Editing 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