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Clostridium difficile associated diarrhea
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CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEAPseudomembranous 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
Dr.T.V.Rao MD 4
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
• 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
C.difficile
Dr.T.V.Rao MD 7
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.
Dr.T.V.Rao MD 8
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
Dr.T.V.Rao MD 9
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)
Dr.T.V.Rao MD 10
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.
Dr.T.V.Rao MD 12
Pathogenesis• Disruption of normal
colonic flora• Colonisation with C.
difficle• Production of toxin A
+/- B• Mucosal injury and
inflammation
Dr.T.V.Rao MD 13
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 protectivecolonic flora (AB or AN)
Colonization with toxigenic C. difficleby fecal-oral transmission
Toxin A and B production
A/B: Cytoskeletal damage, loss of tight junctions.A: Mucosal injury, inflammation, fluid secretion.
Colitis and DiarrheaDr.T.V.Rao MD 15
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
Dr.T.V.Rao MD 16
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
Dr.T.V.Rao MD 17
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
Dr.T.V.Rao MD 19
Complications of CDAD• Pseudomembranous
colitis• Toxic mega colon• Perforation of the
colon• Sepsis• Death
Dr.T.V.Rao MD 20
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?
Dr.T.V.Rao MD 21
Predictors of Severe Disease
• Leukocytosis > 20,000
• Increased creatinine above the baseline
Dr.T.V.Rao MD 22
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
Dr.T.V.Rao MD 23
DIAGNOSIS• Endoscopy (pseudomembranous
colitis)• Culture• Cell culture cytotoxins test• ELISA toxin test• PCR toxin gene detection
Dr.T.V.Rao MD 24
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
Dr.T.V.Rao MD 25
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.Dr.T.V.Rao MD 26
Management
• Enhanced infection control measures.
• Targeted antibiotic restriction
• Appropriate antibiotic therapy
• Adjunctive therapy – probiotics, IVIG, toxin binders
Dr.T.V.Rao MD 27
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
Dr.T.V.Rao MD 28
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
acidDr.T.V.Rao MD 29
Indications for Vancomycin therapy
• No response to metronidazole
• Metronidazole intolerance
• Pregnancy and child < 10 yrs.
• Severe/fulminant CDAD
Dr.T.V.Rao MD 31
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.Dr.T.V.Rao MD 32
• Programme created by Dr.T.V.Rao MD for Medical and Health Care
Professionals in the Developing World• Email
Dr.T.V.Rao MD 33
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