 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)