate, low albumin, high fever, organ dysfunction
Fulminant
- Hypotension
- Ileus (of colon)
- Megacolon
Can use ATLAS score to predict response to therapy (clinical cure at end of medical therapy) and mortality
Refractory disease: no improvement after 4 days of first-line therapy
Recurrence: recurrent symptoms after return to normal bowel movements, within two months of index infection

Medical treatment

Simple

- Stop offending antibiotic if possible
- IVF resuscitation - often necessary
- Correct electrolytes
- Avoid anti-peristaltic agents
- Hand hygiene with soap and water
- Avoid PPIs
- Infection control practices

Antibiotics (from eTG 24/5/23)

- First episode mild/moderate - PO metronidazole 400mg TDS for 10 days OR PO vancomycin 125mg QID for 10 days
  - Metronidazole can be given IV if necessary
  - Similar efficacy, but metronidazole should be first-line unless contraindicated for stewardship reasons
- First recurrence or refractory disease: vancomycin 125mg PO QID for 10 days OR fidaxomicin 200mg PO BD for 10 days
- Second and subsequent recurrence, or ongoing refractory disease:
  - Faecal microbiota transplant through nasoduodenal tube (success rate 91%)
  - Vancomycin PO 125mg QID for 14 days OR fidaxomicin 200mg PO BD for 10 days
- Severe disease: PO vancomycin 125mg QID for 10 days AND PO metronidazole 500mg TDS IV for 10 days. Consider also adding vancomycin 500mg via rectal tube q6h, mixed in 100mL saline
  - Consider adding tigecycline

Monoclonal antibodies

- Directed against toxins A (actoxumab) and B (bezlotoxumab)
- Neutralise toxin and limit colonic damage
- Probably makes a small difference

Surgery

See 'toxic megacolon' topic
Mortality is poor once shock develops - best to operate early if the patient is worsening on best medical therapy
Indications
- Absolute
  - Peritonitis or worsening abdominal exam
  - Perforation
  - Worsening end-organ failure, including intubation and vasopressor requirement after resuscitation
  - Abdominal compartment syndrome
  - Shock
  - Mental status changes
- Relative
  - WCC > 50
  - Lactate >5 after resuscitation
  - Clinical deterioration
Operation will be subtotal colectomy with end ileostomy
- The length of rectal stump retained is up to the surgeon - balance improved source control with improved chance of reversal and quality of life
- Typically would divide colon at the rectosigmoid junction, leaving the intra-abdominal rectum
- Don't do a segmental resection - take the whole colon
- Stoma marked prior
- The colon may be thickened, but is generally quite bland in appearance from the outside - don't be deterred from completing the full operation
Recent suggestions - loop ileostomy with colonic PEG irrigation followed by vancomycin irrigation
- Explore the abdomen to exclude perforation/necrosis, then bring out a loop ileostomy with a large IDC placed in the efferent limb and balloon inflated below the fascia (doesn't need to be across the ICJ). A rectal tube is placed at the anus. This can all be done laparoscopically. Then put 8L of warmed PEG through the colon. Then give vancomycin flushes TDS for a week, along with usual therapy.
- May give better mortality results than total colectomy (17% mortality vs 39% with total colectomy)
- Easier to reverse, good reversal rate
- No clear superiority according to UTD