C-Diff Colitis

DEFINITION
C-Difficile colitis
D E A B M I M


EPIDEMIOLOGY

An increasing epidemic with a massive associated health cost burden.
Antibiotic usage - prevalent misuse and overuse.

Hospitalized pts are at risk

Risk Factors

Antibiotics
Cephalosporins, fluroquinolones and clindamycin
Multiple agents
ABs>7d
- (however, can occur with a single dose)
Patient factors
Age>65
Prolonged hospital stay; 13% colonization at 2 weeks, 50% at 4 weeks.
Comorbidities
Debilitated patients, hypoalbuminaemia
Transplanted pts, burns
GI surgery
PPIs

D E A B M I M
 

AETIOLOGY

Clostridium difficile
- increase in frequency and severity associated with aggressive strains, with resistance also developing.
- anaerobic gram +ve organism
Resident in 3% of general populations' colons but 10%+ of hosp pts (see above)

A highly resistant spore-forming bacteria
Common in environment: soil, swimming pools, tap water.
There are toxigenic and non-toxigenic isolates
- toxigenic c. diff usually has both A and B toxins.

Cultured in hospital from healthcare workers' shoes, fingernails, call buttons.
- lingers in rooms 40d after discharge
Hand washing is critical


D E A B M I M
 

BIOLOGICAL BEHAVIOUR

Pathophysiology

1. Ingestion and colonization of C. Diff
Commonly transmitted by fecal-oral route
Spores are resistant to gastric acid and linger in gut.

2. Loss of normal gut flora protective effect

Deplete carbon sources required for C. diff, prevent adherence, produce growth inhibitors
Wiped out by antibiotics, permitting C diff growth

3. Permissive host response
Serum and mucosal Ig should protect.
Pt factors enable C diff growth.

4. Toxin generation
A = enterotoxin, some cytotoxic properties
B = cytotoxin.  Disrupts intestinal epithelium, allowing fluid leakage.
Both stimulate inflammatory cascade
- proinflammatory cytokines: TNF-alpha, IL1, IL6, IL8, prostaglandin pathway
--> massive infiltration with neutrophils, macrophages, and lymphocytes.

Pathology

Form pseudomembranes (v. common in severe cases; <20% mild cases)
- makes up nearly 100% of pseudomembranous colitis cases
- formed of bacteria, fibrin, mucus and inflammatory cells.
Rectum may be spared.
D E A B M I M
 

MANIFESTATIONS

Commonly a week or so after exposure.

Broad spectrum
- from mild diarrhoea to severe colitis with perforation.
 
1. Mild self-limiting colitis
Diarrhoea
No systemic manifestations

2. Moderate colitis
Profuse diarrhoea
Distention and pain
SIRS and oliguria
Responsive to supportive measures

3. Fulminant colitis
As above, plus:
Bleeding (poss occult)
Critically unwell requiring ICU support, severe oliguria, pressors.
Diarrhoea may diminish as colonic muscles fail.
* Note may not have diarrhoea
* High degree of suspicion required --> CT

Sigmoidoscopy
/ Endoscopy
Ulceration and pseudomembranes.
Raised, yellowish, 2-10mm lesions, skip; coalesce to plaques in severe cases
Risk of perforation by procedure.

D E A B M I M


INVESTIGATIONS

May have marked leukocytosis.

Toxin detection

There are many possible tests.

1. My laboratory uses a faecal C-diff toxin nucleic acid detection test
- tests A and B toxins.
- high sensitivity and specificity

2. Most sensitive is toxin B detecting tissue culture
- but this takes 1-3d
- order this if in doubt

3. Stool culture high sensitivity and specificity
- but not often performed as labor intensive,  slow 3-4d

4. Rapid enzyme immunoassay for toxin A or B
- faster return time (a few hours), highly specific, but less sensitivity (~70-80%)
- <2% of c. diff produce only B so caution in toxin-A-only testing

5. Latex agglutination test

CT
Diffuse colon wall thickening and colonic dilation;
Possibly internal pseudomembrane.
Stranding, pneumotosis, free fluid, megacolon, perforation can indicate severity
D E A B M I M


MANAGEMENT

Treat mild-moderate disease, not asymptomatic colonization.
Supportive therapy.
- monitor for complications incl perforation.
Avoid anti-peristaltic agents.
Contact isolation
Cease antibiotics
- and avoid 2mo after infection resolution if possible.

1. Antibiotics

Oral metronidazole
- 400mg po tds
- IV 500 tds if unable to take po meds
- respond within 7 days; long courses not advisable as aggressive resistant strains emerge.
- often effective, however recent less-sensitive strains are concerning.
Vancomycin
- 125 mg qid
- when facing virulent organisms and severe disease
- often combination therapy with metronidazole
- consider intracolic vanc via retention ememas

Other points
Consult ID
Exclude resistant strain
Cholesyramine in refractor cases
Emerging role for fecal transplant
Emerging role for loop ileostomy and colonic antibiotic lavage as surgery-preventing step.

Surgery
Not commonly required <1% of all c. diff.
Often a difficult decision; high morbidity and mortality.
- mortality approaches 50% in ICU pt with WCC >30 and age >70...
- but worsened by delayed intervention

Indications

Perforation
Megacolon
Lack of response to therapy and ongoing organ failure, shock, vasopressors

Plan
Colon often distended, oedematous, grey, paper thin, sealed miniperforations.
Do a subtotal colectomy.
- rectum divided at peritoneal reflection
Need an expedient procedure.
Stoma essential.
- exteriorize ileum and Hartmann's pouch or mucus fistula the rectum.

Can restore continuity when well, remembering they are at risk from this disease again when closed and given ABs.

Relapse
Can occur in up to 20%
D E A B M I M


REFERENCES
Schein 3rd
Cameron 10th