Transcript Clostridium difficile Colitis

Clostridium difficile Colitis
C. diff.—Gram stain
Bacteriology
• anaerobic gram-positive, spore-forming, toxinproducing bacillus
• first described in 1935
• C. difficile can exist in spore and vegetative
forms.
• releases two potent exotoxins that mediate
colitis and diarrhea
– toxin A ("enterotoxin")
– toxin B ("cytotoxin")
Bacteriology
• Toxin A causes inflammation leading to
intestinal fluid secretion, mucosal injury and
inflammation
Bacteriology
• Toxin B is essential for the virulence of C.
difficile, and is approximately ten times more
potent than toxin for mediating colonic
mucosal damage
Epidemiology
• C. difficile colonizes the colon of about 2
percent of healthy adults.
• New colonization occurs predominantly by the
fecal-oral route.
• Patients who become colonized are
subsequently at risk for developing C. diff,
primarily after treatment with antibiotics.
Pathophysiology
• Colonization of the intestinal tract occurs via
the fecal-oral route.
• Facilitated by disruption of normal intestinal
flora due to antimicrobial therapy.
• The organism is capable of elaborating
exotoxins that bind to receptors on intestinal
epithelial cells, leading to inflammation and
diarrhea.
Pathophysiology
• Once intracellular, toxins A and B inactivate
regulatory pathways mediated by proteins
that are involved in cytoskeleton structure.
This leads to shallow ulceration on the
intestine mucosal surface.
• Both toxins also disrupt intercellular tight
junctions.
Pathophysiology
• Toxin B is essential for the virulence of C.
difficile, and is approximately ten times more
potent than toxin A in mediating colonic
mucosal damage.
• Strains lacking toxin A can be as virulent as
strains with both toxins.
Hypervirulent Strain
• A new, hypervirulent strain, NAP1/BI/027, has
been implicated as the responsible pathogen
in selected Clostridium difficile outbreaks
since the early 2000s.
• produces binary toxin related to the iota-toxin
found in Clostridium perfringens.
• produces substantially larger quantities of
toxins A and B in vitro than other C. difficile
strains.
Clinical Manifestations
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Watery diarrhea
Abdominal pain and cramping
Low grade fever
Leukocytosis
Ileus
Abdominal tenderness
Extra-colonic Manifestations
• Protein-losing enteropathy with ascites
• C. difficile infection in the setting of chronic
inflammatory bowel disease
• Extracolonic involvement
--appendicitis
--small bowel enteritis
--extraintestinal involvement—cellulitis,
arthritis
Diagnosis
• Anaerobic stool culture is the most sensitive
test—impractical.
• Toxin assays--EIA
– specificity (up to 99 percent)
– variable sensitivity (60 to 95 percent)
– relatively high false negative rate since 100 to
1000 pg of toxin must be present for the test to be
positive
Diagnosis
• Stool WBCs
– Sensitive—fecal leukocytes never normal
– Low specificity—but clinical setting will help
– Cheap
– Readily available
Diagnosis
• Sigmoidoscopy or colonoscopy—findings
variable.
• CT scan--not usually necessary
– Non-specific
– Expensive
– Radiation exposure
Treatment
• Initial episode: Preferred: metronidazole 500
mg orally three times daily or 250 mg four
times daily for 10 to 14 days.
• Alternative: vancomycin 125 mg orally four
times daily for 10 to 14 days First relapse
Confirm diagnosis (see text) If symptoms are
mild, conservative management may be
appropriate If antibiotics are needed, repeat
treatment as in initial episode
Treatment
• Up to 50 percent of patients have positive
stool assays for as long as six weeks after the
completion of therapy. DON’T repeat C. diff
toxin assay as routine.
Approach to Treatment Failure
• Recurrent disease often results from
reinfection with the same or a different strain
of C. difficile.
• Up to one-half of recurrent episodes are
reinfections rather than relapses of infection
with the original strain.
Treatment Failure
• Risk factors for recurrence
– age >65 years
– severe underlying medical disorders
– ongoing therapy with concomitant antibiotics
Treatment Failure
• First relapse:
– If symptoms are mild, conservative
management may be appropriate.
– If antibiotics are needed, repeat
treatment as in initial episode above
Treatment Failure
• Second relapse: Tapering and pulsed oral
vancomycin 125 mg orally four times daily for
7 to 14 days--125 mg orally twice daily for 7
days--125 mg orally once daily for 7 days--125
mg orally every other day for 7 days--125 mg
orally every 3 days for 14 days.
• Alternative: fidaxomicin 200 mg orally twice
daily for 10 days[4]
Treatment Failure
• Subsequent relapse: Vancomycin 125 mg
orally four times daily for 14 days, followed by
rifaximin 400 mg twice daily for 14 days.
• Alternative: Fidaxomicin 200 mg orally twice
daily for 10 days.
Fecal Infusion
• Cure rates are high (up to 100 percent in small
series), with a high level of patient
acceptance.
• However, there is a concern about
transmission of infectious agents to the stool
recipient.
Fecal Infusion
• 200 to 300 g of donor stool suspended in 200
to 300 mL of sterile normal saline
(homogenized briefly in kitchen blender to a
liquid consistency).
• Administered via enema or NG or NE tube
within 10 minutes of preparation, repeated
daily for five days.
• Can also be given as an enema or injected
thru a colonoscope.
Prevention--Goals
• Prevention of new colonization with the
organism
• Prevention of C. diff colitis among patients
already colonized by the organism
Prevention
• Surveillance — track rates of C. diff.
• Contact precautions — patients should be
placed on contact precautions, including
gloves and gowns.
• Hand hygiene — Alcohol-based hand rub
(ABHR) does NOT eradicate C. difficile spores.
Centers for Disease Control recommends soap
and water hand hygiene when caring for
patients with C. diff.
Prevention
• Stethoscope disinfection — alcohol wipes or
gauze moistened with sterile water or alcohol.
• Environmental cleaning—bleach solution.
• Restrict antibiotic usage—clindamycin,
fluroquinolones and cephalosporins
• Home hygiene—clean surfaces with dilute
bleach
Summary
• Clostridium difficile infection is one of the most
common hospital-acquired infections.
• Recurrences frequently caused by reinfection.
• Environmental hygiene is mandatory.
• Diagnosis and treatment need not be expensive.
• Antibiotic usage should be reduced.
• Pulse-taper therapy is effective for complicated
recurrence.
• Fecal infusion therapy useful in severe refractory
disease