CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA

Pseudomembranous Colitis
Dr.T.V.Rao MD

Dr.T.V.Rao MD 1
 Clostridium difficile
• Clostridium difficle (Greek cluster
spindle, and Latin difficle difficult), is
a species of Gram-positive bacteria
of the genus Clostridium that causes
diarrhea and other intestinal disease
when competing bacteria are wiped
out by antibiotics.
Dr.T.V.Rao MD 2
 Introduction
• Clostridium difficle is a Gram-positive,
spore-forming anaerobic bacillus.
• Most common cause of nosocomial
diarrhea.
• Rate and severity of C. difficle-associated
diarrhea (CDAD) increasing.
• New strain of C.difficile with increased
resistance and virulence identified.
Dr.T.V.Rao MD 3
 History
• 1893 – first case of pseudomembranous
colitis reported as diphtheritic colitis.
• 1935 – “Bacillus difficle” isolated.
• 1970s – antibiotic-asociated colitis identified.
• 1978 – C. difficle toxins identified in humans.
• 1979 – therapy with Vancomycin or
metronidazole
• 2000 – increased incidence and virulence
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 Recent Developments
• C difficle first described 1935 gram-positive anaerobic
bacillus
• “difficult clostridium”-difficult to grow in culture
• Found in stool specimens from healthy neonates leading
to misclassification as a commensal organism
• 1970s: “clindamycin colitis” pseudomembranous colitis in
hospitalized patients
• 1978: C diffficle recognized as causative organism

Dr.T.V.Rao MD 5
 Introduction
• Clostridium difficile is a Gram-
positive, spore-forming anaerobic
bacillus.
• Most common cause of nosocomial
diarrhea.
• Rate and severity of C. difficile-associated
diarrhea (CDAD) increasing.
• New strain of C.difficile with increased
resistance and virulence identified.
Dr.T.V.Rao MD 6
 C.difficile
• Clostridium difficile, often
called C. difficile or "C. diff,"
is a bacterium that can
cause symptoms ranging
from diarrhea to life-
threatening inflammation of
the colon. Illness from C.
difficile most commonly
affects older adults in
hospitals or in long term
care facilities and typically
occurs after use of
antibiotic medication

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 Epidemiology
• Present in environment.
• Hospital is major reservoir. Spores can be
recovered from surfaces for months.
• Spread primarily on hands of HCW.
• Fecal-oral transmission.
• Transmission may occur from
asymptomatic colonized persons.

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 Epidemiology
• Colonizes the colon of up to 3% of healthy
adults.
• 15 – 25% of debilitated and antibiotic-treated
hospitalized adults colonized.
• Toxigenic strains may cause disease in
colonized patients.
• Implicated in approx. 25% of cases of
antibiotic- associated diarrhea

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 The antibiotics most likely to
cause diarrhea
• Cephalosporins, such as cefixime (Suprax) and
cefpodoxime (Vantin)
• Clindamycin (Cleocin)
• Erythromycin (Erythrocin, E.E.S., others)
• Penicillins, such as amoxicillin
(Larotid, Moxatag, others) and ampicillin
• Quinolones, such as ciprofloxacin (Cipro) and
levofloxacin (Levaquin)
• Tetracyclines, such as doxycycline
(Vibramycin, Periostat, others) and minocycline
(Minocin, Solodyn, others)

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 Other predisposing factors
• Previously experienced antibiotic-associated
diarrhea while taking an antibiotic medication
• Are age 65 or older
• Have had surgery on your intestinal tract
• Have recently stayed in a hospital or nursing
home
• Have a serious underlying illness affecting your
intestines, such as colon cancer or inflammatory
bowel disease

Dr.T.V.Rao MD 11
 Source of Infection
• C. difficle bacteria can be found throughout
the environment — in soil, air, water, and
human and animal feces. A small number of
healthy people naturally carry the bacteria in
their large intestine. But C. difficle is most
common in hospitals and other health care
facilities, where a much higher percentage of
people carry the bacteria.

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 Pathogenesis
• Disruption of normal
colonic flora
• Colonisation with C.
difficle
• Production of toxin A
+/- B
• Mucosal injury and
inflammation

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 Pathogenesis
• Microflora of gut:
– 1012 bacteria/gram
– 400-500 species
– colonisation resistance
• Transmission -
faecal/oral
– spores
• Late log / early
stationary phase
– toxin production

Dr.T.V.Rao MD 14
Disruption of protective
colonic flora (AB or AN)

Colonization with toxigenic C. difficle

by fecal-oral transmission

Toxin A and B production

A/B: Cytoskeletal damage, loss of tight junctions.

A: Mucosal injury, inflammation, fluid secretion.

Colitis and Diarrhea

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 Clinical features
• Mild disease – mild abdominal cramping pain.
- endoscopic findings of diffuse or
patchy, nonspecific colitis.
• Moderate disease – fever, dehydration, nausea,
anorexia, malaise, profuse
diarrhea, abdominal distention and cramping
pain.
- moderate leukocytosis, fecal
leukocytes.
- diffuse, patchy colitis on endoscopy

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 Clinical Manifestations
• Fulminant colitis:
– Rare, 2-3% of patients, esp elderly
– Serious: ileus, perforation, mega colon, death
– High fever, chills, marked leukocytosis (>40K)
– May not have diarrhea if ileus or mega colon
– Risk of perforation w/ sigmoid/colonoscopy
– Treatment surgical
• Unusual presentations:
– Long latency period (1-2months)
– Absence of antibiotic exposure

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Dr.T.V.Rao MD 18
 Severe disease
• Severe disease – usually profuse diarrhea, may
be little or no diarrhea.
- abdominal pain
- fever
- volume depletion
- marked leukocytosis
peritoneal signs - radiologic signs include
ileus, dilated colon and edematous colonic
mucosa - endoscopic findings of adherent
yellow plaques
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 Complications of CDAD
• Pseudomembranous
colitis
• Toxic mega colon
• Perforation of the
colon
• Sepsis
• Death
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 Patients at increased risk for disease
• ANTIBIOTIC EXPOSURE
• Gastrointestinal surgery or manipulation
• Long length of stay in healthcare setting
• Infected roommate
• Co-morbid illnesses
• Immunosuppression
• Advanced age
• Proton-pump inhibitors and H2-blockers?

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 Predictors of Severe Disease

• Leukocytosis
> 20,000
• Increased
creatinine
above the
baseline
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 Traditional list of Antibiotics associated with
CDAD
MORE FREQUENT LESS FREQUENT

Cephalosporins (3rd and 4th generation) Ticarcillin-clavulanate

Ampicillin/Amoxicillin Metronidazole

Clindamycin Fluoroquinolones

Other penicillins Rifampin

Macrolides 5-Fluorouracil

Tetracycline's Methotrexate

Trimethoprim-Sulphmethoxazole Cyclophosphamide
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 DIAGNOSIS
• Endoscopy (pseudomembranous
colitis)
• Culture
• Cell culture cytotoxins test
• ELISA toxin test
• PCR toxin gene detection
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 Laboratory Diagnosis
• Stool culture
• Latex agglutination to
detect antigen in stools
• Tissue culture assay for
cytotoxicity of toxin B
• Enzyme-linked Immuno-
Sorbant assay (ELISA)
for toxins A and B

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 A new strain of C. difficle (NAP-1)
• Toxin type III
• Unsuppressed production of toxins A and
B
• Associated with presence of binary
toxin.
• Increased resistance to clindamycin
and fluoroquinolones.
• Potential for increased complications
and adverse outcome.
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 Management
• Enhanced infection
control measures.
• Targeted antibiotic
restriction
• Appropriate antibiotic
therapy
• Adjunctive therapy –
probiotics, IVIG, toxin
binders

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Important supporting approaches
• Surgery
• Avoid ant peristaltic and opiate
drugs.
• Experimental therapy – rifaximin,
tolevamar, corticosteroids, vaccine,
monoclonal antibodies to toxins A
and B, non-toxigenic C,difficile
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 Antibiotic Therapy

• Oral therapy –
Vancomycin, metronidazole
• Unable to tolerate oral therapy – IV
metronidazole, Vancomycin via NG tube
or enema.
• Vancomycin + rifampin
• Less frequently used – Bacitracin, fluidic
acid
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 Indications for Vancomycin therapy
• No response to
metronidazole
• Metronidazole
intolerance
• Pregnancy and child
< 10 yrs.
• Severe/fulminant
CDAD

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CDAD continues to be a Important Topic in
Clinical Practice
• Increasing numbers and severity of
CDAD.
• Active surveillance recommended.
• Early diagnosis and treatment are
important for reducing severe outcome.
• Judicious use of antibiotics may reduce
incidence of CDAD
• Strict infection control practices
essential.
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• Programme created by Dr.T.V.Rao MD
for Medical and Health Care
Professionals in the Developing World
• Email
• doctortvrao@gmail.com

Dr.T.V.Rao MD 33