Clostridium difficile causes antibiotic-
associated colitis
◦ fluoroquinolones, clindamycin, cephalosporins,
penicillins
◦ virtually all antibiotics, including metronidazole
and vancomycin
one of the most common healthcare-
associated infections
significant cause of morbidity and mortality
among elderly hospitalized patients
CLINICAL PICTURE
Wide spectrum of manifestations:
Asymptomatic carrier
20 % of hospitalized adults!
Symptomatic colitis
◦ CDAD / pseudomembranous colitis
◦ Watery diarrhea up to 10 or 15 times daily
◦ lower abdominal pain and cramping
◦ fever
◦ leukocytosis
Severe fulminant disease,
toxic megacolon
Pathogenesis of Clostridium difficile-
Associated Disease
DIAGNOSIS
The diagnosis of C. difficile infection
requires:
moderate to severe diarrhea or ileus, and
either:
A stool test positive for C. difficile or
Endoscopic or histologic findings of
pseudomembranous colitis
DIAGNOSIS
CLINICAL PICTURE +
◦ loose, watery, or semi-formed stools, three or
more (10-15), especially nocturnal +/- fever/ ileus
◦ during antibiotic therapy/ or 5 to 10 days
following antibiotic administration/ Infrequently,
10 weeks after cessation of therapy
◦ BIOLOGICAL TESTS
◦ ENDOSCOPY
◦ HISTOLOGY DATA
BIOLOGICAL TESTS
C. difficile toxin(s) or toxigenic C.
difficile organism
Polymerase chain reaction (PCR)
Enzyme immunoassay (EIA) for C. difficile
glutamate dehydrogenase (GDH)
Enzyme immunoassay (EIA) for C. difficile
toxins A and B
Cell culture cytotoxicity assay
Selective anaerobic culture
! C. Difficile toxin degrades at room temperature;
storage at 4ºC
PCR testing
Test for gene toxin
highly sensitive and specific
PCR results can be available within one
hour
potential for false positive results:
algorithm together with other assays
EIA for C. difficile GDH
GDH antigen is an essential enzyme
produced constitutively by all C. difficile
isolates
its detection cannot distinguish between
toxigenic and nontoxigenic strains
initial screening step in a multistep
approach (subsequent PCR testing)
highly sensitive
results are available in less than one hour
EIA for C. difficile toxins A and B
Most C. difficile strains produce both toxins
A and B; some strains produce toxin A or B
only
sensitivity 75%
high specificity (up to 99%)
relatively high false negative rate (100 to
1000 pg of toxin) must be present
inexpensive assays are commercially available
test results are available within several hours
Cell culture cytotoxicity assay
‘gold standard’ test
adding a prepared stool sample (diluted,
buffered, and filtered) to a monolayer of
cultured cells: cytopathic effect
characterized by rounding of fibroblasts in
tissue culture
more sensitive than enzyme
immunoassays
labor intensive and takes approximately
two days
Selective anaerobic culture
the most sensitive diagnostic method,
although it cannot distinguish toxin-
producing strains from non-toxin producing
strains
useful for epidemiologic studies
too slow
labor-intensive for clinical use
ENDOSCOPY
not warranted in patients with classic clinical
findings and a positive stool toxin assay
High clinical suspicion for C. difficile with
negative laboratory assay(s)
Prompt C. difficile diagnosis needed before
laboratory results can be obtained
Failure of C. difficile infection to respond
to antibiotic therapy
Atypical presentation with ileus or
minimal diarrhea
ENDOSCOPY
Pseudomembranes are sufficient to
make a presumptive diagnosis
raised yellow or white plaques up to 2 cm
in diameter, overlying an erythematous
and edematous mucosa
ENDOSCOPY - LIMITS
pseudomembranes are not observed in 10 to 20
% of cases
rarely seen in patients with inflammatory bowel
disease and superimposed C. difficile infection
In the setting of fulminant colitis - risk of
perforation.
may be absent in the rectosigmoid area but
visualized more proximally with colonoscopy
Endoscopy may be normal in patients with mild
disease or may demonstrate nonspecific colitis in
moderate cases.
HISTOPATHOLOGY
Type 1 - the mildest form,
pseudomembranes present, superficial
epithelium and lamina propria, crypt
abscesses are occasionally present.
Type 2 - more severe disruption of glands,
marked mucin secretion, more intense
inflammation of basal lamina.
Type 3 - severe, intense necrosis of the full
thickness of the mucosa with confluent
pseudomembranes (fibrinous material
containing polymorphonuclear cells)
IMAGING
Abdominal computed tomography (CT)
scan demonstrates pronounced thickening
of the colonic wall
CLINICAL APPROACH
Clinical suspicion:
◦ polymerase chain reaction (PCR)
either alone or as part of an algorithm (including
initial enzyme immunoassay [EIA] screening for
glutamate dehydrogenase [GDH], with or without
EIA screening for toxins A and B)
Colonoscopy not warranted if test +
DIFFERENTIAL DIAGNOSIS
Other infectious causes:
◦ Staphylococcus aureus
◦ Klebsiella oxytoca
◦ Clostridium perfringens
◦ Candida spp
◦ Salmonella
Noninfectious causes: osmotic diarrhea
◦ Cessation of symptoms with discontinuation of
oral intake
◦ Fever, leuckocytosis - absent
FULMINANT COLITIS
lower quadrant or diffuse abdominal pain,
diarrhea, abdominal distention, fever,
hypovolemia
lactic acidosis, hypoalbuminemia, marked
leukocytosis (up to 40,000 white blood
cells/microL or higher)
COMPLICATIONS
Toxic megacolon : colonic dilatation (>7 cm)
and severe systemic toxicity
Perforation:
◦ abdominal rigidity,
◦ involuntary guarding,
◦ diminished bowel sounds,
◦ rebound tenderness,
◦ severe localized tenderness
(left or right lower quadrants)
